5h21 - Revision history

OCA at 09:14, 20 March 2024

OCA — Wed, 20 Mar 2024 09:14:43 GMT

←Older revision		Revision as of 09:14, 20 March 2024
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	== Function ==		== Function ==
	[https://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 ==
-	As a member of the bromodomain and extra terminal domain (BET) protein family, BRD4 is closely related to cancers and other diseases. Small-molecule BRD4 inhibitors have already demonstrated promising potential for the therapy of BRD4-related cancers. In this study, we report the discovery and evaluation of a novel category of BRD4 inhibitors, which share a trimethoxy ring and target the first bromodomain of the human BRD4 protein. The IC50 value of the most potent compound, DC-BD-03, is 2.01 muM. In addition, a high-resolution crystal structure of the compound DC-BD-29 with the first bromodomain of BRD4 was determined, which revealed the binding mode and facilitated further structure-based optimization. These compounds exhibited anti-proliferation activity, caused cell cycle arrest, and induced apoptosis in human leukemia MV4-11 cells. Thus, the results presented in this study indicated the potential of this series of compounds as drug candidates for the therapy of BRD4-related cancers.
-
-	Discovery of novel trimethoxy-ring BRD4 bromodomain inhibitors: AlphaScreen assay, crystallography and cell-based assay.,Chen Z, Zhang H, Liu S, Xie Y, Jiang H, Lu W, Xu H, Yue L, Zhang Y, Ding H, Zheng M, Yu K, Chen K, Jiang H, Luo C Medchemcomm. 2017 Mar 17;8(6):1322-1331. doi: 10.1039/c7md00083a. eCollection, 2017 Jun 1. PMID:30108844<ref>PMID:30108844</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5h21" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 07:21, 9 August 2023

OCA — Wed, 09 Aug 2023 07:21:23 GMT

←Older revision		Revision as of 07:21, 9 August 2023
Line 3:		Line 3:
	<StructureSection load='5h21' size='340' side='right'caption='[[5h21]], [[Resolution\|resolution]] 1.59Å' scene=''>		<StructureSection load='5h21' size='340' side='right'caption='[[5h21]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5h21]] 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=5H21 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5H21 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5h21]] 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=5H21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H21 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=RMR:3~~,~~4,5-trimethoxy-~{N}-(2-thiophen-2-ylethyl)benzamide'>RMR</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]] 1.591Å</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=RMR:3,4,5-trimethoxy-~{N}-(2-thiophen-2-ylethyl)benzamide'>RMR</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=5h21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h21 OCA], [~~http~~://pdbe.org/5h21 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5h21 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5h21 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5h21 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=5h21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h21 OCA], [https://pdbe.org/5h21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h21 RCSB], [https://www.ebi.ac.uk/pdbsum/5h21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h21 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Luo, C]]	+	[[Category: Luo C]]
-	[[Category: Zhang, H]]	+	[[Category: Zhang H]]
-	~~[[Category: Brd4]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Peptide binding protein-inhibitor complex~~]]	+

OCA at 11:39, 25 December 2019

OCA — Wed, 25 Dec 2019 11:39:31 GMT

←Older revision		Revision as of 11:39, 25 December 2019
Line 1:		Line 1:

	==Trimethoxy-ring inhibitor in complex with the first bromodomain of BRD4==		==Trimethoxy-ring inhibitor in complex with the first bromodomain of BRD4==
-	<StructureSection load='5h21' size='340' side='right' caption='[[5h21]], [[Resolution\|resolution]] 1.59Å' scene=''>	+	<StructureSection load='5h21' size='340' side='right'caption='[[5h21]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5h21]] 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=5H21 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H21 FirstGlance]. <br>		<table><tr><td colspan='2'>[[5h21]] 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=5H21 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H21 FirstGlance]. <br>
Line 12:		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 ==
		+	As a member of the bromodomain and extra terminal domain (BET) protein family, BRD4 is closely related to cancers and other diseases. Small-molecule BRD4 inhibitors have already demonstrated promising potential for the therapy of BRD4-related cancers. In this study, we report the discovery and evaluation of a novel category of BRD4 inhibitors, which share a trimethoxy ring and target the first bromodomain of the human BRD4 protein. The IC50 value of the most potent compound, DC-BD-03, is 2.01 muM. In addition, a high-resolution crystal structure of the compound DC-BD-29 with the first bromodomain of BRD4 was determined, which revealed the binding mode and facilitated further structure-based optimization. These compounds exhibited anti-proliferation activity, caused cell cycle arrest, and induced apoptosis in human leukemia MV4-11 cells. Thus, the results presented in this study indicated the potential of this series of compounds as drug candidates for the therapy of BRD4-related cancers.
		+
		+	Discovery of novel trimethoxy-ring BRD4 bromodomain inhibitors: AlphaScreen assay, crystallography and cell-based assay.,Chen Z, Zhang H, Liu S, Xie Y, Jiang H, Lu W, Xu H, Yue L, Zhang Y, Ding H, Zheng M, Yu K, Chen K, Jiang H, Luo C Medchemcomm. 2017 Mar 17;8(6):1322-1331. doi: 10.1039/c7md00083a. eCollection, 2017 Jun 1. PMID:30108844<ref>PMID:30108844</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5h21" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 17:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Luo, C]]		[[Category: Luo, C]]
	[[Category: Zhang, H]]		[[Category: Zhang, H]]

