6df7: Difference between revisions
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==TAF1-BD2 in complex with Cpd27 (6-(but-3-en-1-yl)-4-(1-methyl-6-(morpholine-4-carbonyl)-1H-benzo[d]imidazol-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one)== | |||
<StructureSection load='6df7' size='340' side='right' caption='[[6df7]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6df7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DF7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DF7 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G9V:6-(but-3-en-1-yl)-4-[1-methyl-6-(morpholine-4-carbonyl)-1H-benzimidazol-4-yl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one'>G9V</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6df4|6df4]]</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=6df7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6df7 OCA], [http://pdbe.org/6df7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6df7 RCSB], [http://www.ebi.ac.uk/pdbsum/6df7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6df7 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The biological functions of the dual bromodomains of human transcription-initiation-factor TFIID subunit 1 (TAF1(1,2)) remain unknown, although TAF1 has been identified as a potential target for oncology research. Here, we describe the discovery of a potent and selective in vitro tool compound for TAF1(2), starting from a previously reported lead. A cocrystal structure of lead compound 2 bound to TAF1(2) enabled structure-based design and structure-activity-relationship studies that ultimately led to our in vitro tool compound, 27 (GNE-371). Compound 27 binds TAF1(2) with an IC50 of 10 nM while maintaining excellent selectivity over other bromodomain-family members. Compound 27 is also active in a cellular-TAF1(2) target-engagement assay (IC50 = 38 nM) and exhibits antiproliferative synergy with the BET inhibitor JQ1, suggesting engagement of endogenous TAF1 by 27 and further supporting the use of 27 in mechanistic and target-validation studies. | |||
GNE-371, a Potent and Selective Chemical Probe for the Second Bromodomains of Human Transcription-Initiation-Factor TFIID Subunit 1 and Transcription-Initiation-Factor TFIID Subunit 1-like.,Wang S, Tsui V, Crawford TD, Audia JE, Burdick DJ, Beresini MH, Cote A, Cummings R, Duplessis M, Flynn EM, Hewitt MC, Huang HR, Jayaram H, Jiang Y, Joshi S, Murray J, Nasveschuk CG, Pardo E, Poy F, Romero FA, Tang Y, Taylor AM, Wang J, Xu Z, Zawadzke LE, Zhu X, Albrecht BK, Magnuson SR, Bellon S, Cochran AG J Med Chem. 2018 Oct 25;61(20):9301-9315. doi: 10.1021/acs.jmedchem.8b01225. Epub, 2018 Oct 5. PMID:30289257<ref>PMID:30289257</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6df7" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Murray, J M]] | |||
[[Category: Bromodomain]] | |||
[[Category: Sbdd]] | |||
[[Category: Small molecule inhibitor]] | |||
[[Category: Taf1-bd2]] | |||
[[Category: Transcription-inhibitor complex]] | |||