Advances in Research on Selective BRD4 BD1/BRD4 BD2 Inhibitors

Bromodomain-containing protein 4 (BRD4), which plays an important role in the process of histone acetylation modification, is closely related to the occurrence and development of a variety of diseases including cancer. Currently, plenty of BRD4 inhibitors have entered clinical studies. The side-effects caused by poor selectivity of pan-BRD4 small molecule inhibitors have led to the termination of most clinical trials. Highly selective inhibitors of BRD4 targeting cancer have become a new trend in the development of BRD4 inhibitors. This article introduces the structure and biological function of BRD4 protein, reviews the selective BRD4 BD1/BRD4 BD2 inhibitors previously reported, and summarizes the structural basis and unique indications for the selectivity of BRD4 selective inhibitors, aiming to deepen the understanding of BRD4 protein function and lay the foundation for the subsequent design and expansion of highly selective BRD4 inhibitors.