A patent review of BRD4 inhibitors (2013-2019)

Introduction: The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal (BET) family, functions as an 'epigenetic reader' that binds to acetylated lysine (KAc) residues on histone tails sophisticatedly regulating chromatin structure and gene expression. Recently, emerging evidence demonstrates that BRD4 plays a significant role in the occurrence and progression of several malignant human diseases especially cancers, making it a hot target in cancer therapy. Areas covered: This review mainly summarizes the patents of BRD4 inhibitors that have been authorized from 2013 to 2019. The patents are mostly described in terms of chemical structures, molecular mechanisms of action, pharmacological activities and potential clinical applications, including combination therapies. The development of BRD4 inhibitors in the clinical phase has been highlighted. Prospects for further development of more selective BRD4 inhibitors are provided. Expert opinion: In 2013-2019, several previously known chemical scaffolds have been further developed and disclosed. Although many small molecule BRD4 inhibitors with high potency and diverse scaffolds have been developed, the selectivity of most BRD4 inhibitors still needs to be improved. Therefore, the development of more selective small molecule inhibitors or combined use of drugs such as immunotherapy may provide new ideas for drug development.