https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Madelyn+SmithProteopedia - User contributions [en]2026-10-05T17:10:57ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=Noxafil&diff=2742877Noxafil2017-04-20T12:13:19Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>. It is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] (Posaconazole 2D Structure)<ref name=pubchem/><br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaced with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues enhance antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the fungal cytochrome P450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast, ''Candida albicans'', in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom, on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> , and an iron atom, on heme, located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is essential and performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, headaches, fever, vomiting, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals <ref name="formularyjournal"/>. <br />
It should be taken with food to help absorption and is generally taken 3 times a day in 200 mg doses. For fungi that have been unmanageable through other treatments, 800 mg are given 2 or 4 times a day to treat infection <ref name="greer"> Greer ND. Posaconazole (Noxafil): a new triazole antifungal agent. Proceedings (Baylor University Medical Center). 2007;20(2):188-196. PMID: PMC1849883 </ref><br />
<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Fungal resistance among these pathogens are becoming more frequent, requiring the development of new, more effective antifungal drugs. Noxafil oral suspension is the most effective form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections, particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Noxafil&diff=2742820Noxafil2017-04-20T05:29:39Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>. It is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] (Posaconazole 2D Structure)<ref name=pubchem/><br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaced with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues enhance antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the fungal cytochrome P450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast, ''Candida albicans'', in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom, on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> , and an iron atom, on heme, located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is essential and performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, headaches, fever, vomiting, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal). <br />
It should be taken with food to help absorption and is generally taken 3 times a day in 200 mg doses. For fungi that have been unmanageable through other treatments, 800 mg are given 2 or 4 times a day to treat infection <ref name="greer"> Greer ND. Posaconazole (Noxafil): a new triazole antifungal agent. Proceedings (Baylor University Medical Center). 2007;20(2):188-196. PMID: PMC1849883 </ref><br />
<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Fungal resistance among these pathogens are becoming more frequent, requiring the development of new, more effective antifungal drugs. Noxafil oral suspension is the most effective form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections, particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Noxafil&diff=2742792Noxafil2017-04-20T03:43:09Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>. It is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] (Posaconazole 2D Structure)<ref name=pubchem/><br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaced with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues enhance antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast, ''Candida albicans'', in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom, on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> , and an iron atom, on heme, located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is essential and performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, headaches, fever, vomiting, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal). <br />
It should be taken with food to help absorption and is generally taken 3 times a day in 200 mg doses. For fungi that have been unmanageable through other treatments, 800 mg are given 2 or 4 times a day to treat infection <ref name="greer"> Greer ND. Posaconazole (Noxafil): a new triazole antifungal agent. Proceedings (Baylor University Medical Center). 2007;20(2):188-196. PMID: PMC1849883 </ref><br />
<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Fungal resistance among these pathogens are becoming more frequent, requiring the development of new, more effective antifungal drugs. Noxafil oral suspension is the most effective form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections, particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Noxafil&diff=2742767Noxafil2017-04-20T02:41:54Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] (Posaconazole 2D Structure)<ref name=pubchem/><br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaced with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues enhance antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast ''Candida albicans'' in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is essential and performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, headaches, fever, vomiting, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal). <br />
