4zzx - Revision history

OCA at 11:01, 10 January 2024

OCA — Wed, 10 Jan 2024 11:01:48 GMT

←Older revision		Revision as of 11:01, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4zzx]] is a 2 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=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4zzx]] is a 2 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=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSU:2-(3-METHOXYPROPYL)-3-OXO-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>FSU</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]] 1.65Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSU:2-(3-METHOXYPROPYL)-3-OXO-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>FSU</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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [https://pdbe.org/4zzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [https://www.ebi.ac.uk/pdbsum/4zzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zzx 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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [https://pdbe.org/4zzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [https://www.ebi.ac.uk/pdbsum/4zzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zzx ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:48, 18 May 2023

OCA — Thu, 18 May 2023 07:48:37 GMT

←Older revision		Revision as of 07:48, 18 May 2023
Line 1:		Line 1:

	==Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor==		==Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor==
-	<StructureSection load='4zzx' size='340' side='right' caption='[[4zzx]], [[Resolution\|resolution]] 1.65Å' scene=''>	+	<StructureSection load='4zzx' size='340' side='right'caption='[[4zzx]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zzx]] is a 2 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=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zzx]] is a 2 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=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSU:2-(3-METHOXYPROPYL)-3-OXO-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>FSU</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSU:2-(3-METHOXYPROPYL)-3-OXO-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>FSU</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zzy\|4zzy]], [[4zzz\|4zzz]], [[5a00\|5a00]]</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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [https://pdbe.org/4zzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [https://www.ebi.ac.uk/pdbsum/4zzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zzx 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/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [~~http~~://pdbe.org/4zzx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4zzx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4zzx ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.	+	[https://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_HUMAN] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
-	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]	+	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Borghi, D]]	+	[[Category: Large Structures]]
-	[[Category: Busel~~, A A~~]]	+	[[Category: Borghi D]]
-	[[Category: Caprera, F]]	+	[[Category: Busel AA]]
-	[[Category: Casale, E]]	+	[[Category: Caprera F]]
-	[[Category: Ciomei, M]]	+	[[Category: Casale E]]
-	[[Category: Cirla, A]]	+	[[Category: Ciomei M]]
-	[[Category: Corti, E]]	+	[[Category: Cirla A]]
-	[[Category: DAnello, M]]	+	[[Category: Corti E]]
-	[[Category: Donati, D]]	+	[[Category: DAnello M]]
-	[[Category: Fasolini, M]]	+	[[Category: Donati D]]
-	[[Category: Felder~~, E R~~]]	+	[[Category: Fasolini M]]
-	[[Category: Forte, B]]	+	[[Category: Felder ER]]
-	[[Category: Galvani, A]]	+	[[Category: Forte B]]
-	[[Category: Isacchi, A]]	+	[[Category: Galvani A]]
-	[[Category: Khvat, A]]	+	[[Category: Isacchi A]]
-	[[Category: Krasavin~~, M Y~~]]	+	[[Category: Khvat A]]
-	[[Category: Lupi, R]]	+	[[Category: Krasavin MY]]
-	[[Category: Montagnoli, A]]	+	[[Category: Lupi R]]
-	[[Category: Orsini, P]]	+	[[Category: Montagnoli A]]
-	[[Category: Papeo, G]]	+	[[Category: Orsini P]]
-	[[Category: Perego, R]]	+	[[Category: Papeo G]]
-	[[Category: Pesenti, E]]	+	[[Category: Perego R]]
-	[[Category: Pezzetta, D]]	+	[[Category: Pesenti E]]
-	[[Category: Posteri, H]]	+	[[Category: Pezzetta D]]
-	[[Category: Rainoldi, S]]	+	[[Category: Posteri H]]
-	[[Category: RiccardiSirtori, F]]	+	[[Category: Rainoldi S]]
-	[[Category: Scolaro, A]]	+	[[Category: RiccardiSirtori F]]
-	[[Category: Sola, F]]	+	[[Category: Scolaro A]]
-	[[Category: Zuccotto, F]]	+	[[Category: Sola F]]
-	~~[[Category: Transferase~~]]	+	[[Category: Zuccotto F]]

