Virtual Fragment Screening Identification of a Quinoline-5,8-dicarboxylic Acid Derivative as a Selective JMJD3 Inhibitor.
Giordano A., Del Gaudio F., Johansson C., Riccio R., Oppermann U., Di Micco S.
The quinoline-5,8 dicarboxylic acid scaffold has been identified by a fragment-based approach as new potential lead compound for the development of JMJD3 inhibitors. Among them, 3-(2,4-dimethoxypyrimidin-5-yl)quinoline-5,8-dicarboxylic acid (compound 3) shows low micromolar inhibitory activity against Jumonji domain-containing protein 3 (JMJD3). The experimental evaluation of inhibitory activity against seven related isoforms of JMJD3 highlighted an unprecedented selectivity toward the biological target of interest.