It should be taken with food to help absorption and is generally taken 3 times a day in 200 mg doses. For fungi that have been unmanageable through other treatments, 800 mg are given daily 2 or 4 times a day to treat infection <ref name="greer"> Greer ND. Posaconazole (Noxafil): a new triazole antifungal agent. Proceedings (Baylor University Medical Center). 2007;20(2):188-196. PMID: PMC1849883 </ref><br />
<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Fungal resistance among these pathogens are becoming more frequent, requiring the development of new, more effective antifungal drugs. Noxafil oral suspension is the most effective form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Noxafil&diff=2742761Noxafil2017-04-20T02:31:53Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] (Posaconazole 2D Structure)<ref name=pubchem/><br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaced with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues enhance antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is essential and performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, headaches, fever, vomiting, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal). <br />
It should be taken with food to help absorption and is generally taken 3 times a day in 200 mg doses. For fungi that have been unmanageable through other treatments, 800 mg are given daily 2 or 4 times a day to treat infection <ref name="greer"> Greer ND. Posaconazole (Noxafil): a new triazole antifungal agent. Proceedings (Baylor University Medical Center). 2007;20(2):188-196. PMID: PMC1849883 </ref><br />
<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Fungal resistance among these pathogens are becoming more frequent, requiring the development of new, more effective antifungal drugs. Noxafil oral suspension is the most effective form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Noxafil&diff=2742751Noxafil2017-04-20T02:13:13Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaced with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues enhance antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is essential and performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, headaches, fever, vomiting, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal). <br />
It should be taken with food to help absorption and is generally taken 3 times a day in 200 mg doses. For fungi that have been unmanageable through other treatments, 800 mg are given daily 2 or 4 times a day to treat infection <ref name="greer"> Greer ND. Posaconazole (Noxafil): a new triazole antifungal agent. Proceedings (Baylor University Medical Center). 2007;20(2):188-196. PMID: PMC1849883 </ref><br />
<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Fungal resistance among these pathogens are becoming more frequent, requiring the development of new, more effective antifungal drugs. Noxafil oral suspension is the most effective form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Noxafil&diff=2742632Noxafil2017-04-19T21:57:51Z<p>Madelyn Smith: New page: <StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''> ==Introduction== Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2...</p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, headaches, fever, vomiting, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
It should be taken with food to help absorption and is generally taken 3 times a day in 200 mg doses. For fungi that have been unmanageable through other treatments, 800 mg are given daily 2 or 4 times a day to treat infection <ref name="greer"> Greer ND. Posaconazole (Noxafil): a new triazole antifungal agent. Proceedings (Baylor University Medical Center). 2007;20(2):188-196. PMID: PMC1849883 </ref><br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742630Sandbox 1234562017-04-19T21:55:52Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, headaches, fever, vomiting, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
It should be taken with food to help absorption and is generally taken 3 times a day in 200 mg doses. For fungi that have been unmanageable through other treatments, 800 mg are given daily 2 or 4 times a day to treat infection <ref name="greer"> Greer ND. Posaconazole (Noxafil): a new triazole antifungal agent. Proceedings (Baylor University Medical Center). 2007;20(2):188-196. PMID: PMC1849883 </ref><br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742621Sandbox 1234562017-04-19T21:41:19Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals <ref name="formularyjournal" />.<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742618Sandbox 1234562017-04-19T21:39:47Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals <ref name="formularyjournal" />.<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742617Sandbox 1234562017-04-19T21:38:52Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against ''Candida'' species, and a fungicidal against ''Aspergillus'' species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. ''Aspergillus'' is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive ''Candida'' and ''Aspergillus'' infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742614Sandbox 1234562017-04-19T21:32:30Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. It was seen that in a group of patients undergoing chemotherapy or stem cell transplantation, posaconazole was the most effective at the prevention and elimination of invasive fungal infections when compared to alternative treatment options <ref> DOI: 10.1056/NEJMoa061094 </ref>. <br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug <ref