7nq0

C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH oxabicyclo(hexan-6-yl)-N2-methyl-6-((S)-1-phenylethyl)pyridine-2,4-dicarboxamide

spinqualitylabelsall models 7nq0, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.3Å Ligands: EDO, PE4, ULN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 >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 >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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bromodomain-containing protein 3D structures

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