Introduction: Bromodomain and extraterminal (BET) proteins are epigenetic readers that regulate gene transcription and cell growth by binding to acetylated lysine residues on histones. They are involved in many physiological processes and pathological conditions, such as cancer, inflammation, and metabolic diseases. Blockade of BET proteins has become an encouraging approach for the treatment of these human diseases, especially cancer. To date, a number of potent and specific BET inhibitors have been discovered and many of them have entered clinical trials.
Areas covered: This review aims at providing an overview of molecular mechanisms of BET inhibitors and highlighting the research advancements published in recent patent literatures between 2018 and 2021. Web of Science, PubMed, SciFinder, WIPO, EPO, USPTO and CNIPA databases were used for searching the literature and patents for BET inhibitors.
Expert opinion: In recent years, an increasing number of structurally diverse BET inhibitors have been identified, including pan BET inhibitors, BD1 or BD2 selective BET inhibitors, bivalent BET inhibitors, kinase and BET dual inhibitors, and BET-PROTACs. Despite many challenges, BET inhibitors have high potential in the treatment of cancer and other diseases, and the development of next-generation BET inhibitors could be promising.
Keywords: BET inhibitor; cancer therapy; patent; small molecule.