OCA at 08:12, 6 March 2019

OCA — Wed, 06 Mar 2019 08:12:36 GMT

←Older revision		Revision as of 08:12, 6 March 2019
Line 1:		Line 1:

	==Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor==		==Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor==
-	<StructureSection load='4zzx' size='340' side='right' caption='[[4zzx]], [[Resolution\|resolution]] 1.65Å' scene=''>	+	<StructureSection load='4zzx' size='340' side='right' caption='[[4zzx]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4zzx]] is a 2 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=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4zzx]] is a 2 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=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4zzx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4zzx" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:24, 16 November 2017

OCA — Thu, 16 Nov 2017 16:24:16 GMT

←Older revision		Revision as of 16:24, 16 November 2017
Line 1:		Line 1:
		+
	==Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor==		==Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor==
	<StructureSection load='4zzx' size='340' side='right' caption='[[4zzx]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='4zzx' size='340' side='right' caption='[[4zzx]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zzx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zzx]] is a 2 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=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSU:2-(3-METHOXYPROPYL)-3-OXO-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>FSU</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSU:2-(3-METHOXYPROPYL)-3-OXO-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>FSU</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zzy\|4zzy]], [[4zzz\|4zzz]], [[5a00\|5a00]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zzy\|4zzy]], [[4zzz\|4zzz]], [[5a00\|5a00]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [http://pdbe.org/4zzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [http://www.ebi.ac.uk/pdbsum/4zzx 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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [http://pdbe.org/4zzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [http://www.ebi.ac.uk/pdbsum/4zzx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zzx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Borghi, D]]		[[Category: Borghi, D]]
	[[Category: Busel, A A]]		[[Category: Busel, A A]]

OCA at 07:40, 30 September 2015

OCA — Wed, 30 Sep 2015 07:40:23 GMT

←Older revision		Revision as of 07:40, 30 September 2015
Line 6:		Line 6:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zzy\|4zzy]], [[4zzz\|4zzz]], [[5a00\|5a00]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zzy\|4zzy]], [[4zzz\|4zzz]], [[5a00\|5a00]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [http://www.ebi.ac.uk/pdbsum/4zzx 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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [http://pdbe.org/4zzx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [http://www.ebi.ac.uk/pdbsum/4zzx PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 18:
	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 4zzx" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:40, 12 August 2015

OCA — Wed, 12 Aug 2015 14:40:11 GMT

←Older revision		Revision as of 14:40, 12 August 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor==
		+	<StructureSection load='4zzx' size='340' side='right' caption='[[4zzx]], [[Resolution\|resolution]] 1.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4zzx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZZX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSU:2-(3-METHOXYPROPYL)-3-OXO-2,3-DIHYDRO-1H-ISOINDOLE-4-CARBOXAMIDE'>FSU</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zzy\|4zzy]], [[4zzz\|4zzz]], [[5a00\|5a00]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=4zzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zzx RCSB], [http://www.ebi.ac.uk/pdbsum/4zzx PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PARP2_HUMAN PARP2_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing. However all current compounds unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization around the unselective isoindolinone-4-carboxamide hits 10a and 10b, allowed us to subsequently discover 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoind ole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with temozolomide, in MDA-MB-436 and CAPAN-1 xenograft models, respectively. High resolution X-ray diffraction co-crystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.

