7wni - Revision history

OCA at 17:42, 29 November 2023

OCA — Wed, 29 Nov 2023 17:42:44 GMT

←Older revision		Revision as of 17:42, 29 November 2023
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	==Crystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor Y13158==		==Crystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor Y13158==
-	<StructureSection load='7wni' size='340' side='right'caption='[[7wni]]' scene=''>	+	<StructureSection load='7wni' size='340' side='right'caption='[[7wni]], [[Resolution\|resolution]] 3.12Å' 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=7WNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WNI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7wni]] 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=7WNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WNI 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=7wni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wni OCA], [https://pdbe.org/7wni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wni RCSB], [https://www.ebi.ac.uk/pdbsum/7wni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wni ProSAT]</span></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]] 3.12Å</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=JGU:7-[2-[2,4-bis(fluoranyl)phenoxy]-5-(2-oxidanylpropan-2-yl)phenyl]-2-[4-(2-hydroxyethyloxy)-3,5-dimethyl-phenyl]-5-methyl-furo[3,2-c]pyridin-4-one'>JGU</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=7wni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wni OCA], [https://pdbe.org/7wni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wni RCSB], [https://www.ebi.ac.uk/pdbsum/7wni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wni 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 ==
		+	Pan-bromodomain and extra terminal (Pan-BET) inhibitors show profound efficacy but exhibit pharmacology-driven toxicities in clinical trials. The development of domain-selective BET inhibitors to separate efficacy and toxicity is urgently needed. Herein, we report a series of furo[3,2-c]pyridin-4(5H)-one derivatives as novel BD2-selective BET inhibitors. The representative compound 8l (XY153) potently bound to BRD4 BD2 with an half-maximum inhibitory concentration (IC50) value of 0.79 nM and displayed 354-fold selectivity over BRD4 BD1. Besides, 8l exhibited 6-fold BRD4 BD2 domain selectivity over other BET BD2 domains. Compound 8l displayed potent antiproliferative activity against multiple tumor cell lines, especially MV4-11 (IC50 = 0.55 nM), while showing weak cytotoxicity against the normal lung fibroblast cell line. It highlights the safety profile of this series of BD2 inhibitors. 8l also demonstrated good metabolic stability in vitro. These data indicate that 8l may serve as a new and valuable lead compound for the development of potential therapeutics against acute myeloid leukemia (AML).
		+
		+	Structure-Based Discovery and Optimization of Furo[3,2-c]pyridin-4(5H)-one Derivatives as Potent and Second Bromodomain (BD2)-Selective Bromo and Extra Terminal Domain (BET) Inhibitors.,Li J, Zhang C, Xu H, Wang C, Dong R, Shen H, Zhuang X, Chen X, Li Q, Lu J, Zhang M, Wu X, Loomes KM, Zhou Y, Zhang Y, Liu J, Xu Y J Med Chem. 2022 Apr 14;65(7):5760-5799. doi: 10.1021/acs.jmedchem.2c00100. Epub , 2022 Mar 25. PMID:35333526<ref>PMID:35333526</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7wni" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Li J]]		[[Category: Li J]]

OCA at 05:02, 10 August 2022

OCA — Wed, 10 Aug 2022 05:02:04 GMT

←Older revision		Revision as of 05:02, 10 August 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7wni ~~is ON HOLD until Paper Publication~~	+	==Crystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor Y13158==
-		+	<StructureSection load='7wni' size='340' side='right'caption='[[7wni]]' scene=''>
-	~~Authors~~: ~~Li, J~~.~~, Zhang, C~~., ~~Xu, H~~., ~~Zhuang, X~~., ~~Wu, X~~., ~~Zhang, Y~~., ~~Xu, Y~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WNI FirstGlance]. <br>
-	~~Description: Crystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor Y13158~~	+	</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=7wni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wni OCA], [https://pdbe.org/7wni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wni RCSB], [https://www.ebi.ac.uk/pdbsum/7wni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wni ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Zhang, Y~~]]	+	__TOC__
-	[[Category: Wu, X]]	+	</StructureSection>
-	[[Category: ~~Zhuang, X~~]]	+	[[Category: Large Structures]]
-	[[Category: Xu~~, H~~]]	+	[[Category: Li J]]
-	[[Category: ~~Li, J~~]]	+	[[Category: Wu X]]
-	[[Category: Zhang~~, C~~]]	+	[[Category: Xu H]]
-	[[Category: ~~Xu, Y~~]]	+	[[Category: Xu Y]]
		+	[[Category: Zhang C]]
		+	[[Category: Zhang Y]]
		+	[[Category: Zhuang X]]

OCA at 05:11, 2 March 2022

OCA — Wed, 02 Mar 2022 05:11:31 GMT

←Older revision		Revision as of 05:11, 2 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Li, J., Zhang, C., Xu, H., Zhuang, X., Wu, X., Zhang, Y., Xu, Y.		Authors: Li, J., Zhang, C., Xu, H., Zhuang, X., Wu, X., Zhang, Y., Xu, Y.
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	Description: Crystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor Y13158		Description: Crystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor Y13158
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Zhang, Y]]
	[[Category: Wu, X]]		[[Category: Wu, X]]
	[[Category: Zhuang, X]]		[[Category: Zhuang, X]]
-	[[Category: Li, J]]
-	[[Category: Xu, Y]]
-	[[Category: Zhang, Y]]
	[[Category: Xu, H]]		[[Category: Xu, H]]
		+	[[Category: Li, J]]
	[[Category: Zhang, C]]		[[Category: Zhang, C]]
		+	[[Category: Xu, Y]]

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

OCA — Thu, 27 Jan 2022 05:47:04 GMT

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

←Older revision

Revision as of 05:47, 27 January 2022

OCA: New page: '''Unreleased structure''' The entry 7wni is ON HOLD Authors: Li, J., Zhang, C., Xu, H., Zhuang, X., Wu, X., Zhang, Y., Xu, Y. Description: Crystal Structure of the second bromodomain ...

OCA — Thu, 27 Jan 2022 05:47:03 GMT

New page: '''Unreleased structure''' The entry 7wni is ON HOLD Authors: Li, J., Zhang, C., Xu, H., Zhuang, X., Wu, X., Zhang, Y., Xu, Y. Description: Crystal Structure of the second bromodomain ...

New page

'''Unreleased structure'''

The entry 7wni is ON HOLD

Authors: Li, J., Zhang, C., Xu, H., Zhuang, X., Wu, X., Zhang, Y., Xu, Y.

Description: Crystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor Y13158
[[Category: Unreleased Structures]]
[[Category: Wu, X]]
[[Category: Zhuang, X]]
[[Category: Li, J]]
[[Category: Xu, Y]]
[[Category: Zhang, Y]]
[[Category: Xu, H]]
[[Category: Zhang, C]]