View source for 7nq9


==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 2-benzyl-N-cyclopropyl-6-(1-methyl-1H-1,2,3-triazol-4-yl)isonicotinamide==
<StructureSection load='7nq9' size='340' side='right'caption='[[7nq9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NQ9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.602&#8491;</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=UMB:6-benzyl-N4-((1r,3r)-3-hydroxycyclobutyl)-N2-methylpyridine-2,4-dicarboxamide'>UMB</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=7nq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nq9 OCA], [https://pdbe.org/7nq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nq9 RCSB], [https://www.ebi.ac.uk/pdbsum/7nq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nq9 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
A number of reports have recently been published describing the discovery and optimization of bromo and extraterminal inhibitors which are selective for the second bromodomain (BD2); these include our own work toward GSK046 (3) and GSK620 (5). This paper describes our approach to mitigating the genotoxicity risk of GSK046 by replacement of the acetamide functionality with a heterocyclic ring. This was followed by a template-hopping and hybridization approach, guided by structure-based drug design, to incorporate learnings from other BD2-selective series, optimize the vector for the amide region, and explore the ZA cleft, leading to the identification of potent, selective, and bioavailable compounds 28 (GSK452), 39 (GSK737), and 36 (GSK217).

Template-Hopping Approach Leads to Potent, Selective, and Highly Soluble Bromo and Extraterminal Domain (BET) Second Bromodomain (BD2) Inhibitors.,Aylott HE, Atkinson SJ, Bamborough P, Bassil A, Chung CW, Gordon L, Grandi P, Gray JRJ, Harrison LA, Hayhow TG, Messenger C, Mitchell D, Phillipou A, Preston A, Prinjha RK, Rianjongdee F, Rioja I, Seal JT, Wall ID, Watson RJ, Woolven JM, Demont EH J Med Chem. 2021 Mar 4. doi: 10.1021/acs.jmedchem.0c02156. PMID:33662213<ref>PMID:33662213</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7nq9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Chung CW]]