Recent Developments in Targeting Bromodomain and Extra Terminal Domain Proteins for Cancer Therapeutics

Curr Med Chem. 2022;29(25):4391-4409. doi: 10.2174/0929867329666220211091806.

Abstract

Bromodomain and extra-terminal domain (BET) proteins are a well-studied family of proteins associated with a variety of diseases, including malignancy and chronic inflammation. Currently, numerous pan BET inhibitors have exhibited potent efficacy in several in vivo preclinical models and entered clinical trials but have largely stalled due to their adverse events. Therefore, the development of new selective inhibitors and PROTACs (Proteolysis Targeting Chimeras) targeting BET is urgently needed. In the present review, we summarize the BET protein structure and the recent development in BET inhibitors, focusing mainly on BRD4-selective inhibitors and PROTAC degraders.

Keywords: BET; BRD4; Cancer; PROTAC; drug design; inhibitor.

Publication types

  • Review

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Nuclear Proteins* / metabolism
  • Protein Domains
  • Proteolysis
  • Transcription Factors / metabolism

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • Nuclear Proteins
  • Transcription Factors