5fp3 | pdb_00005fp3
Cell penetrant inhibitors of the JMJD2 (KDM4) and JARID1 (KDM5) families of histone lysine demethylases
Structural highlights
FunctionKDM6B_HUMAN Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation.[1] [2] Publication Abstract from PubMedOptimization of KDM6B (JMJD3) HTS hit 12 led to the identification of 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic acid 39 that are inhibitors of the KDM4 (JMJD2) family of histone lysine demethylases. Compounds 34 and 39 possess activity, IC50 </= 100 nM, in KDM4 family biochemical (RFMS) assays with >/=50-fold selectivity against KDM6B and activity in a mechanistic KDM4C cell imaging assay (IC50 = 6-8 muM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM). Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives.,Westaway SM, Preston AG, Barker MD, Brown F, Brown JA, Campbell M, Chung CW, Diallo H, Douault C, Drewes G, Eagle R, Gordon L, Haslam C, Hayhow TG, Humphreys PG, Joberty G, Katso R, Kruidenier L, Leveridge M, Liddle J, Mosley J, Muelbaier M, Randle R, Rioja I, Rueger A, Seal GA, Sheppard RJ, Singh O, Taylor J, Thomas P, Thomson D, Wilson DM, Lee K, Prinjha RK J Med Chem. 2016 Jan 15. PMID:26771107[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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