| Literature DB >> 26771107 |
Susan M Westaway1, Alex G S Preston1, Michael D Barker1, Fiona Brown2, Jack A Brown1, Matthew Campbell1, Chun-Wa Chung2, Hawa Diallo1, Clement Douault1, Gerard Drewes3, Robert Eagle2, Laurie Gordon2, Carl Haslam2, Thomas G Hayhow1, Philip G Humphreys1, Gerard Joberty3, Roy Katso2, Laurens Kruidenier1, Melanie Leveridge2, John Liddle1, Julie Mosley2, Marcel Muelbaier3, Rebecca Randle2, Inma Rioja1, Anne Rueger3, Gail A Seal1, Robert J Sheppard1, Onkar Singh2, Joanna Taylor2, Pamela Thomas2, Douglas Thomson3, David M Wilson1, Kevin Lee1, Rab K Prinjha1.
Abstract
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).Entities:
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Year: 2016 PMID： 26771107 DOI： 10.1021/acs.jmedchem.5b01537
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446