4uwg - Revision history

OCA at 10:37, 10 January 2024

OCA — Wed, 10 Jan 2024 10:37:32 GMT

←Older revision		Revision as of 10:37, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4uwg]] 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=4UWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UWG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4uwg]] 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=4UWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UWG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RBQ:(8S)-2-(MORPHOLIN-4-YL)-9-[2-(PROPAN-2-YLOXY)ETHYL]-8-(TRIFLUOROMETHYL)-6,7,8,9-TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>RBQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RBQ:(8S)-2-(MORPHOLIN-4-YL)-9-[2-(PROPAN-2-YLOXY)ETHYL]-8-(TRIFLUOROMETHYL)-6,7,8,9-TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>RBQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [https://pdbe.org/4uwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [https://www.ebi.ac.uk/pdbsum/4uwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uwg ProSAT]</span></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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [https://pdbe.org/4uwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [https://www.ebi.ac.uk/pdbsum/4uwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uwg ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:46, 29 March 2023

OCA — Wed, 29 Mar 2023 07:46:02 GMT

←Older revision		Revision as of 07:46, 29 March 2023
Line 3:		Line 3:
	<StructureSection load='4uwg' size='340' side='right'caption='[[4uwg]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4uwg' size='340' side='right'caption='[[4uwg]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4uwg]] 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=4UWG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4UWG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4uwg]] 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=4UWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UWG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RBQ:(8S)-2-(MORPHOLIN-4-YL)-9-[2-(PROPAN-2-YLOXY)ETHYL]-8-(TRIFLUOROMETHYL)-6,7,8,9-TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>RBQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RBQ:(8S)-2-(MORPHOLIN-4-YL)-9-[2-(PROPAN-2-YLOXY)ETHYL]-8-(TRIFLUOROMETHYL)-6,7,8,9-TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>RBQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uwf\|4uwf]]</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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [https://pdbe.org/4uwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [https://www.ebi.ac.uk/pdbsum/4uwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uwg ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </span></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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [~~http~~://pdbe.org/4uwg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4uwg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4uwg ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PK3C3_HUMAN PK3C3_HUMAN]] Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis. Required for transport from early to late endosomes.<ref>PMID:7628435</ref> <ref>PMID:14617358</ref> <ref>PMID:20208530</ref>	+	[https://www.uniprot.org/uniprot/PK3C3_HUMAN PK3C3_HUMAN] Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis. Required for transport from early to late endosomes.<ref>PMID:7628435</ref> <ref>PMID:14617358</ref> <ref>PMID:20208530</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
-	*[[Phosphoinositide 3-~~Kinases~~\|Phosphoinositide 3-~~Kinases~~]]	+	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Phosphatidylinositol 3-kinase]]~~	+	[[Category: Abecassis PY]]
-	[[Category: Abecassis~~, P Y~~]]	+	[[Category: Arigon J]]
-	[[Category: Arigon, J]]	+	[[Category: Barriere C]]
-	[[Category: Barriere, C]]	+	[[Category: Benard T]]
-	[[Category: Benard, T]]	+	[[Category: Bertin L]]
-	[[Category: Bertin, L]]	+	[[Category: Bertrand T]]
-	[[Category: Bertrand, T]]	+	[[Category: Bretin F]]
-	[[Category: Bretin, F]]	+	[[Category: Brollo M]]
-	[[Category: Brollo, M]]	+	[[Category: Caron A]]
-	[[Category: Caron, A]]	+	[[Category: Castell C]]
-	[[Category: Castell, C]]	+	[[Category: Clement J]]
-	[[Category: Clement, J]]	+	[[Category: Combet R]]
-	[[Category: Combet, R]]	+	[[Category: Delbarre L]]
-	[[Category: Delbarre, L]]	+	[[Category: Durand F]]
-	[[Category: Durand, F]]	+	[[Category: Dureuil C]]
-	[[Category: Dureuil, C]]	+	[[Category: El-Ahmad Y]]
-	[[Category: El-Ahmad, Y]]	+	[[Category: ElBatti S]]
-	[[Category: ElBatti, S]]	+	[[Category: Fassy F]]
-	[[Category: Fassy, F]]	+	[[Category: Filoche-Romme B]]
-	[[Category: Filoche-Romme, B]]	+	[[Category: Garcia-Echeverria C]]
-	[[Category: Garcia-Echeverria, C]]	+	[[Category: Gay F]]
-	[[Category: Gay, F]]	+	[[Category: Goulaouic H]]
-	[[Category: Goulaouic, H]]	+	[[Category: Labrosse JR]]
-	[[Category: Labrosse~~, J R~~]]	+	[[Category: Lefrancois D]]
-	[[Category: Lefrancois, D]]	+	[[Category: Leroy V]]
-	[[Category: Leroy, V]]	+	[[Category: Letallec JP]]
-	[[Category: Letallec~~, J P~~]]	+	[[Category: Loyau V]]
-	[[Category: Loyau, V]]	+	[[Category: Marquette JP]]
-	[[Category: Marquette~~, J P~~]]	+	[[Category: Mathieu M]]
-	[[Category: Mathieu, M]]	+	[[Category: McCort G]]
-	[[Category: McCort, G]]	+	[[Category: Michot N]]
-	[[Category: Michot, N]]	+	[[Category: Pasquier B]]
-	[[Category: Pasquier, B]]	+	[[Category: Perraut P]]
-	[[Category: Perraut, P]]	+	[[Category: Pilorge F]]
-	[[Category: Pilorge, F]]	+	[[Category: Richepin P]]
-	[[Category: Richepin, P]]	+	[[Category: Ronan B]]
-	[[Category: Ronan, B]]	+	[[Category: Schio L]]
-	[[Category: Schio, L]]	+	[[Category: Sonnefraud V]]
-	[[Category: Sonnefraud, V]]	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:01, 23 May 2019

