View source for 7nq2


==C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH (S)-N4-cyclopropyl-N2-methyl-6-(1-phenylethyl)pyridine-2,4-dicarboxamide==
<StructureSection load='7nq2' size='340' side='right'caption='[[7nq2]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NQ2 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]] 1.735&#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=ULE:~{N}4-cyclopropyl-~{N}2-methyl-6-[(1~{S})-1-phenylethyl]pyridine-2,4-dicarboxamide'>ULE</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=7nq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nq2 OCA], [https://pdbe.org/7nq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nq2 RCSB], [https://www.ebi.ac.uk/pdbsum/7nq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nq2 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Domain-specific BET bromodomain ligands represent an attractive target for drug discovery with the potential to unlock the therapeutic benefits of antagonizing these proteins without eliciting the toxicological aspects seen with pan-BET inhibitors. While we have reported several distinct classes of BD2 selective compounds, namely, GSK620, GSK549, and GSK046, only GSK046 shows high aqueous solubility. Herein, we describe the lead optimization of a further class of highly soluble compounds based upon a picolinamide chemotype. Focusing on achieving &gt;1000-fold selectivity for BD2 over BD1 ,while retaining favorable physical chemical properties, compound 36 was identified as being 2000-fold selective for BD2 over BD1 (Brd4 data) with &gt;1 mg/mL solubility in FaSSIF media. 36 represents a valuable new in vivo ready molecule for the exploration of the BD2 phenotype.

Identification of a Series of N-Methylpyridine-2-carboxamides as Potent and Selective Inhibitors of the Second Bromodomain (BD2) of the Bromo and Extra Terminal Domain (BET) Proteins.,Harrison LA, Atkinson SJ, Bassil A, Chung CW, Grandi P, Gray JRJ, Levernier E, Lewis A, Lugo D, Messenger C, Michon AM, Mitchell DJ, Preston A, Prinjha RK, Rioja I, Seal JT, Taylor S, Wall ID, Watson RJ, Woolven JM, Demont EH J Med Chem. 2021 Jul 7. doi: 10.1021/acs.jmedchem.0c02155. PMID:34232650<ref>PMID:34232650</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7nq2" style="background-color:#fffaf0;"></div>

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