7oep - Revision history

OCA at 07:51, 1 May 2024

2024-05-01T07:51:01Z

←Older revision		Revision as of 07:51, 1 May 2024
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	<StructureSection load='7oep' size='340' side='right'caption='[[7oep]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='7oep' size='340' side='right'caption='[[7oep]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7oep]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OEP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7oep]] 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=7OEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OEP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NV2:5-[1-(1,3-dimethoxypropan-2-yl)-5-morpholin-4-yl-benzimidazol-2-yl]-1,3-dimethyl-pyridin-2-one'>NV2</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</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]] 1.801Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7oeo\|7oeo]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NV2:5-[1-(1,3-dimethoxypropan-2-yl)-5-morpholin-4-yl-benzimidazol-2-yl]-1,3-dimethyl-pyridin-2-one'>NV2</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([https://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=7oep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oep OCA], [https://pdbe.org/7oep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oep RCSB], [https://www.ebi.ac.uk/pdbsum/7oep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oep 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=7oep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oep OCA], [https://pdbe.org/7oep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oep RCSB], [https://www.ebi.ac.uk/pdbsum/7oep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oep ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN]] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>	+	[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Second-generation bromodomain and extra terminal (BET) inhibitors, which selectively target one of the two bromodomains in the BET proteins, have begun to emerge in the literature. These inhibitors aim to help determine the roles and functions of each domain and assess whether they can demonstrate an improved safety profile in clinical settings compared to pan-BET inhibitors. Herein, we describe the discovery of a novel BET BD2-selective chemotype using a structure-based drug design from a hit identified by DNA-encoded library technologies, showing a structural differentiation from key previously reported greater than 100-fold BD2-selective chemotypes GSK620, GSK046, and ABBV-744. Following a structure-based hypothesis for the selectivity and optimization of the physicochemical properties of the series, we identified 60 (GSK040), an in vitro ready and in vivo capable BET BD2-inhibitor of unprecedented selectivity (5000-fold) against BET BD1, excellent selectivity against other bromodomains, and good physicochemical properties. This novel chemical probe can be added to the toolbox used in the advancement of epigenetics research.	+

-	Discovery of a Highly Selective BET BD2 Inhibitor from a DNA-Encoded Library Technology Screening Hit.,Rianjongdee F, Atkinson SJ, Chung CW, Grandi P, Gray JRJ, Kaushansky LJ, Medeiros P, Messenger C, Phillipou A, Preston A, Prinjha RK, Rioja I, Satz AL, Taylor S, Wall ID, Watson RJ, Yao G, Demont EH J Med Chem. 2021 Jul 12. doi: 10.1021/acs.jmedchem.1c00412. PMID:34251219<ref>PMID:34251219</ref>	+	==See Also==
-		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe~~-~~citations 7oep" style="background~~-~~color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chung, C]]	+	[[Category: Chung C]]
-	~~[[Category: Antagonist]]~~	+
-	~~[[Category: Brd2]]~~	+
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Bromodomain containing protein 2]]~~	+
-	~~[[Category: Epigenetic reader]]~~	+
-	~~[[Category: Histone]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Nuclear protein~~]]	+

OCA at 06:38, 25 August 2021

2021-08-25T06:38:01Z

←Older revision		Revision as of 06:38, 25 August 2021
Line 1:		Line 1:

	==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 5-(1-(1,3-dimethoxypropan-2-yl)-5-morpholino-1H-benzo[d]imidazol-2-yl)-1,3-dimethylpyridin-2(1H)-one==		==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 5-(1-(1,3-dimethoxypropan-2-yl)-5-morpholino-1H-benzo[d]imidazol-2-yl)-1,3-dimethylpyridin-2(1H)-one==
-	<StructureSection load='7oep' size='340' side='right'caption='[[7oep]]' scene=''>	+	<StructureSection load='7oep' size='340' side='right'caption='[[7oep]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OEP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7oep]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OEP FirstGlance]. <br>
-	</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=7oep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oep OCA], [https://pdbe.org/7oep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oep RCSB], [https://www.ebi.ac.uk/pdbsum/7oep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oep ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NV2:5-[1-(1,3-dimethoxypropan-2-yl)-5-morpholin-4-yl-benzimidazol-2-yl]-1,3-dimethyl-pyridin-2-one'>NV2</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7oeo\|7oeo]]</div></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([https://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=7oep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oep OCA], [https://pdbe.org/7oep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oep RCSB], [https://www.ebi.ac.uk/pdbsum/7oep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oep ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN]] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Second-generation bromodomain and extra terminal (BET) inhibitors, which selectively target one of the two bromodomains in the BET proteins, have begun to emerge in the literature. These inhibitors aim to help determine the roles and functions of each domain and assess whether they can demonstrate an improved safety profile in clinical settings compared to pan-BET inhibitors. Herein, we describe the discovery of a novel BET BD2-selective chemotype using a structure-based drug design from a hit identified by DNA-encoded library technologies, showing a structural differentiation from key previously reported greater than 100-fold BD2-selective chemotypes GSK620, GSK046, and ABBV-744. Following a structure-based hypothesis for the selectivity and optimization of the physicochemical properties of the series, we identified 60 (GSK040), an in vitro ready and in vivo capable BET BD2-inhibitor of unprecedented selectivity (5000-fold) against BET BD1, excellent selectivity against other bromodomains, and good physicochemical properties. This novel chemical probe can be added to the toolbox used in the advancement of epigenetics research.
		+
		+	Discovery of a Highly Selective BET BD2 Inhibitor from a DNA-Encoded Library Technology Screening Hit.,Rianjongdee F, Atkinson SJ, Chung CW, Grandi P, Gray JRJ, Kaushansky LJ, Medeiros P, Messenger C, Phillipou A, Preston A, Prinjha RK, Rioja I, Satz AL, Taylor S, Wall ID, Watson RJ, Yao G, Demont EH J Med Chem. 2021 Jul 12. doi: 10.1021/acs.jmedchem.1c00412. PMID:34251219<ref>PMID:34251219</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7oep" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chung C]]	+	[[Category: Chung, C]]
		+	[[Category: Antagonist]]
		+	[[Category: Brd2]]
		+	[[Category: Bromodomain]]
		+	[[Category: Bromodomain containing protein 2]]
		+	[[Category: Epigenetic reader]]
		+	[[Category: Histone]]
		+	[[Category: Inhibitor]]
		+	[[Category: Nuclear protein]]

OCA at 08:59, 21 July 2021

2021-07-21T08:59:41Z

←Older revision		Revision as of 08:59, 21 July 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7oep is ON HOLD until Paper Publication~~	+	==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 5-(1-(1,3-dimethoxypropan-2-yl)-5-morpholino-1H-benzo[d]imidazol-2-yl)-1,3-dimethylpyridin-2(1H)-one==
-		+	<StructureSection load='7oep' size='340' side='right'caption='[[7oep]]' scene=''>
-	~~Authors: Chung, C.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OEP FirstGlance]. <br>
-	~~Description:~~ C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 5-(1-(1,3-dimethoxypropan-2-yl)-5-morpholino-1H-benzo[d]imidazol-2-yl)-1,3-dimethylpyridin-2(1H)-one	+	</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=7oep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oep OCA], [https://pdbe.org/7oep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oep RCSB], [https://www.ebi.ac.uk/pdbsum/7oep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oep ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Chung, C]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Chung C]]

OCA: Protected "7oep" [edit=sysop:move=sysop]

2021-05-12T08:23:52Z

Protected "7oep" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:23, 12 May 2021

OCA: New page: '''Unreleased structure''' The entry 7oep is ON HOLD until Paper Publication Authors: Chung, C. Description: C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 5-(1-(1,3-dimethoxypropan-2-yl)-5...

2021-05-12T08:23:51Z

New page: '''Unreleased structure''' The entry 7oep is ON HOLD until Paper Publication Authors: Chung, C. Description: C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 5-(1-(1,3-dimethoxypropan-2-yl)-5...

New page

'''Unreleased structure'''

The entry 7oep is ON HOLD until Paper Publication

Authors: Chung, C.

Description: C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 5-(1-(1,3-dimethoxypropan-2-yl)-5-morpholino-1H-benzo[d]imidazol-2-yl)-1,3-dimethylpyridin-2(1H)-one
[[Category: Unreleased Structures]]
[[Category: Chung, C]]