7oe4: Difference between revisions
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==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-methyl-4-propionyl-1H-pyrrole-2-carboxamide== | ==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N-methyl-4-propionyl-1H-pyrrole-2-carboxamide== | ||
<StructureSection load='7oe4' size='340' side='right'caption='[[7oe4]]' scene=''> | <StructureSection load='7oe4' size='340' side='right'caption='[[7oe4]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OE4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7oe4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OE4 FirstGlance]. <br> | ||
</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=7oe4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oe4 OCA], [https://pdbe.org/7oe4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oe4 RCSB], [https://www.ebi.ac.uk/pdbsum/7oe4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oe4 ProSAT]</span></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=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=V9B:N-methyl-4-propanoyl-1H-pyrrole-2-carboxamide'>V9B</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7oe4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oe4 OCA], [https://pdbe.org/7oe4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oe4 RCSB], [https://www.ebi.ac.uk/pdbsum/7oe4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oe4 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN]] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The profound efficacy of pan-BET inhibitors is well documented, but these epigenetic agents have shown pharmacology-driven toxicity in oncology clinical trials. The opportunity to identify inhibitors with an improved safety profile by selective targeting of a subset of the eight bromodomains of the BET family has triggered extensive medicinal chemistry efforts. In this article, we disclose the identification of potent and selective drug-like pan-BD2 inhibitors such as pyrazole 23 (GSK809) and furan 24 (GSK743) that were derived from the pyrrole fragment 6. We transpose the key learnings from a previous pyridone series (GSK620 2 as a representative example) to this novel class of inhibitors, which are characterized by significantly improved solubility relative to our previous research. | |||
Fragment-based Scaffold Hopping: Identification of Potent, Selective, and Highly Soluble Bromo and Extra Terminal Domain (BET) Second Bromodomain (BD2) Inhibitors.,Seal JT, Atkinson SJ, Bamborough P, Bassil A, Chung CW, Foley J, Gordon L, Grandi P, Gray JRJ, Harrison LA, Kruger RG, Matteo JJ, McCabe MT, Messenger C, Mitchell D, Phillipou A, Preston A, Prinjha RK, Rianjongdee F, Rioja I, Taylor S, Wall ID, Watson RJ, Woolven JM, Wyce A, Zhang XP, Demont EH J Med Chem. 2021 Jul 13. doi: 10.1021/acs.jmedchem.1c00365. PMID:34255512<ref>PMID:34255512</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7oe4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chung C]] | [[Category: Chung, C]] | ||
[[Category: Bromodomain]] | |||
[[Category: Inhibitor]] | |||
[[Category: Nuclear protein]] | |||