name="dekkers"/>. <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742611Sandbox 1234562017-04-19T21:24:25Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug (link to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896980/ ). <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by ''Candida'' or ''Aspergillus'' species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. ''Candida'' (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742609Sandbox 1234562017-04-19T21:22:11Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug (link to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896980/ ). <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name= "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742607Sandbox 1234562017-04-19T21:21:16Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug (link to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896980/ ). <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref name="dekkers">doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances <ref name" "dekkers"/>. <br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742606Sandbox 1234562017-04-19T21:19:09Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> through an ionic bond between a neutral nitrogen atom on <scene name='75/756730/Posaconazole/1'>posaconazole</scene> and an iron atom on heme located in the active site of <scene name='75/756730/Cyp51/1'>CYP51</scene> . This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug (link to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896980/ ). <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155160/)<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742605Sandbox 1234562017-04-19T21:15:29Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (PDB ID: 5FSA). <br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug (link to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896980/ ). <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155160/)<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742604Sandbox 1234562017-04-19T21:14:30Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme 14-alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug (link to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896980/ ). <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155160/)<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742603Sandbox 1234562017-04-19T21:13:23Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species and derived from a similar triazole antifungal agent, Itraconazole. It is especially effective against filamentous fungi. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup2/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The entirety of the scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Pharmaceutical Information ==<br />
Noxafil is available in several forms, such as an oral suspension, gastro resistant tablets, and a concentrate (EMA). The pharmacokinetics and pharmacodynamics of Noxafil, specifically posaconazole, have been studied extensively and continue to be studied today to further improve the overall effectivenes of the drug (link to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896980/ ). <br />
Some of the most commonly reported side effects include nausea, diarrhea, mild headaches, tiredness, and dizziness. <br />
Posaconazole has not been found to be have significant dose-limiting toxicity and has more reduced drug-drug interactions than many other antifungals (formularyjournal) <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155160/)<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742598Sandbox 1234562017-04-19T21:09:28Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (<scene name='75/756730/Cyp51/1'>CYP51</scene>) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155160/)<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742595Sandbox 1234562017-04-19T20:59:51Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, <scene name='75/756730/Posaconazole/1'>posaconazole</scene> (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155160/)<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742591Sandbox 1234562017-04-19T20:52:11Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The scene shows the crystal <scene name='75/756730/Structure/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations). There has been a noticeable increase in the incidence of invasive fungal infections particularly within patients receiving chemotherapy and transplant recipients. These patients are extremely susceptible because of their compromised immune system and the pressures from antibiotic usage, which is why invasive fungal infections are on the rise with these medical advances. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155160/)<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742582Sandbox 1234562017-04-19T20:39:41Z<p>Madelyn Smith: </p>
<hr />
<div><StructureSection load='5FSA' size='350' side='right' caption='PDB ID: 5FSA' scene=''><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The scene shows the crystal <scene name='75/756730/5fsa/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742578Sandbox 1234562017-04-19T20:36:48Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='PDB ID: 5FSA' /><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
[[Image:Posaconazole2.png]] <br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The scene shows the crystal <scene name='75/756730/5fsa/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=File:Posaconazole2.png&diff=2742577File:Posaconazole2.png2017-04-19T20:32:53Z<p>Madelyn Smith: </p>
<hr />
