4bw1 - Revision history

OCA at 11:06, 9 May 2024

OCA — Thu, 09 May 2024 11:06:07 GMT

←Older revision		Revision as of 11:06, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bw1]] 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=4BW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BW1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bw1]] 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=4BW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BW1 FirstGlance]. <br>
-	</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=S5B:4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC+ACID'>S5B</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]] 1.4Å</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=S5B:4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC+ACID'>S5B</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=4bw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw1 OCA], [https://pdbe.org/4bw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bw1 RCSB], [https://www.ebi.ac.uk/pdbsum/4bw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw1 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=4bw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw1 OCA], [https://pdbe.org/4bw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bw1 RCSB], [https://www.ebi.ac.uk/pdbsum/4bw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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>	+	[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 ==
-	[[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 ==
		+	Bromodomains (BRDs) are small protein domains found in a variety of proteins that recognize and bind to acetylated histone tails. This binding affects chromatin structure and facilitates the localisation of transcriptional complexes to specific genes, thereby regulating epigenetically controlled processes including gene transcription and mRNA elongation. Inhibitors of the bromodomain and extra-terminal (BET) proteins BRD2-4 and T, which prevent bromodomain binding to acetyl-modified histone tails, have shown therapeutic promise in several diseases. We report here the discovery of 1,5-naphthyridine derivatives as potent inhibitors of the BET bromodomain family with good cell activity and oral pharmacokinetic parameters. X-ray crystal structures of naphthyridine isomers have been solved and quantum mechanical calculations have been used to explain the higher affinity of the 1,5-isomer over the others. The best compounds were progressed in a mouse model of inflammation and exhibited dose-dependent anti-inflammatory pharmacology.
		+
		+	Naphthyridines as Novel BET Family Bromodomain Inhibitors.,Mirguet O, Lamotte Y, Chung CW, Bamborough P, Delannee D, Bouillot A, Gellibert F, Krysa G, Lewis A, Witherington J, Huet P, Dudit Y, Trottet L, Nicodeme E ChemMedChem. 2013 Sep 2. doi: 10.1002/cmdc.201300259. PMID:24000170<ref>PMID:24000170</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4bw1" style="background-color:#fffaf0;"></div>

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

OCA at 17:11, 7 September 2022

OCA — Wed, 07 Sep 2022 17:11:56 GMT

←Older revision		Revision as of 17:11, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4bw1' size='340' side='right'caption='[[4bw1]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4bw1' size='340' side='right'caption='[[4bw1]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bw1]] 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=4BW1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BW1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bw1]] 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=4BW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BW1 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=S5B:4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC+ACID'>S5B</scene>~~</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=S5B:4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC+ACID'>S5B</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bw2\|4bw2]], [[4bw3\|4bw3]], [[4bw4\|4bw4]]~~</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=4bw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw1 OCA], [https://pdbe.org/4bw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bw1 RCSB], [https://www.ebi.ac.uk/pdbsum/4bw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw1 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=4bw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw1 OCA], [~~http~~://pdbe.org/4bw1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4bw1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4bw1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw1 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 ==~~	+
-	Bromodomains (BRDs) are small protein domains found in a variety of proteins that recognize and bind to acetylated histone tails. This binding affects chromatin structure and facilitates the localisation of transcriptional complexes to specific genes, thereby regulating epigenetically controlled processes including gene transcription and mRNA elongation. Inhibitors of the bromodomain and extra-terminal (BET) proteins BRD2-4 and T, which prevent bromodomain binding to acetyl-modified histone tails, have shown therapeutic promise in several diseases. We report here the discovery of 1,5-naphthyridine derivatives as potent inhibitors of the BET bromodomain family with good cell activity and oral pharmacokinetic parameters. X-ray crystal structures of naphthyridine isomers have been solved and quantum mechanical calculations have been used to explain the higher affinity of the 1,5-isomer over the others. The best compounds were progressed in a mouse model of inflammation and exhibited dose-dependent anti-inflammatory pharmacology.	+
-		+
-	Naphthyridines as Novel BET Family Bromodomain Inhibitors.,Mirguet O, Lamotte Y, Chung CW, Bamborough P, Delannee D, Bouillot A, Gellibert F, Krysa G, Lewis A, Witherington J, Huet P, Dudit Y, Trottet L, Nicodeme E ChemMedChem. 2013 Sep 2. doi: 10.1002/cmdc.201300259. PMID:24000170<ref>PMID:24000170</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4bw1" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
-	*[[Bromodomain-containing protein\|Bromodomain-containing protein]]	+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bamborough, P]]	+	[[Category: Bamborough P]]
-	[[Category: Bouillot, A]]	+	[[Category: Bouillot A]]
-	[[Category: Chung, C]]	+	[[Category: Chung C]]
-	[[Category: Delannee, D]]	+	[[Category: Delannee D]]
-	[[Category: Dudit, Y]]	+	[[Category: Dudit Y]]
-	[[Category: Gellibert, F]]	+	[[Category: Gellibert F]]
-	[[Category: Huet, P]]	+	[[Category: Huet P]]
-	[[Category: Krysa, G]]	+	[[Category: Krysa G]]
-	[[Category: Lamotte, Y]]	+	[[Category: Lamotte Y]]
-	[[Category: Lewis, A]]	+	[[Category: Lewis A]]
-	[[Category: Mirguet, O]]	+	[[Category: Mirguet O]]
-	[[Category: Nicodeme, E]]	+	[[Category: Nicodeme E]]
-	[[Category: Trottet, L]]	+	[[Category: Trottet L]]
-	[[Category: Witherington, J]]	+	[[Category: Witherington J]]
-	~~[[Category: Antagonist]]~~	+
-	~~[[Category: Epigenetic reader]]~~	+
-	~~[[Category: Histone]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 13:50, 13 March 2019

