5z1r - Revision history

OCA at 10:26, 27 March 2024

OCA — Wed, 27 Mar 2024 10:26:20 GMT

←Older revision		Revision as of 10:26, 27 March 2024
Line 3:		Line 3:
	<StructureSection load='5z1r' size='340' side='right'caption='[[5z1r]], [[Resolution\|resolution]] 1.62Å' scene=''>		<StructureSection load='5z1r' size='340' side='right'caption='[[5z1r]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z1r]] 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=5Z1R OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5Z1R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z1r]] 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=5Z1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z1R FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EFL:5-bromo-N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2-methoxybenzene-1-sulfonamide'>EFL</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EFL:5-bromo-N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2-methoxybenzene-1-sulfonamide'>EFL</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=5z1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1r OCA], [~~http~~://pdbe.org/5z1r PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5z1r RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5z1r PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1r 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=5z1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1r OCA], [https://pdbe.org/5z1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z1r RCSB], [https://www.ebi.ac.uk/pdbsum/5z1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1r 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 ==~~	+
-	Prostate cancer is a commonly diagnosed cancer and a leading cause of cancer-related deaths. The bromodomain and extra terminal domain (BET) family proteins have emerged as potential therapeutic targets for the treatment of castration-resistant prostate cancer. A series of 2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives were designed and synthesized as selective bromodomain containing protein 4 (BRD4) inhibitors. The compounds potently inhibit BRD4(1) with nanomolar IC50 values and exhibit high selectivity over most non-BET subfamily members. One of the representative compounds 36 (Y08060) effectively suppresses cell growth, colony formation, and expression of androgen receptor (AR), AR regulated genes, and MYC in prostate cancer cell lines. In in vivo studies, 36 demonstrates a good PK profile with high oral bioavailability (61.54%) and is a promising lead compound for further prostate cancer drug development.	+
-		+
-	Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer.,Xiang Q, Zhang Y, Li J, Xue X, Wang C, Song M, Zhang C, Wang R, Li C, Wu C, Zhou Y, Yang X, Li G, Ding K, Xu Y ACS Med Chem Lett. 2018 Feb 13;9(3):262-267. doi: 10.1021/acsmedchemlett.8b00003., eCollection 2018 Mar 8. PMID:29541371<ref>PMID:29541371</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5z1r" 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: Xiang, Q]]	+	[[Category: Xiang Q]]
-	[[Category: Xu, Y]]	+	[[Category: Xu Y]]
-	[[Category: Zhang, Y]]	+	[[Category: Zhang Y]]
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 08:31, 24 July 2019

OCA — Wed, 24 Jul 2019 08:31:45 GMT

←Older revision		Revision as of 08:31, 24 July 2019
Line 1:		Line 1:

	==Crystal Structure Analysis of the BRD4==		==Crystal Structure Analysis of the BRD4==
-	<StructureSection load='5z1r' size='340' side='right' caption='[[5z1r]], [[Resolution\|resolution]] 1.62Å' scene=''>	+	<StructureSection load='5z1r' size='340' side='right'caption='[[5z1r]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z1r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z1R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z1r]] 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=5Z1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z1R FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EFL:5-bromo-N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2-methoxybenzene-1-sulfonamide'>EFL</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EFL:5-bromo-N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2-methoxybenzene-1-sulfonamide'>EFL</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=5z1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1r OCA], [http://pdbe.org/5z1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z1r RCSB], [http://www.ebi.ac.uk/pdbsum/5z1r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1r 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=5z1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1r OCA], [http://pdbe.org/5z1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z1r RCSB], [http://www.ebi.ac.uk/pdbsum/5z1r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1r ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).		[[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 ==
		+	Prostate cancer is a commonly diagnosed cancer and a leading cause of cancer-related deaths. The bromodomain and extra terminal domain (BET) family proteins have emerged as potential therapeutic targets for the treatment of castration-resistant prostate cancer. A series of 2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives were designed and synthesized as selective bromodomain containing protein 4 (BRD4) inhibitors. The compounds potently inhibit BRD4(1) with nanomolar IC50 values and exhibit high selectivity over most non-BET subfamily members. One of the representative compounds 36 (Y08060) effectively suppresses cell growth, colony formation, and expression of androgen receptor (AR), AR regulated genes, and MYC in prostate cancer cell lines. In in vivo studies, 36 demonstrates a good PK profile with high oral bioavailability (61.54%) and is a promising lead compound for further prostate cancer drug development.
		+
		+	Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer.,Xiang Q, Zhang Y, Li J, Xue X, Wang C, Song M, Zhang C, Wang R, Li C, Wu C, Zhou Y, Yang X, Li G, Ding K, Xu Y ACS Med Chem Lett. 2018 Feb 13;9(3):262-267. doi: 10.1021/acsmedchemlett.8b00003., eCollection 2018 Mar 8. PMID:29541371<ref>PMID:29541371</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5z1r" 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 06:06, 2 January 2019

OCA — Wed, 02 Jan 2019 06:06:08 GMT

←Older revision		Revision as of 06:06, 2 January 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5z1r ~~is ON HOLD until Paper Publication~~	+	==Crystal Structure Analysis of the BRD4==
-		+	<StructureSection load='5z1r' size='340' side='right' caption='[[5z1r]], [[Resolution\|resolution]] 1.62Å' scene=''>
-	~~Authors~~: ~~Xu, Y~~., ~~Zhang~~, Y., ~~Xiang~~, Q., ~~Song~~, M., ~~Wang~~, C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5z1r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z1R FirstGlance]. <br>
-	~~Description~~: ~~Crystal Structure Analysis~~ of ~~the~~ BRD4	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EFL:5-bromo-N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2-methoxybenzene-1-sulfonamide'>EFL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=5z1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1r OCA], [http://pdbe.org/5z1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z1r RCSB], [http://www.ebi.ac.uk/pdbsum/5z1r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1r ProSAT]</span></td></tr>
-	[[Category: ~~Zhang~~, Y]]	+	</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).
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Song, M]]
	[[Category: Wang, C]]		[[Category: Wang, C]]
	[[Category: Xiang, Q]]		[[Category: Xiang, Q]]
-	[[Category: Song, M]]
	[[Category: Xu, Y]]		[[Category: Xu, Y]]
		+	[[Category: Zhang, Y]]
		+	[[Category: Bromodomain]]
		+	[[Category: Transcription]]

OCA at 03:49, 20 June 2018

OCA — Wed, 20 Jun 2018 03:49:41 GMT

←Older revision		Revision as of 03:49, 20 June 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5z1r is ON HOLD	+	The entry 5z1r is ON HOLD until Paper Publication

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

OCA: Protected "5z1r" [edit=sysop:move=sysop]

OCA — Wed, 03 Jan 2018 04:52:40 GMT

Protected "5z1r" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:52, 3 January 2018

OCA: New page: '''Unreleased structure''' The entry 5z1r is ON HOLD Authors: Xu, Y., Zhang, Y., Xiang, Q., Song, M., Wang, C. Description: Crystal Structure Analysis of the BRD4 [[Category: Unrelease...

OCA — Wed, 03 Jan 2018 04:52:39 GMT

New page: '''Unreleased structure''' The entry 5z1r is ON HOLD Authors: Xu, Y., Zhang, Y., Xiang, Q., Song, M., Wang, C. Description: Crystal Structure Analysis of the BRD4 [[Category: Unrelease...

New page

'''Unreleased structure'''

The entry 5z1r is ON HOLD

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

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