5dxt - Revision history

OCA at 12:26, 6 March 2024

2024-03-06T12:26:31Z

← Older revision		Revision as of 12:26, 6 March 2024
Line 12:		Line 12:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PK3CA_HUMAN PK3CA_HUMAN] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS.<ref>PMID:21708979</ref>		[https://www.uniprot.org/uniprot/PK3CA_HUMAN PK3CA_HUMAN] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS.<ref>PMID:21708979</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Inhibitors of the class I phosphoinositide 3-kinase (PI3K) isoform PI3Kalpha have received substantial attention for their potential use in cancer therapy. Despite the particular attraction of targeting PI3Kalpha, achieving selectivity for the inhibition of this isoform has proved challenging. Herein we report the discovery of inhibitors of PI3Kalpha that have selectivity over the other class I isoforms and all other kinases tested. In GDC-0032 (3, taselisib), we previously minimized inhibition of PI3Kbeta relative to the other class I insoforms. Subsequently, we extended our efforts to identify PI3Kalpha-specific inhibitors using PI3Kalpha crystal structures to inform the design of benzoxazepin inhibitors with selectivity for PI3Kalpha through interactions with a nonconserved residue. Several molecules selective for PI3Kalpha relative to the other class I isoforms, as well as other kinases, were identified. Optimization of properties related to drug metabolism then culminated in the identification of the clinical candidate GDC-0326 (4).

	The Rational Design of Selective Benzoxazepin Inhibitors of the alpha-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of (S)-2-((2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1 ,4]oxazepin-9-yl)oxy)propanamide (GDC-0326).,Heffron TP, Heald RA, Ndubaku C, Wei B, Augistin M, Do S, Edgar K, Eigenbrot C, Friedman L, Gancia E, Jackson PS, Jones G, Kolesnikov A, Lee LB, Lesnick JD, Lewis C, McLean N, Mortl M, Nonomiya J, Pang J, Price S, Prior WW, Salphati L, Sideris S, Staben ST, Steinbacher S, Tsui V, Wallin J, Sampath D, Olivero AG J Med Chem. 2016 Jan 20. PMID:26741947<ref>PMID:26741947</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 5dxt" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==