<div></div>Madelyn Smithhttps://proteopedia.org/index.php?title=File:Posaconazole.png&diff=2742575File:Posaconazole.png2017-04-19T20:27:44Z<p>Madelyn Smith: </p>
<hr />
<div></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742573Sandbox 1234562017-04-19T20:26:55Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='PDB ID: 5FSA' /><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The scene shows the crystal <scene name='75/756730/5fsa/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those with different pre-existing infections or more seriously for those with immunologically suppressing diseases like HIV/AIDS. "Candida" (thrush/Candidiasis) is the most common yeast pathogen that typically grows in human mucosal surfaces like the intestinal tract and causes pathology when it becomes overgrown. "Aspergillus" is the most common mold pathogen leading to invasive fungal infections, termed Aspergillosis, when it is acquired from the surrounding environment <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742560Sandbox 1234562017-04-19T20:03:54Z<p>Madelyn Smith: added green link</p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='PDB ID: 5FSA' /><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. The scene shows the crystal <scene name='75/756730/5fsa/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those.... "Candida" (thrush) is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742559Sandbox 1234562017-04-19T20:01:18Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole PDB ID: 5FSA' /><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of the CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. <br />
<br />
Crystal <scene name='75/756730/5fsa/1'>structure</scene> of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole<br />
<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor through an ionic bond between a neutral nitrogen atom on posaconazole and an iron atom on heme (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51). This prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those.... "Candida" (thrush) is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742546Sandbox 1234562017-04-19T18:13:37Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole PDB ID: 5FSA' /><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines (green link) and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. <br />
<br />
(explanation of green links/figures?)<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51) which prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those.... "Candida" (thrush) is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742545Sandbox 1234562017-04-19T18:11:33Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole PDB ID: 5FSA' /><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines (green link) and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref name="drugbank">Posaconazole. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB01263<br />
Accession Number: DB01263 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. <br />
<br />
(explanation of green links/figures?)<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51) which prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those.... "Candida" (thrush) is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742544Sandbox 1234562017-04-19T17:55:28Z<p>Madelyn Smith: citations added</p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole PDB ID: 5FSA' /><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s <ref name="acs">Posaconazole. (2011, December 12). Retrieved from https://www.acs.org/content/acs/en/molecule-of-the-week/archive/p/molecule-of-the-week-posaconazole.html?_ga=1.240614083.1136742914.1490798730 </ref>, and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus'' species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines (green link) and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref>PMID: 21059682 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi <ref name="formularyjournal">Sircar-Ramsewak,, F., Nicolau, D. P., & Kuti, J. L. (2005). Focus on posaconazole: A novel triazole antifungal for the treatment of invasive fungal infections. Formulary Journal - Modern Medicine Network </ref>. <br />
<br />
(explanation of green links/figures?)<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51) which prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="formularyjournal" />. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those.... "Candida" (thrush) is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections <ref name="soysal">doi: 10.2147/IDR.S65592</ref>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742542Sandbox 1234562017-04-19T17:37:22Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'' and ''Aspergillus''species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death <ref name=pubchem>National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</ref>. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines (green link) and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref>PMID: 21059682 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) <ref name="groll">doi:10.1586/14787210.3.4.467</ref><ref>doi: 10.1086/523576</ref>. The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi (formularyjournal.com). <br />
<br />
(explanation of green links/figures?)<br />
<br />
==Mechanism==<br />
When administered, posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51) which prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol <ref name="groll"/>. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation?). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species <ref name="soysal">doi: 10.2147/IDR.S65592</ref>.<br />
