Discovery and anti-tumor activity of 4-(benzylamino)-6-(3,5-dimethylisoxazol-4-yl)quinolin-2(1H)-one (CG13250), a potent, selective and orally bioavailable BET bromodomain inhibitor.

The bromodomain and extra-terminal domain (BET) proteins are epigenetic readers involved in the regulation of gene transcription. Inhibitors of the BET proteins, in particular BRD4, have demonstrated anti-tumour activities and efficacies in clinical trials. Herein, we describe the discovery of potent and selective inhibitors of BRD4, and demonstrate that the lead compound CG13250 is orally bioavailable and efficacious in a mouse xenograft model of leukemia.