Cytotoxic activity of bromodomain inhibitor NVS-CECR2-1 on human cancer cells

Bromodomain (BRD), a protein module that recognizes acetylated lysine residues on histones and other proteins, has recently emerged as a promising therapeutic target for human diseases such as Cancer. While most of the studies have been focused on inhibitors against BRDs of the bromo- and extra-terminal domain (BET) family proteins, non-BET family BRD inhibitors remain largely unexplored. Here, we investigated a potential Anticancer activity of the recently developed non-BET family Brd Inhibitor NVS-CECR2-1 that targets the cat eye syndrome chromosome region, candidate 2 (CECR2). We show that NVS-CECR2-1 inhibits chromatin binding of CECR2 BRD and displaces CECR2 from chromatin within cells. NVS-CECR2-1 exhibits cytotoxic activity against various human Cancer cells, killing SW48 colon Cancer cells in particular with a submicromolar half maximum inhibition value mainly by inducing Apoptosis. The sensitivity of the Cancer cells to NVS-CECR2-1 is reduced by CECR2 depletion, suggesting that NVS-CECR2-1 exerts its activity by targeting CECR2. Interestingly, our data show that NVS-CECR2-1 also kills Cancer cells by CECR2-independent mechanism. This study reports for the first time the Cancer cell cytotoxic activity for NVS-CECR2-1 and provides a possibility of this Brd Inhibitor to be developed as an Anticancer therapeutic agent.