<br />
== Relevance ==<br />
Invasive fungal infections, commonly caused by "Candida" or "Aspergillus" species affect patients that are immunocompromised such as those.... "Candida" (thrush) is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections <ref name="soysal"/>. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole)<ref>doi: 10.1007/s12281-016-0255-4</ref> . Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients. (Add more & add citations).<br />
<br />
== References ==<br />
<references/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742536Sandbox 1234562017-04-19T16:39:50Z<p>Madelyn Smith: heme cofactor green link</p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'', ''Aspergillus'', and "Fusarium" species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines (green link) and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref>PMID: 21059682 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the <scene name='75/756730/Hemegroup/1'>heme cofactor</scene> in the active site of CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) (Groll)(academic.oup.com). The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi (formularyjournal.com). <br />
<br />
(explanation of green links/figures?)<br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51) which prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species (formularyjournal.com)<br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections (NCBI). Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
== References ==<br />
<references/> (need to fix)<br />
1. Dekkers, B. G. J., Bakker, M., van der Elst, K. C. M., Sturkenboom, M. G. G., Veringa, A., Span, L. F. R., & Alffenaar, J.-W. C. (2016). Therapeutic Drug Monitoring of Posaconazole: an Update. Current Fungal Infection Reports, 10, 51–61. http://doi.org/10.1007/s12281-016-0255-4<br />
2. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
3. Groll, A. H., & Walsh, T. J. (2005). Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Review of Anti-infective Therapy, 3(4), 467-487. doi:10.1586/14787210.3.4.467<br />
4. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]<br />
5. National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2742534Sandbox 1234562017-04-19T16:20:10Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
<scene name='75/756730/Hemegroup/1'>TextToBeDisplayed</scene><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'', ''Aspergillus'', and "Fusarium" species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines (green link) and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref>PMID: 21059682 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the heme cofactor in the active site of CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) (Groll)(academic.oup.com). The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi (formularyjournal.com). <br />
<br />
(explanation of green links/figures?)<br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51) which prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species (formularyjournal.com)<br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections (NCBI). Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
== References ==<br />
<references/> (need to fix)<br />
1. Dekkers, B. G. J., Bakker, M., van der Elst, K. C. M., Sturkenboom, M. G. G., Veringa, A., Span, L. F. R., & Alffenaar, J.-W. C. (2016). Therapeutic Drug Monitoring of Posaconazole: an Update. Current Fungal Infection Reports, 10, 51–61. http://doi.org/10.1007/s12281-016-0255-4<br />
2. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
3. Groll, A. H., & Walsh, T. J. (2005). Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Review of Anti-infective Therapy, 3(4), 467-487. doi:10.1586/14787210.3.4.467<br />
4. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]<br />
5. National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2740666Sandbox 1234562017-04-19T05:20:24Z<p>Madelyn Smith: minor text edit & added rough citations & green link indications</p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
==Introduction== <br />
Noxafil, also known as posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'', ''Aspergillus'', and "Fusarium" species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole (green link) is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines (green link) and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref>PMID: 21059682 </ref>. The extended side chain residues and hydrophobic contacts enhances antifungal activity by allowing tighter binding affinities to the heme cofactor in the active site of CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) (Groll)(academic.oup.com). The tighter binding affinity of posaconazole makes it less susceptible to be affected by mutations in the enzyme resulting in resistance of fungi (formularyjournal.com). <br />
<br />
(explanation of green links/figures?)<br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor (make green link) located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51) which prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation). In this way, posaconazole acts as a fungistatic against "Candida" species, and a fungicidal against "Asperigillus" species (formularyjournal.com)<br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections (NCBI). Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
== References ==<br />
<references/> (need to fix)<br />
