5y93 - Revision history

OCA at 10:22, 27 March 2024

OCA — Wed, 27 Mar 2024 10:22:16 GMT

←Older revision		Revision as of 10:22, 27 March 2024
Line 3:		Line 3:
	<StructureSection load='5y93' size='340' side='right'caption='[[5y93]], [[Resolution\|resolution]] 1.62Å' scene=''>		<StructureSection load='5y93' size='340' side='right'caption='[[5y93]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5y93]] 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=5Y93 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5Y93 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5y93]] 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=5Y93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y93 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8Q9:2-[[5-[(5-bromanyl-2-methoxy-phenyl)sulfonylamino]-3-methyl-1,2-benzoxazol-6-yl]oxy]-N-(2-morpholin-4-ylethyl)ethanamide'>8Q9</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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]] 1.62Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8Q9:2-[[5-[(5-bromanyl-2-methoxy-phenyl)sulfonylamino]-3-methyl-1,2-benzoxazol-6-yl]oxy]-N-(2-morpholin-4-ylethyl)ethanamide'>8Q9</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></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=5y93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y93 OCA], [~~http~~://pdbe.org/5y93 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5y93 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5y93 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5y93 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=5y93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y93 OCA], [https://pdbe.org/5y93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y93 RCSB], [https://www.ebi.ac.uk/pdbsum/5y93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y93 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>	+	[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).	+	[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The bromodomain and extra-terminal (BET) family proteins have gained increasing interest as drug targets for treatment of castration-resistant prostate cancer (CRPC). Here, we describe the design, optimization, and evaluation of benzo[ d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal structures of the representative inhibitors in complex with BRD4(1) provided solid structural basis for compound optimization. The two most potent compounds, 6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of 82 and 81 nM, respectively. They also exhibited high selectivity over other non-BET subfamily members. The compounds potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. These potent and selective BET inhibitors represent a new class of compounds for the development of potential therapeutics against CRPC.	+
-		+
-	Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC).,Zhang M, Zhang Y, Song M, Xue X, Wang J, Wang C, Zhang C, Li C, Xiang Q, Zou L, Wu X, Wu C, Dong B, Xue W, Zhou Y, Chen H, Wu D, Ding K, Xu Y J Med Chem. 2018 Apr 12;61(7):3037-3058. doi: 10.1021/acs.jmedchem.8b00103. Epub , 2018 Apr 3. PMID:29566488<ref>PMID:29566488</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5y93" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 28:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Song, M]]	+	[[Category: Song M]]
-	[[Category: Wang, C]]	+	[[Category: Wang C]]
-	[[Category: Xu, Y]]	+	[[Category: Xu Y]]
-	[[Category: Zhang, Y]]	+	[[Category: Zhang Y]]
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 09:44, 4 December 2019

OCA — Wed, 04 Dec 2019 09:44:58 GMT

←Older revision		Revision as of 09:44, 4 December 2019
Line 1:		Line 1:

	==Crystal Structure Analysis of the BRD4==		==Crystal Structure Analysis of the BRD4==
-	<StructureSection load='5y93' size='340' side='right' caption='[[5y93]], [[Resolution\|resolution]] 1.62Å' scene=''>	+	<StructureSection load='5y93' size='340' side='right'caption='[[5y93]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5y93]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y93 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5y93]] 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=5Y93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y93 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8Q9:2-[[5-[(5-bromanyl-2-methoxy-phenyl)sulfonylamino]-3-methyl-1,2-benzoxazol-6-yl]oxy]-N-(2-morpholin-4-ylethyl)ethanamide'>8Q9</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8Q9:2-[[5-[(5-bromanyl-2-methoxy-phenyl)sulfonylamino]-3-methyl-1,2-benzoxazol-6-yl]oxy]-N-(2-morpholin-4-ylethyl)ethanamide'>8Q9</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5y93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y93 OCA], [http://pdbe.org/5y93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y93 RCSB], [http://www.ebi.ac.uk/pdbsum/5y93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y93 ProSAT]</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=5y93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y93 OCA], [http://pdbe.org/5y93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y93 RCSB], [http://www.ebi.ac.uk/pdbsum/5y93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y93 ProSAT]</span></td></tr>
	</table>		</table>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5y93" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5y93" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Song, M]]		[[Category: Song, M]]
	[[Category: Wang, C]]		[[Category: Wang, C]]

