Identification of a Benzoisoxazoloazepine Inhibitor (CPI 0610) of the Bromodomain and Extra Terminal (BET) Family as a Candidate for Human Clinical Trials.
In recent years, inhibition of the interaction between the bromodomain and extra terminal domain (BET) family of chromatin adaptors and acetyl lysine residues on chromatin has emerged as a promising approach to regulate the expression of important disease relevant genes, including MYC, BCL 2, and NF kB. Here we describe the identification and characterization of a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor that attenuates BET dependent gene expression in vivo, demonstrates antitumor efficacy in an MV 4 11 mouse xenograft model, and is currently undergoing human clinical trials for hematological malignancies (CPI 0610)
Journal of medicinal chemistry