1. Dekkers, B. G. J., Bakker, M., van der Elst, K. C. M., Sturkenboom, M. G. G., Veringa, A., Span, L. F. R., & Alffenaar, J.-W. C. (2016). Therapeutic Drug Monitoring of Posaconazole: an Update. Current Fungal Infection Reports, 10, 51–61. http://doi.org/10.1007/s12281-016-0255-4<br />
2. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
3. Groll, A. H., & Walsh, T. J. (2005). Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Review of Anti-infective Therapy, 3(4), 467-487. doi:10.1586/14787210.3.4.467<br />
4. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]<br />
5. National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2740653Sandbox 1234562017-04-19T03:56:48Z<p>Madelyn Smith: revised text (took away function section0</p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is a broad spectrum antifungal drug mainly used to treat fungal infections caused by ''Candida'', ''Aspergillus'', and "Fusarium" species. Noxafil is also often used when other antifungal medicines are not able to be tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works through inhibiting the biosynthesis of ergosterol in the fungal cell membrane, an essential factor that if inhibited, will lead to prevention of cell growth and ultimately death. <br />
<br />
==Function/Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
The primary component of Noxafil, posaconazole is a potent, broad-spectrum antifungal drug. It was derived from a similar triazole antifungal agent, Itraconazole. The differences in structure are that the chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with fluorines and that the triazolone sidechain is hydroxylated in the posaconazole structure<ref>PMID: 21059682 </ref>. The extended side chain residues of posaconazole enhances its antifungal activity by allowing tighter binding affinities to the heme cofactor in the active site of CYP450-dependent enzyme lanosterol alpha-demthylase (CYP51) (Groll). The tighter binding affinity of posaconazole makes it less susceptible to be affected by antifungal resistant mutations in the enzyme (formularyjournal.com) <br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as a potent and broad-spectrum antifungal drug by binding to the heme cofactor located in the active site of CYP450-dependent enzyme lanosterol alpha-demethylase (CYP51) which prevents biosynthesis of ergosterol and causes accumulation of toxic methylated sterol precursor, 14-alpha-methylsterol. Ergosterol is an essential performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions (citation) . In this way, Posaconazole acts both as <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
== References ==<br />
<references/> (need to fix)<br />
1. Dekkers, B. G. J., Bakker, M., van der Elst, K. C. M., Sturkenboom, M. G. G., Veringa, A., Span, L. F. R., & Alffenaar, J.-W. C. (2016). Therapeutic Drug Monitoring of Posaconazole: an Update. Current Fungal Infection Reports, 10, 51–61. http://doi.org/10.1007/s12281-016-0255-4<br />
2. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
3. Groll, A. H., & Walsh, T. J. (2005). Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Review of Anti-infective Therapy, 3(4), 467-487. doi:10.1586/14787210.3.4.467<br />
4. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]<br />
5. National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2740383Sandbox 1234562017-04-18T01:56:13Z<p>Madelyn Smith: added rough green link and references - still need in text citations</p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to act as a potent, broad-spectrum antifungal drug that was derived from another triazole antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 </ref>. Altered side chain residues of posaconazole enhances its antifungal activity...(put specific sidechains here? Or in mechanisms?)<br />
<br />
== Function ==<br />
The primary component of Noxafil, posaconazole, is a broad-spectrum antifungal agent that has activity against Candida species, Aspergillus species, Cryptococcus neoformans, the zygomycetes, and other filamentous fungi. It is commonly used in immunocompromised patients or patients at high risk for fungal infections. Posaconazole <br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol <scene name='75/756730/Protein_ligand/1'>14-α- demethylase </scene>x, a P-450 dependant fungal enzyme containing heme as a cofactor (Groll)(). Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
==Pharmacology==<br />
<br />
<br />
== References ==<br />
<references/> (need to fix)<br />
1. Dekkers, B. G. J., Bakker, M., van der Elst, K. C. M., Sturkenboom, M. G. G., Veringa, A., Span, L. F. R., & Alffenaar, J.-W. C. (2016). Therapeutic Drug Monitoring of Posaconazole: an Update. Current Fungal Infection Reports, 10, 51–61. http://doi.org/10.1007/s12281-016-0255-4<br />
2. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
3. Groll, A. H., & Walsh, T. J. (2005). Posaconazole: clinical pharmacology and potential for management of fungal infections. Expert Review of Anti-infective Therapy, 3(4), 467-487. doi:10.1586/14787210.3.4.467<br />
4. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]<br />
5. National Center for Biotechnology Information. PubChem Compound Database; CID=468595, https://pubchem.ncbi.nlm.nih.gov/compound/468595</div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2740381Sandbox 1234562017-04-18T01:26:24Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to act as a potent, broad-spectrum antifungal drug that was derived from another triazole antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 </ref>. Altered side chain residues of posaconazole enhances its antifungal activity...(put specific sidechains here? Or in mechanisms?)<br />
<br />
== Function ==<br />