OCA at 07:35, 14 June 2018

OCA — Thu, 14 Jun 2018 07:35:41 GMT

←Older revision		Revision as of 07:35, 14 June 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5y93 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure Analysis of the BRD4==
		+	<StructureSection load='5y93' size='340' side='right' caption='[[5y93]], [[Resolution\|resolution]] 1.62Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5y93]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y93 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8Q9:2-[[5-[(5-bromanyl-2-methoxy-phenyl)sulfonylamino]-3-methyl-1,2-benzoxazol-6-yl]oxy]-N-(2-morpholin-4-ylethyl)ethanamide'>8Q9</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></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=5y93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y93 OCA], [http://pdbe.org/5y93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y93 RCSB], [http://www.ebi.ac.uk/pdbsum/5y93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y93 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The bromodomain and extra-terminal (BET) family proteins have gained increasing interest as drug targets for treatment of castration-resistant prostate cancer (CRPC). Here, we describe the design, optimization, and evaluation of benzo[ d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal structures of the representative inhibitors in complex with BRD4(1) provided solid structural basis for compound optimization. The two most potent compounds, 6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of 82 and 81 nM, respectively. They also exhibited high selectivity over other non-BET subfamily members. The compounds potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. These potent and selective BET inhibitors represent a new class of compounds for the development of potential therapeutics against CRPC.

-	~~Authors: Xu, Y~~., Zhang, Y., Song, M., Wang, C.	+	Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC).,Zhang M, Zhang Y, Song M, Xue X, Wang J, Wang C, Zhang C, Li C, Xiang Q, Zou L, Wu X, Wu C, Dong B, Xue W, Zhou Y, Chen H, Wu D, Ding K, Xu Y J Med Chem. 2018 Apr 12;61(7):3037-3058. doi: 10.1021/acs.jmedchem.8b00103. Epub , 2018 Apr 3. PMID:29566488<ref>PMID:29566488</ref>

-	~~Description: Crystal Structure Analysis~~ of the ~~BRD4~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Xu, Y]]~~	+	<div class="pdbe-citations 5y93" style="background-color:#fffaf0;"></div>
-	~~[[Category: Zhang, Y]]~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Song, M]]		[[Category: Song, M]]
	[[Category: Wang, C]]		[[Category: Wang, C]]
		+	[[Category: Xu, Y]]
		+	[[Category: Zhang, Y]]
		+	[[Category: Bromodomain]]
		+	[[Category: Transcription]]

OCA: Protected "5y93" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 16:17:10 GMT

Protected "5y93" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:17, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5y93 is ON HOLD until Paper Publication Authors: Xu, Y., Zhang, Y., Song, M., Wang, C. Description: Crystal Structure Analysis of the BRD4 [[Catego...

OCA — Wed, 27 Sep 2017 16:17:09 GMT

New page: '''Unreleased structure''' The entry 5y93 is ON HOLD until Paper Publication Authors: Xu, Y., Zhang, Y., Song, M., Wang, C. Description: Crystal Structure Analysis of the BRD4 [[Catego...

New page

'''Unreleased structure'''

The entry 5y93 is ON HOLD until Paper Publication

Authors: Xu, Y., Zhang, Y., Song, M., Wang, C.

Description: Crystal Structure Analysis of the BRD4
[[Category: Unreleased Structures]]
[[Category: Xu, Y]]
[[Category: Zhang, Y]]
[[Category: Song, M]]
[[Category: Wang, C]]