OCA — Thu, 23 May 2019 08:01:54 GMT

←Older revision		Revision as of 08:01, 23 May 2019
Line 1:		Line 1:

	==Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors==		==Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors==
-	<StructureSection load='4uwg' size='340' side='right' caption='[[4uwg]], [[Resolution\|resolution]] 2.70Å' scene=''>	+	<StructureSection load='4uwg' size='340' side='right'caption='[[4uwg]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4uwg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UWG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UWG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4uwg]] 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=4UWG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UWG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RBQ:(8S)-2-(MORPHOLIN-4-YL)-9-[2-(PROPAN-2-YLOXY)ETHYL]-8-(TRIFLUOROMETHYL)-6,7,8,9-TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>RBQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RBQ:(8S)-2-(MORPHOLIN-4-YL)-9-[2-(PROPAN-2-YLOXY)ETHYL]-8-(TRIFLUOROMETHYL)-6,7,8,9-TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>RBQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uwf\|4uwf]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uwf\|4uwf]]</td></tr>
Line 27:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Phosphatidylinositol 3-kinase]]		[[Category: Phosphatidylinositol 3-kinase]]
	[[Category: Abecassis, P Y]]		[[Category: Abecassis, P Y]]

OCA at 14:16, 11 August 2016

OCA — Thu, 11 Aug 2016 14:16:59 GMT

←Older revision		Revision as of 14:16, 11 August 2016
Line 1:		Line 1:
		+
	==Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors==		==Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors==
	<StructureSection load='4uwg' size='340' side='right' caption='[[4uwg]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4uwg' size='340' side='right' caption='[[4uwg]], [[Resolution\|resolution]] 2.70Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uwf\|4uwf]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uwf\|4uwf]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </span></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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [http://www.ebi.ac.uk/pdbsum/4uwg PDBsum]</span></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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [http://pdbe.org/4uwg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [http://www.ebi.ac.uk/pdbsum/4uwg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uwg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4uwg" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 02:43, 25 December 2014

OCA — Thu, 25 Dec 2014 02:43:13 GMT

←Older revision		Revision as of 02:43, 25 December 2014
Line 8:		Line 8:
	<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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [http://www.ebi.ac.uk/pdbsum/4uwg PDBsum]</span></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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [http://www.ebi.ac.uk/pdbsum/4uwg PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PK3C3_HUMAN PK3C3_HUMAN]] Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis. Required for transport from early to late endosomes.<ref>PMID:7628435</ref> <ref>PMID:14617358</ref> <ref>PMID:20208530</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:56, 26 November 2014

OCA — Wed, 26 Nov 2014 07:56:04 GMT

←Older revision		Revision as of 07:56, 26 November 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors==
		+	<StructureSection load='4uwg' size='340' side='right' caption='[[4uwg]], [[Resolution\|resolution]] 2.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4uwg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UWG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UWG FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RBQ:(8S)-2-(MORPHOLIN-4-YL)-9-[2-(PROPAN-2-YLOXY)ETHYL]-8-(TRIFLUOROMETHYL)-6,7,8,9-TETRAHYDRO-4H-PYRIMIDO[1,2-A]PYRIMIDIN-4-ONE'>RBQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4uwf\|4uwf]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </span></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=4uwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uwg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uwg RCSB], [http://www.ebi.ac.uk/pdbsum/4uwg PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimido-pyrimidinone derivatives. Starting with hit compound 1, medicinal chemistry optimization led to compound 31. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound 31 in human Vps34 illustrated how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound 31 constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology.