OCA at 22:04, 28 June 2023

2023-06-28T22:04:45Z

← Older revision		Revision as of 22:04, 28 June 2023
Line 3:		Line 3:
	<StructureSection load='5dxt' size='340' side='right'caption='[[5dxt]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='5dxt' size='340' side='right'caption='[[5dxt]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5dxt]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DXT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5DXT FirstGlance]. <br>		<table><tr><td colspan='2'>[[5dxt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DXT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5H5:(2S)-2-({2-[1-(PROPAN-2-YL)-1H-1,2,4-TRIAZOL-5-YL]-5,6-DIHYDROIMIDAZO[1,2-D][1,4]BENZOXAZEPIN-9-YL}OXY)PROPANAMIDE'>5H5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>~~</td></tr>~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.25Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dxu\|5dxu]], [[5dxh\|5dxh]]</td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5H5:(2S)-2-({2-[1-(PROPAN-2-YL)-1H-1,2,4-TRIAZOL-5-YL]-5,6-DIHYDROIMIDAZO[1,2-D][1,4]BENZOXAZEPIN-9-YL}OXY)PROPANAMIDE'>5H5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dxt OCA], [https://pdbe.org/5dxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dxt RCSB], [https://www.ebi.ac.uk/pdbsum/5dxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dxt ProSAT]</span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5dxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dxt OCA], [~~http~~://pdbe.org/5dxt PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5dxt RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5dxt PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5dxt ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[~~[http~~://www.uniprot.org/uniprot/PK3CA_HUMAN PK3CA_HUMAN]] Note=Most of the cancer-derived mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS1/KRAS. Interaction with HRAS1/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis. Defects in PIK3CA are associated with colorectal cancer (CRC) [MIM:[~~http~~://omim.org/entry/114500 114500]]. Defects in PIK3CA are a cause of susceptibility to breast cancer (BC) [MIM:[~~http~~://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Defects in PIK3CA are a cause of susceptibility to ovarian cancer (OC) [MIM:[~~http~~://omim.org/entry/167000 167000]]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in PIK3CA may underlie hepatocellular carcinoma (HCC) [MIM:[~~http~~://omim.org/entry/114550 114550]].<ref>PMID:15608678</ref> Defects in PIK3CA are a cause of keratosis seborrheic (KERSEB) [MIM:[~~http~~://omim.org/entry/182000 182000]]. A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance.<ref>PMID:17673550</ref> Defects in PIK3CA are the cause of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:[~~http~~://omim.org/entry/612918 612918]]. CLOVE is a sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth.<ref>PMID:22658544</ref>		[https://www.uniprot.org/uniprot/PK3CA_HUMAN PK3CA_HUMAN] Note=Most of the cancer-derived mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS1/KRAS. Interaction with HRAS1/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis. Defects in PIK3CA are associated with colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]. Defects in PIK3CA are a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Defects in PIK3CA are a cause of susceptibility to ovarian cancer (OC) [MIM:[https://omim.org/entry/167000 167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in PIK3CA may underlie hepatocellular carcinoma (HCC) [MIM:[https://omim.org/entry/114550 114550].<ref>PMID:15608678</ref> Defects in PIK3CA are a cause of keratosis seborrheic (KERSEB) [MIM:[https://omim.org/entry/182000 182000]. A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance.<ref>PMID:17673550</ref> Defects in PIK3CA are the cause of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:[https://omim.org/entry/612918 612918]. CLOVE is a sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth.<ref>PMID:22658544</ref>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/PK3CA_HUMAN PK3CA_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS.<ref>PMID:21708979</ref>		[https://www.uniprot.org/uniprot/PK3CA_HUMAN PK3CA_HUMAN] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS.<ref>PMID:21708979</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Augustin, M]]		[[Category: Augustin M]]
	[[Category: Do, S]]		[[Category: Do S]]
	[[Category: Edgar, K]]		[[Category: Edgar K]]
	[[Category: Eigenbrot, C]]		[[Category: Eigenbrot C]]
	[[Category: Friedman, L]]		[[Category: Friedman L]]
	[[Category: Gancia, E]]		[[Category: Gancia E]]
	[[Category: Heald~~, R A~~]]		[[Category: Heald RA]]
	[[Category: Heffron~~, T P~~]]		[[Category: Heffron TP]]
	[[Category: Jackson~~, P S~~]]		[[Category: Jackson PS]]
	[[Category: Jones, G]]		[[Category: Jones G]]
	[[Category: Kolesnikov, A]]		[[Category: Kolesnikov A]]
	[[Category: Lee~~, L B~~]]		[[Category: Lee LB]]
	[[Category: Lesnick~~, J D~~]]		[[Category: Lesnick JD]]
	[[Category: Lewis, C]]		[[Category: Lewis C]]
	[[Category: McLean, N]]		[[Category: McLean N]]
	[[Category: Mortle, M]]		[[Category: Mortle M]]
	[[Category: Ndubaku, C]]		[[Category: Ndubaku C]]
	[[Category: Nonomiya, J]]		[[Category: Nonomiya J]]
	[[Category: Olivero, A]]		[[Category: Olivero A]]
	[[Category: Pang, J]]		[[Category: Pang J]]
	[[Category: Price, S]]		[[Category: Price S]]
	[[Category: Prior~~, W W~~]]		[[Category: Prior WW]]
	[[Category: Salphati, L]]		[[Category: Salphati L]]
	[[Category: Sampath, D]]		[[Category: Sampath D]]
	[[Category: Sideris, S]]		[[Category: Sideris S]]
	[[Category: Staben~~, S T~~]]		[[Category: Staben ST]]
	[[Category: Steinbacher, S]]		[[Category: Steinbacher S]]
	[[Category: Tsui, V]]		[[Category: Tsui V]]
	[[Category: Wallin, J]]		[[Category: Wallin J]]
	[[Category: Wei~~, B Q]]~~		[[Category: Wei BQ]]
	~~[[Category: Lipid kinase]]~~
	~~[[Category: Transferase-inhibitor complex~~]]

OCA at 08:11, 15 April 2020

2020-04-15T08:11:53Z

← Older revision		Revision as of 08:11, 15 April 2020
Line 1:		Line 1:

	==p110alpha with GDC-0326==		==p110alpha with GDC-0326==
	<StructureSection load='5dxt' size='340' side='right' caption='[[5dxt]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='5dxt' size='340' side='right'caption='[[5dxt]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5dxt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DXT OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca.weizmann.ac~~.~~il/oca-docs~~/fgij/fg.htm?mol=5DXT FirstGlance]. <br>		<table><tr><td colspan='2'>[[5dxt]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DXT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DXT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5H5:(2S)-2-({2-[1-(PROPAN-2-YL)-1H-1,2,4-TRIAZOL-5-YL]-5,6-DIHYDROIMIDAZO[1,2-D][1,4]BENZOXAZEPIN-9-YL}OXY)PROPANAMIDE'>5H5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5H5:(2S)-2-({2-[1-(PROPAN-2-YL)-1H-1,2,4-TRIAZOL-5-YL]-5,6-DIHYDROIMIDAZO[1,2-D][1,4]BENZOXAZEPIN-9-YL}OXY)PROPANAMIDE'>5H5</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dxu\|5dxu]], [[5dxh\|5dxh]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dxu\|5dxu]], [[5dxh\|5dxh]]</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5dxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dxt OCA], [http://pdbe.org/5dxt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dxt RCSB], [http://www.ebi.ac.uk/pdbsum/5dxt PDBsum]</span></td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIK3CA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5dxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dxt OCA], [http://pdbe.org/5dxt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dxt RCSB], [http://www.ebi.ac.uk/pdbsum/5dxt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dxt ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5dxt" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5dxt" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Augustin, M]]		[[Category: Augustin, M]]
	[[Category: Do, S]]		[[Category: Do, S]]

OCA at 10:20, 26 February 2016

2016-02-26T10:20:15Z

← Older revision		Revision as of 10:20, 26 February 2016
Line 1:		Line 1:

	==p110alpha with GDC-0326==		==p110alpha with GDC-0326==
	<StructureSection load='5dxt' size='340' side='right' caption='[[5dxt]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='5dxt' size='340' side='right' caption='[[5dxt]], [[Resolution\|resolution]] 2.25Å' scene=''>

OCA at 02:12, 28 January 2016

2016-01-28T02:12:17Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==p110alpha with GDC-0326==
-The entry 5dxt is ON HOLD  until Paper Publication
+The Rational Design of Selective Benzoxazepin Inhibitors of the alpha-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of (S)-2-((2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1 ,4]oxazepin-9-yl)oxy)propanamide (GDC-0326).,Heffron TP, Heald RA, Ndubaku C, Wei B, Augistin M, Do S, Edgar K, Eigenbrot C, Friedman L, Gancia E, Jackson PS, Jones G, Kolesnikov A, Lee LB, Lesnick JD, Lewis C, McLean N, Mortl M, Nonomiya J, Pang J, Price S, Prior WW, Salphati L, Sideris S, Staben ST, Steinbacher S, Tsui V, Wallin J, Sampath D, Olivero AG J Med Chem. 2016 Jan 20. PMID:26741947<ref>PMID:26741947</ref>
-Authors: Heffron, T.P., Heald, R.A., Ndubaku, C., Wei, B.Q., Augustin, M., Do, S., Edgar, K., Eigenbrot, C., Friedman, L., Gancia, E., Jackson, P.S., Jones, G., Kolesnikov, A., Lee, L.B., Lesnick, J.D., Lewis, C., McLean, N., Mortle, M., Nonomiya, J., Pang, J., Price, S., Prior, W.W., Salphati, L., Sideris, S., Staben, S.T., Steinbacher, S., Tsui, V., Wallin, J., Sampath, D., Olivero, A.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: p110alpha with GDC-0326
+<div class="pdbe-citations 5dxt" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
 [[Category: Do, S]]
-[[Category: Salphati, L]]
+[[Category: Edgar, K]]
-[[Category: Lesnick, J.D]]
+[[Category: Eigenbrot, C]]
-[[Category: Steinbacher, S]]
+[[Category: Friedman, L]]
 [[Category: Jones, G]]
-[[Category: Gancia, E]]
+[[Category: Kolesnikov, A]]
 [[Category: Mortle, M]]
 [[Category: Ndubaku, C]]
 [[Category: Price, S]]
-[[Category: Lee, L.B]]
+[[Category: Prior, W W]]
-[[Category: Pang, J]]
+[[Category: Salphati, L]]
 [[Category: Wallin, J]]
-[[Category: Heald, R.A]]
+[[Category: Wei, B Q]]
-[[Category: Sideris, S]]
+[[Category: Lipid kinase]]
-[[Category: Kolesnikov, A]]
+[[Category: Transferase-inhibitor complex]]

