1461603-00-8Relevant articles and documents
Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives
Westaway, Susan M.,Preston, Alex G.S.,Barker, Michael D.,Brown, Fiona,Brown, Jack A.,Campbell, Matthew,Chung, Chun-Wa,Diallo, Hawa,Douault, Clement,Drewes, Gerard,Eagle, Robert,Gordon, Laurie,Haslam, Carl,Hayhow, Thomas G.,Humphreys, Philip G.,Joberty, Gerard,Katso, Roy,Kruidenier, Laurens,Leveridge, Melanie,Liddle, John,Mosley, Julie,Muelbaier, Marcel,Randle, Rebecca,Rioja, Inma,Rueger, Anne,Seal, Gail A.,Sheppard, Robert J.,Singh, Onkar,Taylor, Joanna,Thomas, Pamela,Thomson, Douglas,Wilson, David M.,Lee, Kevin,Prinjha, Rab K.
, p. 1357 - 1369 (2016/03/05)
Optimization 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 μM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM).