-	~~The entry 4zzx is ON HOLD until Paper Publication~~	+	Discovery of 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoind ole-4-carboxamide (NMS-P118): a Potent, Orally Available and Highly Selective PARP-1 Inhibitor for Cancer Therapy.,Papeo GM, Posteri H, Borghi D, Busel AA, Caprera F, Casale E, Ciomei M, Cirla A, Corti E, D'Anello M, Fasolini M, Forte B, Galvani A, Isacchi A, Khvat A, Krasavin MY, Lupi R, Orsini P, Perego R, Pesenti E, Pezzetta D, Rainoldi S, Riccardi-Sirtori F, Scolaro A, Sola F, Zuccotto F, Felder ER, Donati D, Montagnoli A J Med Chem. 2015 Jul 29. PMID:26222319<ref>PMID:26222319</ref>

-	~~Authors: Casale~~, E.~~, Fasolini, M~~.~~, Papeo, G~~.~~, Posteri, H.,~~ Borghi, D., Busel, A.A., Caprera, F., Ciomei, M., Cirla, A., Corti, E., DAnello, M., Fasolini, M., Felder, E.R., Forte, B., Galvani, A., Isacchi, A., Khvat, A., Krasavin, M.Y., Lupi, R., Orsini, P., Perego, R., Pesenti, E., Pezzetta, D., Rainoldi, S., RiccardiSirtori, F., Scolaro, A., Sola, F., Zuccotto, F., Donati, D., Montagnoli, A.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Borghi, D]]
		+	[[Category: Busel, A A]]
		+	[[Category: Caprera, F]]
	[[Category: Casale, E]]		[[Category: Casale, E]]
	[[Category: Ciomei, M]]		[[Category: Ciomei, M]]
	[[Category: Cirla, A]]		[[Category: Cirla, A]]
-	[[Category: ~~Pesenti~~, E]]	+	[[Category: Corti, E]]
-	[[Category: ~~Zuccotto, F]]~~	+	[[Category: DAnello, M]]
-	~~[[Category: Busel, A.A]]~~	+
-	~~[[Category: Forte, B]]~~	+
-	~~[[Category: Caprera, F]]~~	+
-	~~[[Category: Krasavin~~, M.Y]]	+
	[[Category: Donati, D]]		[[Category: Donati, D]]
-	[[Category: Perego, R]]
	[[Category: Fasolini, M]]		[[Category: Fasolini, M]]
-	[[Category: ~~Borghi~~, D]]	+	[[Category: Felder, E R]]
-	[[Category: ~~Sola~~, F]]	+	[[Category: Forte, B]]
-	[[Category: ~~Felder~~, E.R]]	+	[[Category: Galvani, A]]
-	[[Category: ~~Riccardisirtori~~, F]]	+	[[Category: Isacchi, A]]
		+	[[Category: Khvat, A]]
		+	[[Category: Krasavin, M Y]]
		+	[[Category: Lupi, R]]
		+	[[Category: Montagnoli, A]]
	[[Category: Orsini, P]]		[[Category: Orsini, P]]
-	[[Category: ~~Danello~~, M]]	+	[[Category: Papeo, G]]
		+	[[Category: Perego, R]]
		+	[[Category: Pesenti, E]]
	[[Category: Pezzetta, D]]		[[Category: Pezzetta, D]]
	[[Category: Posteri, H]]		[[Category: Posteri, H]]
-	[[Category: ~~Montagnoli~~, A]]	+	[[Category: Rainoldi, S]]
-	[[Category: ~~Galvani~~, ~~A]]~~	+	[[Category: RiccardiSirtori, F]]
-	~~[[Category: Khvat, A~~]]	+
	[[Category: Scolaro, A]]		[[Category: Scolaro, A]]
-	[[Category: ~~Rainoldi~~, S]]	+	[[Category: Sola, F]]
-	[[Category: ~~Corti~~, E]]	+	[[Category: Zuccotto, F]]
-	[[Category: ~~Papeo, G]]~~	+	[[Category: Transferase]]
-	~~[[Category: Isacchi, A]]~~	+
-	~~[[Category: Lupi, R~~]]	+