OCA at 11:30, 16 December 2015

2015-12-16T11:30:08Z

← Older revision		Revision as of 11:30, 16 December 2015
Line 7:		Line 7:
	Description: p110alpha with GDC-0326		Description: p110alpha with GDC-0326
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Do, S]]
	[[Category: Salphati, L]]		[[Category: Salphati, L]]
	[[Category: Lesnick, J.D]]		[[Category: Lesnick, J.D]]
Line 15:		Line 16:
	[[Category: Heffron, T.P]]		[[Category: Heffron, T.P]]
	[[Category: Jackson, P.S]]		[[Category: Jackson, P.S]]
			[[Category: Prior, W.W]]
	[[Category: Tsui, V]]		[[Category: Tsui, V]]
			[[Category: Staben, S.T]]
			[[Category: Ndubaku, C]]
			[[Category: Price, S]]
	[[Category: Lee, L.B]]		[[Category: Lee, L.B]]
	[[Category: Pang, J]]		[[Category: Pang, J]]
	[[Category: Wallin, J]]		[[Category: Wallin, J]]
			[[Category: Heald, R.A]]
	[[Category: Sideris, S]]		[[Category: Sideris, S]]
			[[Category: Kolesnikov, A]]
	[[Category: Eigenbrot, C]]		[[Category: Eigenbrot, C]]
	[[Category: Edgar, K]]		[[Category: Edgar, K]]
			[[Category: Olivero, A]]
	[[Category: Friedman, L]]		[[Category: Friedman, L]]
			[[Category: Wei, B.Q]]
	[[Category: Nonomiya, J]]		[[Category: Nonomiya, J]]
			[[Category: Lewis, C]]
	[[Category: Sampath, D]]		[[Category: Sampath, D]]
			[[Category: Mclean, N]]
	[[Category: Augustin, M]]		[[Category: Augustin, M]]
	~~[[Category: Do, S]]~~
	~~[[Category: Prior, W.W]]~~
	~~[[Category: Staben, S.T]]~~
	~~[[Category: Ndubaku, C]]~~
	~~[[Category: Price, S]]~~
	~~[[Category: Heald, R.A]]~~
	~~[[Category: Kolesnikov, A]]~~
	~~[[Category: Olivero, A]]~~
	~~[[Category: Wei, B.Q]]~~
	~~[[Category: Lewis, C]]~~
	~~[[Category: Mclean, N]]~~

OCA at 02:15, 1 December 2015

2015-12-01T02:15:42Z

← Older revision		Revision as of 02:15, 1 December 2015
Line 3:		Line 3:
	The entry 5dxt is ON HOLD until Paper Publication		The entry 5dxt is ON HOLD until Paper Publication

	Authors: Heffron, T.P., Heald, R.A., Ndubaku, C., Wei, BQ., Augustin, M., Do, S., Edgar, K., Eigenbrot, C., Friedman, L., Gancia, E., Jackson, P.S., Jones, G., Kolesnikov, A., Lee, L.B., Lesnick, J.D., Lewis, C., McLean, N., Mortle, M., Nonomiya, J., Pang, J., Price, S., Prior, W.W., Salphati, L., Sideris, S., Staben, S.T., Steinbacher, S., Tsui, V., Wallin, J., Sampath, D., Olivero, A.		Authors: Heffron, T.P., Heald, R.A., Ndubaku, C., Wei, B.Q., Augustin, M., Do, S., Edgar, K., Eigenbrot, C., Friedman, L., Gancia, E., Jackson, P.S., Jones, G., Kolesnikov, A., Lee, L.B., Lesnick, J.D., Lewis, C., McLean, N., Mortle, M., Nonomiya, J., Pang, J., Price, S., Prior, W.W., Salphati, L., Sideris, S., Staben, S.T., Steinbacher, S., Tsui, V., Wallin, J., Sampath, D., Olivero, A.

