4c66: Difference between revisions
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==Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains== | ==Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains== | ||
<StructureSection load='4c66' size='340' side='right' caption='[[4c66]], [[Resolution|resolution]] 1.87Å' scene=''> | <StructureSection load='4c66' size='340' side='right' caption='[[4c66]], [[Resolution|resolution]] 1.87Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4c66]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4c66]] 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=4C66 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C66 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H4C:4-(2-CHLOROPHENYL)-2-ETHYL-9-METHYL-6,8-DIHYDROTHIENO[3,2-F][1,2,4]TRIAZOLO[4,3-A][1,4]DIAZEPIN-10-IUM'>H4C</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H4C:4-(2-CHLOROPHENYL)-2-ETHYL-9-METHYL-6,8-DIHYDROTHIENO[3,2-F][1,2,4]TRIAZOLO[4,3-A][1,4]DIAZEPIN-10-IUM'>H4C</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c67|4c67]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c67|4c67]]</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=4c66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c66 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4c66 RCSB], [http://www.ebi.ac.uk/pdbsum/4c66 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=4c66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c66 OCA], [http://pdbe.org/4c66 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c66 RCSB], [http://www.ebi.ac.uk/pdbsum/4c66 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c66 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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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 4c66" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Bromodomain-containing protein|Bromodomain-containing protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Chung, C]] | [[Category: Chung, C]] | ||
[[Category: Mirguet, O]] | [[Category: Mirguet, O]] | ||
Revision as of 01:15, 5 August 2016
Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET BromodomainsDiscovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains
Structural highlights
Disease[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.[1] [2] Function[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMedThe bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure-activity relationship (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3 and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers. Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains.,Mirguet O, Gosmini R, Toum J, Clement CA, Barnathan M, Brusq JM, Mordaunt JE, Grimes R, Crowe M, Pineau O, Ajakane M, Daugan A, Jeffrey P, Cutler L, Haynes A, Smithers N, Chung CW, Bamborough P, Uings IJ, Lewis T, Witherington J, Parr N, Prinjha R, Nicodeme E J Med Chem. 2013 Sep 9. PMID:24015967[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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