OCA at 11:12, 20 May 2015

OCA — Wed, 20 May 2015 11:12:09 GMT

←Older revision		Revision as of 11:12, 20 May 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4zzx is ON HOLD	+	The entry 4zzx is ON HOLD until Paper Publication

	Authors: Casale, E., Fasolini, M., Papeo, G., Posteri, H., Borghi, D., Busel, A.A., Caprera, F., Ciomei, M., Cirla, A., Corti, E., DAnello, M., Fasolini, M., Felder, E.R., Forte, B., Galvani, A., Isacchi, A., Khvat, A., Krasavin, M.Y., Lupi, R., Orsini, P., Perego, R., Pesenti, E., Pezzetta, D., Rainoldi, S., RiccardiSirtori, F., Scolaro, A., Sola, F., Zuccotto, F., Donati, D., Montagnoli, A.		Authors: Casale, E., Fasolini, M., Papeo, G., Posteri, H., Borghi, D., Busel, A.A., Caprera, F., Ciomei, M., Cirla, A., Corti, E., DAnello, M., Fasolini, M., Felder, E.R., Forte, B., Galvani, A., Isacchi, A., Khvat, A., Krasavin, M.Y., Lupi, R., Orsini, P., Perego, R., Pesenti, E., Pezzetta, D., Rainoldi, S., RiccardiSirtori, F., Scolaro, A., Sola, F., Zuccotto, F., Donati, D., Montagnoli, A.

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

OCA — Wed, 22 Apr 2015 11:46:34 GMT

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

←Older revision

Revision as of 11:46, 22 April 2015

OCA: New page: '''Unreleased structure''' The entry 4zzx is ON HOLD Authors: Casale, E., Fasolini, M., Papeo, G., Posteri, H., Borghi, D., Busel, A.A., Caprera, F., Ciomei, M., Cirla, A., Corti, E., D...

OCA — Wed, 22 Apr 2015 11:46:33 GMT

New page: '''Unreleased structure''' The entry 4zzx is ON HOLD Authors: Casale, E., Fasolini, M., Papeo, G., Posteri, H., Borghi, D., Busel, A.A., Caprera, F., Ciomei, M., Cirla, A., Corti, E., D...

New page

'''Unreleased structure'''

The entry 4zzx is ON HOLD

Authors: Casale, E., Fasolini, M., Papeo, G., Posteri, H., Borghi, D., Busel, A.A., Caprera, F., Ciomei, M., Cirla, A., Corti, E., DAnello, M., Fasolini, M., Felder, E.R., Forte, B., Galvani, A., Isacchi, A., Khvat, A., Krasavin, M.Y., Lupi, R., Orsini, P., Perego, R., Pesenti, E., Pezzetta, D., Rainoldi, S., RiccardiSirtori, F., Scolaro, A., Sola, F., Zuccotto, F., Donati, D., Montagnoli, A.

Description: Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor
[[Category: Unreleased Structures]]
[[Category: Casale, E]]
[[Category: Ciomei, M]]
[[Category: Cirla, A]]
[[Category: Pesenti, E]]
[[Category: Zuccotto, F]]
[[Category: Busel, A.A]]
[[Category: Forte, B]]
[[Category: Caprera, F]]
[[Category: Krasavin, M.Y]]
[[Category: Donati, D]]
[[Category: Perego, R]]
[[Category: Fasolini, M]]
[[Category: Borghi, D]]
[[Category: Sola, F]]
[[Category: Felder, E.R]]
[[Category: Riccardisirtori, F]]
[[Category: Orsini, P]]
[[Category: Danello, M]]
[[Category: Pezzetta, D]]
[[Category: Posteri, H]]
[[Category: Montagnoli, A]]
[[Category: Galvani, A]]
[[Category: Khvat, A]]
[[Category: Scolaro, A]]
[[Category: Rainoldi, S]]
[[Category: Corti, E]]
[[Category: Papeo, G]]
[[Category: Isacchi, A]]
[[Category: Lupi, R]]