-	~~The entry 4uwg is ON HOLD until Paper Publication~~	+	Discovery of (2S)-8-[(3R)-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxo-butyl)-2-(trifluoromethyl) -3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors.,Pasquier B, El-Ahmad Y, Filoche-Romme B, Dureuil-Sizaire C, Fassy F, Abecassis PY, Mathieu M, Bertrand T, Benard T, Barriere C, El Batti S, Letallec JP, Sonnefraud V, Brollo M, Delbarre L, Loyau V, Pilorge F, Bertin L, Richepin P, Arigon J, Labrosse JR, Clement J, Durand F, Combet R, Perraut P, Leroy V, Gay F, Lefrancois D, Bretin F, Marquette JP, Michot N, Caron A, Castell C, Schio L, McCort G, Goulaouic H, Garcia-Echeverria C, Ronan BP J Med Chem. 2014 Nov 17. PMID:25402320<ref>PMID:25402320</ref>

-	~~Authors: Pasquier~~, B.~~, El-Ahmad, Y~~.~~, Filoche~~-~~Romme, B., Dureuil, C., Fassy, F.,~~ Abecassis, P.Y., ~~Mathieu~~, ~~M., Bertrand~~, T., ~~Benard~~, T~~., Barriere, C., ElBatti, S., Letallec, J.P., Sonnefraud, V.~~, Brollo, M., ~~Delbarre~~, ~~L., Loyau, V., Pilorge, F., Bertin, L., Richepin, P., Arigon~~, J., ~~Labrosse, J.~~R~~., Clement, J.~~, Durand, F., ~~Combet~~, R., ~~Perraut~~, P., ~~Leroy, V.~~, Gay, F., Lefrancois, D., ~~Bretin~~, F., Marquette, J.P., Michot, N., ~~Caron~~, A., ~~Castell~~, C., Schio, L~~., McCort, G., Goulaouic, H., Garcia-Echeverria, C.~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo-butyl)-2-(trifluoromethyl)-3~~,~~4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6-one~~: ~~a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Phosphatidylinositol 3-kinase]]
		+	[[Category: Abecassis, P Y]]
		+	[[Category: Arigon, J]]
		+	[[Category: Barriere, C]]
		+	[[Category: Benard, T]]
		+	[[Category: Bertin, L]]
		+	[[Category: Bertrand, T]]
		+	[[Category: Bretin, F]]
		+	[[Category: Brollo, M]]
		+	[[Category: Caron, A]]
		+	[[Category: Castell, C]]
		+	[[Category: Clement, J]]
		+	[[Category: Combet, R]]
		+	[[Category: Delbarre, L]]
		+	[[Category: Durand, F]]
		+	[[Category: Dureuil, C]]
		+	[[Category: El-Ahmad, Y]]
		+	[[Category: ElBatti, S]]
		+	[[Category: Fassy, F]]
		+	[[Category: Filoche-Romme, B]]
		+	[[Category: Garcia-Echeverria, C]]
		+	[[Category: Gay, F]]
		+	[[Category: Goulaouic, H]]
		+	[[Category: Labrosse, J R]]
		+	[[Category: Lefrancois, D]]
		+	[[Category: Leroy, V]]
		+	[[Category: Letallec, J P]]
		+	[[Category: Loyau, V]]
		+	[[Category: Marquette, J P]]
		+	[[Category: Mathieu, M]]
		+	[[Category: McCort, G]]
		+	[[Category: Michot, N]]
		+	[[Category: Pasquier, B]]
		+	[[Category: Perraut, P]]
		+	[[Category: Pilorge, F]]
		+	[[Category: Richepin, P]]
		+	[[Category: Ronan, B]]
		+	[[Category: Schio, L]]
		+	[[Category: Sonnefraud, V]]
		+	[[Category: Transferase]]

OCA: Protected "4uwg" [edit=sysop:move=sysop]

OCA — Wed, 20 Aug 2014 15:14:20 GMT

Protected "4uwg" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:14, 20 August 2014

OCA: New page: '''Unreleased structure''' The entry 4uwg is ON HOLD until Paper Publication Authors: Pasquier, B., El-Ahmad, Y., Filoche-Romme, B., Dureuil, C., Fassy, F., Abecassis, P.Y., Mathieu, M....

OCA — Wed, 20 Aug 2014 15:14:18 GMT

New page: '''Unreleased structure''' The entry 4uwg is ON HOLD until Paper Publication Authors: Pasquier, B., El-Ahmad, Y., Filoche-Romme, B., Dureuil, C., Fassy, F., Abecassis, P.Y., Mathieu, M....

New page

'''Unreleased structure'''

The entry 4uwg is ON HOLD until Paper Publication

Authors: Pasquier, B., El-Ahmad, Y., Filoche-Romme, B., Dureuil, C., Fassy, F., Abecassis, P.Y., Mathieu, M., Bertrand, T., Benard, T., Barriere, C., ElBatti, S., Letallec, J.P., Sonnefraud, V., Brollo, M., Delbarre, L., Loyau, V., Pilorge, F., Bertin, L., Richepin, P., Arigon, J., Labrosse, J.R., Clement, J., Durand, F., Combet, R., Perraut, P., Leroy, V., Gay, F., Lefrancois, D., Bretin, F., Marquette, J.P., Michot, N., Caron, A., Castell, C., Schio, L., McCort, G., Goulaouic, H., Garcia-Echeverria, C.

Description: Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo-butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6-one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors