Therapeutics: Bromodomain containing 4 (BRD4)

Rodent studies suggest BRD4 inhibitors could help treat cocaine addiction. Nucleus accumbens levels of BRD4 were higher in mouse and rat models of cocaine addiction than in normal mice and rats. In a mouse model of cocaine addiction, a tool compound that inhibits BET bromodomain proteins decreased cocaine-seeking behavior compared with vehicle, without adversely affecting learning or locomotor activity. In a rat model of cocaine addiction, injection of the BRD4 inhibitor into the nucleus accumbens decreased cocaine-seeking behavior compared with vehicle. Next steps could include investigating the role of BRD4 in other addiction models.

Resverlogix Corp. and Shenzhen Hepalink Pharmaceutical Co. Ltd. have apabetalone (RVX-208), an inhibitor of BRD4 and other BET bromodomain proteins, in Phase III testing to treat diabetes and cardiovascular disease, Phase II testing to treat atherosclerosis and Phase I testing to treat Alzheimer's disease (AD). ...