Inhibitors of bromodomain and extra-terminal proteins for treating multiple human diseases

Clinical development of bromodomain and extra-terminal (BET) protein inhibitors differs from the traditional course of drug development. These drugs are simultaneously being evaluated for treating a wide spectrum of human diseases due to their novel mechanism of action. BET proteins are epigenetic readers, which play a primary role in transcription. Here, we briefly describe the BET family of proteins, of which BRD4 has been studied most extensively. We discuss BRD4 activity at latent enhancers as an example of BET protein function. We examine BRD4 redistribution and enhancer reprogramming in embryonic development, cancer, cardiovascular, autoimmune, and metabolic diseases, presenting hallmark studies that highlight BET proteins as attractive targets for therapeutic intervention. We review the currently available approaches to targeting BET proteins, methods of selectively targeting individual bromodomains, and review studies that compare the effects of selective BET inhibition to those of pan-BET inhibition. Lastly, we examine the current clinical landscape of BET inhibitor development.

Automated summary

The clinical development of BET protein inhibitors is unique, as they are being widely evaluated for treating various human diseases due to their novel mechanism of action. Among the BET protein family, BRD4 is extensively studied, and its activity at latent enhancers is a representative example of BET protein function. The role of BET proteins in embryonic development, cancer, cardiovascular, autoimmune, and metabolic diseases makes them attractive targets for therapeutic intervention.