OCA — Wed, 13 Mar 2019 13:50:38 GMT

←Older revision		Revision as of 13:50, 13 March 2019
Line 1:		Line 1:

	==The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand==		==The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand==
-	<StructureSection load='4bw1' size='340' side='right' caption='[[4bw1]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='4bw1' size='340' side='right'caption='[[4bw1]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bw1]] 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=4BW1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BW1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bw1]] 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=4BW1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BW1 FirstGlance]. <br>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bamborough, P]]		[[Category: Bamborough, P]]
	[[Category: Bouillot, A]]		[[Category: Bouillot, A]]

OCA at 17:28, 11 August 2016

OCA — Thu, 11 Aug 2016 17:28:30 GMT

←Older revision		Revision as of 17:28, 11 August 2016
Line 1:		Line 1:
		+
	==The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand==		==The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand==
	<StructureSection load='4bw1' size='340' side='right' caption='[[4bw1]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4bw1' size='340' side='right' caption='[[4bw1]], [[Resolution\|resolution]] 1.40Å' scene=''>
Line 5:		Line 6:
	</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=S5B:4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC+ACID'>S5B</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=S5B:4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC+ACID'>S5B</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bw2\|4bw2]], [[4bw3\|4bw3]], [[4bw4\|4bw4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bw2\|4bw2]], [[4bw3\|4bw3]], [[4bw4\|4bw4]]</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=4bw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bw1 RCSB], [http://www.ebi.ac.uk/pdbsum/4bw1 PDBsum]</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=4bw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw1 OCA], [http://pdbe.org/4bw1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bw1 RCSB], [http://www.ebi.ac.uk/pdbsum/4bw1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bw1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4bw1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein\|Bromodomain-containing protein]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:22, 4 January 2015

OCA — Sun, 04 Jan 2015 14:22:55 GMT

←Older revision		Revision as of 14:22, 4 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4bw1\| PDB=4bw1 \| SCENE= }}~~	+	==The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand==
-	===The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand===	+	<StructureSection load='4bw1' size='340' side='right' caption='[[4bw1]], [[Resolution\|resolution]] 1.40Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24000170}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4bw1]] 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=4BW1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BW1 FirstGlance]. <br>
-	==Disease==	+	</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=S5B:4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC+ACID'>S5B</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bw2\|4bw2]], [[4bw3\|4bw3]], [[4bw4\|4bw4]]</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=4bw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bw1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bw1 RCSB], [http://www.ebi.ac.uk/pdbsum/4bw1 PDBsum]</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>		[[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 ==
-	==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 ==
		+	Bromodomains (BRDs) are small protein domains found in a variety of proteins that recognize and bind to acetylated histone tails. This binding affects chromatin structure and facilitates the localisation of transcriptional complexes to specific genes, thereby regulating epigenetically controlled processes including gene transcription and mRNA elongation. Inhibitors of the bromodomain and extra-terminal (BET) proteins BRD2-4 and T, which prevent bromodomain binding to acetyl-modified histone tails, have shown therapeutic promise in several diseases. We report here the discovery of 1,5-naphthyridine derivatives as potent inhibitors of the BET bromodomain family with good cell activity and oral pharmacokinetic parameters. X-ray crystal structures of naphthyridine isomers have been solved and quantum mechanical calculations have been used to explain the higher affinity of the 1,5-isomer over the others. The best compounds were progressed in a mouse model of inflammation and exhibited dose-dependent anti-inflammatory pharmacology.