The primary component of Noxafil, posaconazole, is a broad-spectrum antifungal agent that has activity against Candida species, Aspergillus species, Cryptococcus neoformans, the zygomycetes, and other filamentous fungi. It is commonly used in immunocompromised patients or patients at high risk for fungal infections. Posaconazole <br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol <scene name='75/756730/Protein_ligand/1'>14-α- demethylase </scene>x, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
==Pharmacology==<br />
<br />
<br />
== References ==<br />
<references/> (need to fix)<br />
1. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
2. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]</div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2734101Sandbox 1234562017-03-29T23:18:00Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil falls under the triazole class of antifungal drugs and thus works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to act as a potent, broad-spectrum antifungal drug that was derived from another triazole antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 </ref>. Altered side chain residues of posaconazole enhances its antifungal activity...(put specific sidechains here? Or in mechanisms?)<br />
<br />
== Function ==<br />
The primary component of Noxafil, posaconazole, is a broad-spectrum antifungal agent that has activity against Candida species, Aspergillus species, Cryptococcus neoformans, the zygomycetes, and other filamentous fungi. It is commonly used in immunocompromised patients or patients at high risk for fungal infections. Posaconazole <br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
==Pharmacology==<br />
<br />
<br />
== References ==<br />
<references/> (need to fix)<br />
1. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
2. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]</div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2734083Sandbox 1234562017-03-29T22:32:51Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, was developed by Schering-Plough in the mid-2000s (acs.org), and is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to potently act as a triazole broad-spectrum antifungal drug that was derived from the antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 </ref>.<br />
<br />
== Function ==<br />
The primary component of Noxafil, posaconazole, is a broad-spectrum antifungal agent that has activity against Candida species, Aspergillus species, Cryptococcus neoformans, the zygomycetes, and other filamentous fungi. It is commonly used in immunocompromised patients or patients at high risk for fungal infections. <br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
==Pharmacology==<br />
<br />
== References ==<br />
<references/> (need to fix)<br />
1. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
2. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]</div>Madelyn Smithhttps://proteopedia.org/index.php?title=Sandbox_123456&diff=2733841Sandbox 1234562017-03-29T15:17:53Z<p>Madelyn Smith: New page: <Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the ...</p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to potently act as a triazole broad-spectrum antifungal drug that was derived from the antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 </ref>.<br />
<br />
== Function ==<br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
==Pharmacology==<br />
<br />
== References ==<br />
<references/><br />
1. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
2. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]</div>Madelyn Smithhttps://proteopedia.org/index.php?title=User:Madelyn_Smith/Sandbox_1&diff=2733840User:Madelyn Smith/Sandbox 12017-03-29T15:09:20Z<p>Madelyn Smith: </p>
<hr />
<div><Structure load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to potently act as a triazole broad-spectrum antifungal drug that was derived from the antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 </ref>.<br />
<br />
== Function ==<br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
==Pharmacology==<br />
<br />
== References ==<br />
<references/><br />
1. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
2. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]</div>Madelyn Smithhttps://proteopedia.org/index.php?title=User:Madelyn_Smith/Sandbox_1&diff=2733838User:Madelyn Smith/Sandbox 12017-03-29T15:00:24Z<p>Madelyn Smith: </p>
<hr />
<div><Structure <applet load='4j14' size='350' frame='true' align='right' caption='Crystal Structure of Human Cytochrome P450 CYP46A1 with Posaconazole Bound'/><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to potently act as a triazole broad-spectrum antifungal drug that was derived from the antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 </ref>.<br />
<br />
== Function ==<br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
==Pharmacology==<br />
<br />
== References ==<br />
<references/><br />
1. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
2. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]</div>Madelyn Smithhttps://proteopedia.org/index.php?title=User:Madelyn_Smith/Sandbox_1&diff=2732930User:Madelyn Smith/Sandbox 12017-03-29T13:19:32Z<p>Madelyn Smith: </p>
<hr />
<div><Structure <applet load='4j14' size='350' frame='true' align='right' caption='Crystal Structure of Human Cytochrome P450 CYP46A1 with Posaconazole Bound'/><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to potently act as a triazole broad-spectrum antifungal drug that was derived from the antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 <ref/>.<br />
