7nq3 - Revision history

OCA at 06:37, 25 August 2021

OCA — Wed, 25 Aug 2021 06:37:31 GMT

←Older revision		Revision as of 06:37, 25 August 2021
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	==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N4-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-6-((S)-methoxy(phenyl)methyl)-N2-methylpyridine-2,4-dicarboxamide==		==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N4-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-6-((S)-methoxy(phenyl)methyl)-N2-methylpyridine-2,4-dicarboxamide==
-	<StructureSection load='7nq3' size='340' side='right'caption='[[7nq3]]' scene=''>	+	<StructureSection load='7nq3' size='340' side='right'caption='[[7nq3]], [[Resolution\|resolution]] 1.60Å' 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=7NQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NQ3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7nq3]] 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=7NQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NQ3 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=7nq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nq3 OCA], [https://pdbe.org/7nq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nq3 RCSB], [https://www.ebi.ac.uk/pdbsum/7nq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nq3 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=ULQ:6-[(~{S})-methoxy(phenyl)methyl]-~{N}2-methyl-~{N}4-[(1~{S},5~{R})-3-oxabicyclo[3.1.0]hexan-6-yl]pyridine-2,4-dicarboxamide'>ULQ</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;'>[[7npy\|7npy]], [[7npz\|7npz]], [[7nq1\|7nq1]], [[7nq2\|7nq2]], [[7nq0\|7nq0]]</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=7nq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nq3 OCA], [https://pdbe.org/7nq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nq3 RCSB], [https://www.ebi.ac.uk/pdbsum/7nq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nq3 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 ==
		+	Domain-specific BET bromodomain ligands represent an attractive target for drug discovery with the potential to unlock the therapeutic benefits of antagonizing these proteins without eliciting the toxicological aspects seen with pan-BET inhibitors. While we have reported several distinct classes of BD2 selective compounds, namely, GSK620, GSK549, and GSK046, only GSK046 shows high aqueous solubility. Herein, we describe the lead optimization of a further class of highly soluble compounds based upon a picolinamide chemotype. Focusing on achieving >1000-fold selectivity for BD2 over BD1 ,while retaining favorable physical chemical properties, compound 36 was identified as being 2000-fold selective for BD2 over BD1 (Brd4 data) with >1 mg/mL solubility in FaSSIF media. 36 represents a valuable new in vivo ready molecule for the exploration of the BD2 phenotype.
		+
		+	Identification of a Series of N-Methylpyridine-2-carboxamides as Potent and Selective Inhibitors of the Second Bromodomain (BD2) of the Bromo and Extra Terminal Domain (BET) Proteins.,Harrison LA, Atkinson SJ, Bassil A, Chung CW, Grandi P, Gray JRJ, Levernier E, Lewis A, Lugo D, Messenger C, Michon AM, Mitchell DJ, Preston A, Prinjha RK, Rioja I, Seal JT, Taylor S, Wall ID, Watson RJ, Woolven JM, Demont EH J Med Chem. 2021 Jul 7. doi: 10.1021/acs.jmedchem.0c02155. PMID:34232650<ref>PMID:34232650</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7nq3" 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

OCA — Wed, 21 Jul 2021 08:59:29 GMT

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

-	~~The entry 7nq3 is ON HOLD until Paper Publication~~	+	==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N4-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-6-((S)-methoxy(phenyl)methyl)-N2-methylpyridine-2,4-dicarboxamide==
-		+	<StructureSection load='7nq3' size='340' side='right'caption='[[7nq3]]' 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=7NQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NQ3 FirstGlance]. <br>
-	~~Description:~~ C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N4-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-6-((S)-methoxy(phenyl)methyl)-N2-methylpyridine-2,4-dicarboxamide	+	</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=7nq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nq3 OCA], [https://pdbe.org/7nq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nq3 RCSB], [https://www.ebi.ac.uk/pdbsum/7nq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nq3 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Chung, C]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Chung C]]

OCA at 09:29, 31 March 2021

OCA — Wed, 31 Mar 2021 09:29:46 GMT

←Older revision		Revision as of 09:29, 31 March 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7nq3 is ON HOLD	+	The entry 7nq3 is ON HOLD until Paper Publication

	Authors: Chung, C.		Authors: Chung, C.

OCA: Protected "7nq3" [edit=sysop:move=sysop]

OCA — Wed, 10 Mar 2021 15:03:08 GMT

Protected "7nq3" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:03, 10 March 2021

OCA: New page: '''Unreleased structure''' The entry 7nq3 is ON HOLD Authors: Chung, C. Description: C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N4-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-6-((S)-meth...

OCA — Wed, 10 Mar 2021 15:03:06 GMT

New page: '''Unreleased structure''' The entry 7nq3 is ON HOLD Authors: Chung, C. Description: C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N4-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-6-((S)-meth...

New page

'''Unreleased structure'''

The entry 7nq3 is ON HOLD

Authors: Chung, C.

Description: C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N4-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-6-((S)-methoxy(phenyl)methyl)-N2-methylpyridine-2,4-dicarboxamide
[[Category: Unreleased Structures]]
[[Category: Chung, C]]