-	~~==About this Structure==~~	+	Naphthyridines as Novel BET Family Bromodomain Inhibitors.,Mirguet O, Lamotte Y, Chung CW, Bamborough P, Delannee D, Bouillot A, Gellibert F, Krysa G, Lewis A, Witherington J, Huet P, Dudit Y, Trottet L, Nicodeme E ChemMedChem. 2013 Sep 2. doi: 10.1002/cmdc.201300259. PMID:24000170<ref>PMID:24000170</ref>
-	~~[[4bw1]] 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=4BW1 OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024000170</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Bamborough, P.]]	+	[[Category: Bamborough, P]]
-	[[Category: Bouillot, A.]]	+	[[Category: Bouillot, A]]
-	[[Category: Chung, C.]]	+	[[Category: Chung, C]]
-	[[Category: Delannee, D.]]	+	[[Category: Delannee, D]]
-	[[Category: Dudit, Y.]]	+	[[Category: Dudit, Y]]
-	[[Category: Gellibert, F.]]	+	[[Category: Gellibert, F]]
-	[[Category: Huet, P.]]	+	[[Category: Huet, P]]
-	[[Category: Krysa, G.]]	+	[[Category: Krysa, G]]
-	[[Category: Lamotte, Y.]]	+	[[Category: Lamotte, Y]]
-	[[Category: Lewis, A.]]	+	[[Category: Lewis, A]]
-	[[Category: Mirguet, O.]]	+	[[Category: Mirguet, O]]
-	[[Category: Nicodeme, E.]]	+	[[Category: Nicodeme, E]]
-	[[Category: Trottet, L.]]	+	[[Category: Trottet, L]]
-	[[Category: Witherington, J.]]	+	[[Category: Witherington, J]]
	[[Category: Antagonist]]		[[Category: Antagonist]]
	[[Category: Epigenetic reader]]		[[Category: Epigenetic reader]]

OCA at 09:49, 19 March 2014

OCA — Wed, 19 Mar 2014 09:49:44 GMT

←Older revision		Revision as of 09:49, 19 March 2014
Line 10:		Line 10:

	==About this Structure==		==About this Structure==
-	[[4bw1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BW1 OCA].	+	[[4bw1]] 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=4BW1 OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:024000170</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:024000170</ref><references group="xtra"/><references/>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Bamborough, P.]]		[[Category: Bamborough, P.]]
	[[Category: Bouillot, A.]]		[[Category: Bouillot, A.]]

OCA at 05:19, 12 September 2013

OCA — Thu, 12 Sep 2013 05:19:02 GMT

←Older revision		Revision as of 05:19, 12 September 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4bw1\| PDB=4bw1 \| SCENE= }}
		+	===The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand===
		+	{{ABSTRACT_PUBMED_24000170}}

-	~~The entry 4bw1~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==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>

-	~~Authors~~: ~~Chung, C~~.~~, Mirguet, O~~.~~, Lamotte, Y., Bamborough, P., Delannee, D., Bouillot, A., Gellibert, F., Krysa, G., Lewis, A., Witherington, J., Huet, P., Dudit, Y., Trottet, L., Nicodeme, E~~.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).

-	~~Description: The first bromodomain of human BRD4 in complex~~ with 3,~~5 dimethylisoxaxole ligand~~	+	==About this Structure==
		+	[[4bw1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BW1 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024000170</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Bamborough, P.]]
		+	[[Category: Bouillot, A.]]
		+	[[Category: Chung, C.]]
		+	[[Category: Delannee, D.]]
		+	[[Category: Dudit, Y.]]
		+	[[Category: Gellibert, F.]]
		+	[[Category: Huet, P.]]
		+	[[Category: Krysa, G.]]
		+	[[Category: Lamotte, Y.]]
		+	[[Category: Lewis, A.]]
		+	[[Category: Mirguet, O.]]
		+	[[Category: Nicodeme, E.]]
		+	[[Category: Trottet, L.]]
		+	[[Category: Witherington, J.]]
		+	[[Category: Antagonist]]
		+	[[Category: Epigenetic reader]]
		+	[[Category: Histone]]
		+	[[Category: Inhibitor]]
		+	[[Category: Transcription]]

OCA: Protected "4bw1" [edit=sysop:move=sysop]

OCA — Wed, 10 Jul 2013 14:45:43 GMT

Protected "4bw1" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:45, 10 July 2013

OCA: New page: '''Unreleased structure''' The entry 4bw1 is ON HOLD until Paper Publication Authors: Chung, C., Mirguet, O., Lamotte, Y., Bamborough, P., Delannee, D., Bouillot, A., Gellibert, F., Kry...

OCA — Wed, 10 Jul 2013 14:45:42 GMT

New page: '''Unreleased structure''' The entry 4bw1 is ON HOLD until Paper Publication Authors: Chung, C., Mirguet, O., Lamotte, Y., Bamborough, P., Delannee, D., Bouillot, A., Gellibert, F., Kry...

New page

'''Unreleased structure'''

The entry 4bw1 is ON HOLD until Paper Publication

Authors: Chung, C., Mirguet, O., Lamotte, Y., Bamborough, P., Delannee, D., Bouillot, A., Gellibert, F., Krysa, G., Lewis, A., Witherington, J., Huet, P., Dudit, Y., Trottet, L., Nicodeme, E.

Description: The first bromodomain of human BRD4 in complex with 3,5 dimethylisoxaxole ligand