<br />
== Function ==<br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
== Relevance ==<br />
Invasive fungal infections, like Candida, Aspergillus, coccidiomycosis, affect patients that are immunocompromised more intensely and are relatively more common in immunocompromised patients. Candida is the most common yeast pathogen while Aspergillus is the most common mold pathogen leading to invasive fungal infections. Noxafil oral suspension is the best form of treatment for invasive Candida and Aspergillus infections in patients 13 years and older who are severely immunocompromised. Noxafil is also more effective at preventing invasive fungal infections in immunocompromised patients when compared to other antifungal treatments (fluconazole and itraconazole). Overall, Noxafil displays fewer cases of invasive fungal infections and is also a more affordable treatment for immunocompromised patients.<br />
<br />
==Pharmacology==<br />
<br />
== References ==<br />
<references/><br />
1. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
2. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]</div>Madelyn Smithhttps://proteopedia.org/index.php?title=User:Madelyn_Smith/Sandbox_1&diff=2732699User:Madelyn Smith/Sandbox 12017-03-28T21:12:47Z<p>Madelyn Smith: </p>
<hr />
<div>[[Link title]]<br />
<Structure <applet load='4j14' size='350' frame='true' align='right' caption='Crystal Structure of Human Cytochrome P450 CYP46A1 with Posaconazole Bound'/><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C<sub>37</sub>H<sub>42</sub>F<sub>2</sub>N<sub>8</sub>O<sub>4</sub><br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
The structure of Posaconazole allows it to potently act as a triazole broad-spectrum antifungal drug that was derived from the antifungal agent, Itraconazole. The differences in structure are that the Chlorine substituents in the aromatic ring on the left-hand side of the images are replaces with Fluorines and that the triazolone sidechain is hydroxylated in the Posaconazole structure<ref>PMID: 21059682 <ref/>.<br />
<br />
== Function ==<br />
<br />
== Relevance ==<br />
<br />
==Mechanism==<br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
==Pharmacology==<br />
<br />
== References ==<br />
<references/><br />
1. Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID: 21059682<br />
2. Nagappan V, Deresinski S: Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15;45(12):1610-7. doi: 10.1086/523576. [PubMed:18190324 ]</div>Madelyn Smithhttps://proteopedia.org/index.php?title=User:Madelyn_Smith/Sandbox_1&diff=2732695User:Madelyn Smith/Sandbox 12017-03-28T20:49:06Z<p>Madelyn Smith: </p>
<hr />
<div>[[Link title]]<br />
<Structure <applet load='4j14' size='350' frame='true' align='right' caption='Crystal Structure of Human Cytochrome P450 CYP46A1 with Posaconazole Bound'/><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C37H42F2N8O4<br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
== Function ==<br />
<br />
== Relevance ==<br />
<br />
==Mechanism==<br />
<Structure <applet load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
==Pharmacology==<br />
<br />
== References ==<br />
<references/><br />
PCID: 468595 <br />
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000610/human_med_000937.jsp&mid=WC0b01ac058001d124 <br />
http://www.tandfonline.com/doi/full/10.1586/14787210.3.4.467</div>Madelyn Smithhttps://proteopedia.org/index.php?title=User:Madelyn_Smith/Sandbox_1&diff=2732692User:Madelyn Smith/Sandbox 12017-03-28T20:45:40Z<p>Madelyn Smith: </p>
<hr />
<div>[[Link title]]<br />
<Structure <applet load='4j14' size='350' frame='true' align='right' caption='Crystal Structure of Human Cytochrome P450 CYP46A1 with Posaconazole Bound'/><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C37H42F2N8O4<br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
== Function ==<br />
<br />
== Relevance ==<br />
<br />
==Mechanism==<br />
<Structure <applet load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
==Pharmacology==<br />
<br />
== References ==<br />
<references /> <br />
<ref> PCID: 468595 <ref/><br />
<ref> http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000610/human_med_000937.jsp&mid=WC0b01ac058001d124 <ref/><br />
<ref> http://www.tandfonline.com/doi/full/10.1586/14787210.3.4.467 <ref/></div>Madelyn Smithhttps://proteopedia.org/index.php?title=File:4j14_(1).pdb&diff=2732532File:4j14 (1).pdb2017-03-28T01:16:02Z<p>Madelyn Smith: Crystal Structure of Human Cytochrome P450 CYP46A1 with Posaconazole Bound</p>
<hr />
<div>Crystal Structure of Human Cytochrome P450 CYP46A1 with Posaconazole Bound</div>Madelyn Smithhttps://proteopedia.org/index.php?title=User:Madelyn_Smith/Sandbox_1&diff=2732500User:Madelyn Smith/Sandbox 12017-03-27T19:47:44Z<p>Madelyn Smith: </p>
<hr />
<div>[[Link title]]<br />
<Structure <applet load='4j14' size='350' frame='true' align='right' caption='Crystal Structure of Human Cytochrome P450 CYP46A1 with Posaconazole Bound'/><br />
<br />
==Introduction== <br />
Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death. <br />
<br />
==Structure==<br />
*Chemical Formula: C37H42F2N8O4<br />
*Molecular Weight: 700.792 g/mol <br />
*IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one<br />
<br />
== Function ==<br />
<br />
== Relevance ==<br />
<br />
==Mechanism==<br />
<Structure <applet load='5FSA' size='350' frame='true' align='right' caption='Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole' /><br />
When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic. <br />
<br />
==Pharmacology==<br />
<br />
== References ==</div>Madelyn Smith