AI Article Synopsis
- Optimization of KDM6B HTS hit 12 led to the discovery of two new compounds, 34 and 39, as KDM4 family histone lysine demethylase inhibitors.
- These compounds show strong activity with IC50 values ≤ 100 nM in biochemical assays and demonstrate high selectivity against KDM6B.
- Additionally, compounds 34 and 39 are effective at inhibiting KDM5C with IC50 values in the range of 100-125 nM.
Article 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).
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| http://dx.doi.org/10.1021/acs.jmedchem.5b01537 | DOI Listing |
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