	Description: p110alpha with GDC-0326		Description: p110alpha with GDC-0326
Line 23:		Line 23:
	[[Category: Edgar, K]]		[[Category: Edgar, K]]
	[[Category: Friedman, L]]		[[Category: Friedman, L]]
	~~[[Category: Wei, Bq]]~~
	[[Category: Nonomiya, J]]		[[Category: Nonomiya, J]]
	[[Category: Sampath, D]]		[[Category: Sampath, D]]
Line 35:		Line 34:
	[[Category: Kolesnikov, A]]		[[Category: Kolesnikov, A]]
	[[Category: Olivero, A]]		[[Category: Olivero, A]]
			[[Category: Wei, B.Q]]
	[[Category: Lewis, C]]		[[Category: Lewis, C]]
	[[Category: Mclean, N]]		[[Category: Mclean, N]]

OCA at 02:47, 16 October 2015

2015-10-16T02:47:04Z

← Older revision		Revision as of 02:47, 16 October 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5dxt is ON HOLD		The entry 5dxt is ON HOLD until Paper Publication

	Authors: Heffron, T.P., Heald, R.A., Ndubaku, C., Wei, BQ., Augustin, M., Do, S., Edgar, K., Eigenbrot, C., Friedman, L., Gancia, E., Jackson, P.S., Jones, G., Kolesnikov, A., Lee, L.B., Lesnick, J.D., Lewis, C., McLean, N., Mortle, M., Nonomiya, J., Pang, J., Price, S., Prior, W.W., Salphati, L., Sideris, S., Staben, S.T., Steinbacher, S., Tsui, V., Wallin, J., Sampath, D., Olivero, A.		Authors: Heffron, T.P., Heald, R.A., Ndubaku, C., Wei, BQ., Augustin, M., Do, S., Edgar, K., Eigenbrot, C., Friedman, L., Gancia, E., Jackson, P.S., Jones, G., Kolesnikov, A., Lee, L.B., Lesnick, J.D., Lewis, C., McLean, N., Mortle, M., Nonomiya, J., Pang, J., Price, S., Prior, W.W., Salphati, L., Sideris, S., Staben, S.T., Steinbacher, S., Tsui, V., Wallin, J., Sampath, D., Olivero, A.

OCA: Protected "5dxt" [edit=sysop:move=sysop]

2015-09-30T13:40:48Z

Protected "5dxt" [edit=sysop:move=sysop]

← Older revision	Revision as of 13:40, 30 September 2015
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5dxt is ON HOLD Authors: Heffron, T.P., Heald, R.A., Ndubaku, C., Wei, BQ., Augustin, M., Do, S., Edgar, K., Eigenbrot, C., Friedman, L., Gancia, E....

2015-09-30T13:40:47Z

New page: '''Unreleased structure''' The entry 5dxt is ON HOLD Authors: Heffron, T.P., Heald, R.A., Ndubaku, C., Wei, BQ., Augustin, M., Do, S., Edgar, K., Eigenbrot, C., Friedman, L., Gancia, E....

New page

'''Unreleased structure'''

The entry 5dxt is ON HOLD

Authors: Heffron, T.P., Heald, R.A., Ndubaku, C., Wei, BQ., Augustin, M., Do, S., Edgar, K., Eigenbrot, C., Friedman, L., Gancia, E., Jackson, P.S., Jones, G., Kolesnikov, A., Lee, L.B., Lesnick, J.D., Lewis, C., McLean, N., Mortle, M., Nonomiya, J., Pang, J., Price, S., Prior, W.W., Salphati, L., Sideris, S., Staben, S.T., Steinbacher, S., Tsui, V., Wallin, J., Sampath, D., Olivero, A.

Description: p110alpha with GDC-0326
[[Category: Unreleased Structures]]
[[Category: Salphati, L]]
[[Category: Lesnick, J.D]]
[[Category: Steinbacher, S]]
[[Category: Jones, G]]
[[Category: Gancia, E]]
[[Category: Mortle, M]]
[[Category: Heffron, T.P]]
[[Category: Jackson, P.S]]
[[Category: Tsui, V]]
[[Category: Lee, L.B]]
[[Category: Pang, J]]
[[Category: Wallin, J]]
[[Category: Sideris, S]]
[[Category: Eigenbrot, C]]
[[Category: Edgar, K]]
[[Category: Friedman, L]]
[[Category: Wei, Bq]]
[[Category: Nonomiya, J]]
[[Category: Sampath, D]]
[[Category: Augustin, M]]
[[Category: Do, S]]
[[Category: Prior, W.W]]
[[Category: Staben, S.T]]
[[Category: Ndubaku, C]]
[[Category: Price, S]]
[[Category: Heald, R.A]]
[[Category: Kolesnikov, A]]
[[Category: Olivero, A]]
[[Category: Lewis, C]]
[[Category: Mclean, N]]