Sandbox Reserved 1606: Difference between revisions
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===Cancer=== | ===Cancer=== | ||
ABCG2 hinders cancer treatment by contributing to [https://en.wikipedia.org/wiki/Multiple_drug_resistance multidrug resistance] in tumor cells. ABCG2 exports xenbiotics, including vital anti-cancer drugs, which results in the inability to treat cancer cells. Cancer patients typically show high levels of expression of multiple ABC transporters. For example, [https://en.wikipedia.org/wiki/Acute_myeloid_leukemia acute myeloid leukemia] (AML) has shown increased expression of [https://en.wikipedia.org/wiki/P-glycoprotein ABCB1], [https://en.wikipedia.org/wiki/ABCG1 ABCG1], and ABCG2 while childhood AML shows an increased expression in [https://en.wikipedia.org/wiki/ABCA3 ABCA3], ABCB1, [https://en.wikipedia.org/wiki/ABCC3 ABCC3], and ABCG2.<ref name="Marzac"/><ref name="Bartholomae"/> Additionally, pancreatic cancer has shown an upregulation of ABCB4, ABCB11, ABCC1, ABCC3, ABCC5, ABCC10, and ABCG2.<ref name="Mohelnikova-Duchonova"/> | |||
The substrate specificity among ABC transporters varies so this protein family can collectively export a wide variety of substrates and, ultimately, a wide variety of anticancer drugs. ABCG2 has been known to export anticancer drugs such methotrexate, mitoxantrone, topotecan, irinotecan, and flavopiridol (52). Due to the high expression of multiple ABC transporters, treatment of multiple transporters would likely be necessary for successful cancer treatment. | |||
===Inhibitors=== | |||
ABCG2 hinders cancer treatment by contributing to [https://en.wikipedia.org/wiki/Multiple_drug_resistance multidrug resistance] in tumor cells. ABCG2 exports xenbiotics, including vital anti-cancer drugs, which results in the inability to treat cancer cells. The inhibition of ABCG2 would stop the transport of anti-cancer drugs out of cancer cells. Due to the potential for ABCG2 inhibition to aid in cancer treatment, efforts have been made to develop specific inhibitors of ABCG2 and other ABC transporters. Some promising inhibitors were derived from fungal toxin [https://en.wikipedia.org/wiki/Fumitremorgin fumitremorgin C]; however, many of those derivatives developed have neurotoxic effects.<ref name="Jackson"/> | ABCG2 hinders cancer treatment by contributing to [https://en.wikipedia.org/wiki/Multiple_drug_resistance multidrug resistance] in tumor cells. ABCG2 exports xenbiotics, including vital anti-cancer drugs, which results in the inability to treat cancer cells. The inhibition of ABCG2 would stop the transport of anti-cancer drugs out of cancer cells. Due to the potential for ABCG2 inhibition to aid in cancer treatment, efforts have been made to develop specific inhibitors of ABCG2 and other ABC transporters. Some promising inhibitors were derived from fungal toxin [https://en.wikipedia.org/wiki/Fumitremorgin fumitremorgin C]; however, many of those derivatives developed have neurotoxic effects.<ref name="Jackson"/> | ||
ABCG2 <scene name='83/832932/Inhibitor_bound_cavity_1/1'>inhibitors</scene> that bind Cavity 1, acting as competitive inhibitors against ABCG2 substrates. Depending on the size of the inhibitor, one or two molecules can accommodate binding to the cavity and form <scene name='83/832932/Inhibitor_intxns_cavity1/1'>hydrogen bonds, van der Waals, and stacking interactions</scene> within the binding site.<ref name="Jackson"/> Many inhibitors are too big to be transported via the leucine plug resulting in the "clogging" of the transporter. With inhibitors acting as wedges, ABCG2 is locked in the inward-facing conformation and unable to transport molecules out of the cell.<ref name="Manolaridis"/> | ABCG2 <scene name='83/832932/Inhibitor_bound_cavity_1/1'>inhibitors</scene> that bind Cavity 1, acting as competitive inhibitors against ABCG2 substrates. Depending on the size of the inhibitor, one or two molecules can accommodate binding to the cavity and form <scene name='83/832932/Inhibitor_intxns_cavity1/1'>hydrogen bonds, van der Waals, and stacking interactions</scene> within the binding site.<ref name="Jackson"/> Many inhibitors are too big to be transported via the leucine plug resulting in the "clogging" of the transporter. With inhibitors acting as wedges, ABCG2 is locked in the inward-facing conformation and unable to transport molecules out of the cell.<ref name="Manolaridis"/> | ||
</StructureSection> | </StructureSection> | ||
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<ref name="Robey">PMID:29643473</ref> | <ref name="Robey">PMID:29643473</ref> | ||
<ref name="Jackson">PMID:29610494</ref> | <ref name="Jackson">PMID:29610494</ref> | ||
<ref name="Marzac">PMID:21606172</ref> | |||
<ref name="Bartholomae">PMID:26512967</ref> | |||
<ref name="Mohelnikova-Duchonova">PMID:23462326</ref> | |||
<references/> | <references/> | ||
==Student Contributors== | ==Student Contributors== | ||
Julia Pomeroy | Julia Pomeroy | ||
