| Autor: |
Laurens Kruidenier, Rebecca Randle, Hawa Diallo, Inma Rioja, Clement Douault, Anne Rueger, Chun-wa Chung, Thomas George Christopher Hayhow, Rab K. Prinjha, Alex Preston, Roy Katso, Matthew Campbell, Michael David Barker, J. Mosley, Kevin Lee, Joanna Taylor, Marcel Muelbaier, Douglas W. Thomson, Gail A. Seal, Jack A. Brown, Susan Marie Westaway, Onkar M. P. Singh, Gerard Joberty, Philip G. Humphreys, Melanie Leveridge, Laurie J. Gordon, Pamela Thomas, Carl Haslam, Fiona Brown, John Liddle, Gerard Drewes, Robert Eagle, Robert J. Sheppard, David Matthew Wilson |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Journal of medicinal chemistry. 59(4) |
| ISSN: |
1520-4804 |
| Popis: |
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). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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