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ID: ALA5120801

Journal: J Med Chem

Title: Targeting Bromodomain-Selective Inhibitors of BET Proteins in Drug Discovery and Development.

Authors: Chen J, Tang P, Wang Y, Wang J, Yang C, Li Y, Yang G, Wu F, Zhang J, Ouyang L.

Abstract: Blocking the interactions between bromodomain and extraterminal (BET) proteins and acetylated lysines of histones by small molecules has important implications for the treatment of cancers and other diseases. Many pan-BET inhibitors have shown satisfactory results in clinical trials, but their potential for poor tolerability and toxicity persist. However, recently reported studies illustrate that some BET bromodomain (BET-BD1 or BET-BD2)-selective inhibitors have advantage over pan-inhibitors, including reduced toxicity concerns. Furthermore, some selective BET inhibitors have similar or even better therapeutic efficacy in inflammatory diseases or cancers. Therefore, the development of selective BET inhibitors has become a hot spot for medicinal chemists. Here, we summarize the known selective BET-BD1 and BET-BD2 inhibitors and review the methods for enhancing the selectivity and potency of these inhibitors based on their different modes of interactions with BET-BD1 or BET-BD2. Finally, we discuss prospective strategies that selectively target the bromodomains of BET proteins.

CiteXplore: 35324195

DOI: 10.1021/acs.jmedchem.1c01835