OCA at 06:24, 16 November 2017

OCA — Thu, 16 Nov 2017 06:24:47 GMT

←Older revision		Revision as of 06:24, 16 November 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5h21 is ~~ON HOLD until Paper Publication~~	+	==Trimethoxy-ring inhibitor in complex with the first bromodomain of BRD4==
-		+	<StructureSection load='5h21' size='340' side='right' caption='[[5h21]], [[Resolution\|resolution]] 1.59Å' scene=''>
-	~~Authors~~: ~~Zhang~~, H., ~~Luo~~, C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5h21]] 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=5H21 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H21 FirstGlance]. <br>
-	~~Description~~: ~~Trimethoxy-ring inhibitor~~ in ~~complex with the first bromodomain~~ of BRD4	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RMR:3,4,5-trimethoxy-~{N}-(2-thiophen-2-ylethyl)benzamide'>RMR</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=5h21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h21 OCA], [http://pdbe.org/5h21 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h21 RCSB], [http://www.ebi.ac.uk/pdbsum/5h21 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h21 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).
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Luo, C]]
	[[Category: Zhang, H]]		[[Category: Zhang, H]]
-	[[Category: ~~Luo, C~~]]	+	[[Category: Brd4]]
		+	[[Category: Inhibitor]]
		+	[[Category: Peptide binding protein-inhibitor complex]]

OCA at 13:39, 9 December 2016

OCA — Fri, 09 Dec 2016 13:39:11 GMT

←Older revision		Revision as of 13:39, 9 December 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5h21 is ON HOLD	+	The entry 5h21 is ON HOLD until Paper Publication

	Authors: Zhang, H., Luo, C.		Authors: Zhang, H., Luo, C.

OCA at 13:14, 26 October 2016

OCA — Wed, 26 Oct 2016 13:14:17 GMT

←Older revision		Revision as of 13:14, 26 October 2016
Line 5:		Line 5:
	Authors: Zhang, H., Luo, C.		Authors: Zhang, H., Luo, C.

-	Description: ~~trimethoxy~~-ring inhibitor in complex with the first bromodomain of BRD4	+	Description: Trimethoxy-ring inhibitor in complex with the first bromodomain of BRD4
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Zhang, H]]		[[Category: Zhang, H]]
	[[Category: Luo, C]]		[[Category: Luo, C]]

OCA: Protected "5h21" [edit=sysop:move=sysop]

OCA — Wed, 19 Oct 2016 12:03:45 GMT

Protected "5h21" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:03, 19 October 2016

OCA: New page: '''Unreleased structure''' The entry 5h21 is ON HOLD Authors: Zhang, H., Luo, C. Description: trimethoxy-ring inhibitor in complex with the first bromodomain of BRD4 [[Category: Unrele...

OCA — Wed, 19 Oct 2016 12:03:44 GMT

New page: '''Unreleased structure''' The entry 5h21 is ON HOLD Authors: Zhang, H., Luo, C. Description: trimethoxy-ring inhibitor in complex with the first bromodomain of BRD4 [[Category: Unrele...

New page

'''Unreleased structure'''

The entry 5h21 is ON HOLD

Authors: Zhang, H., Luo, C.

Description: trimethoxy-ring inhibitor in complex with the first bromodomain of BRD4
[[Category: Unreleased Structures]]
[[Category: Zhang, H]]
[[Category: Luo, C]]