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Advances in selective inhibitors targeting the BD1 and BD2 domains of BET proteins

Jia-Yao Xie1, Ye-Wei Pang1, Cheng-Lin Yu1

  • 1Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, China.

European Journal of Medicinal Chemistry
|July 2, 2026
PubMed

Insights

Selective bromodomain and extra-terminal (BET) inhibitors offer a promising therapeutic strategy. Targeting specific bromodomains (BD1 or BD2) may overcome the adverse effects of current pan-BET inhibitors for treating various diseases.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Drug Discovery

Background:

  • Bromodomain and extra-terminal (BET) proteins are crucial epigenetic regulators.
  • Aberrant BET protein expression leads to gene dysregulation, contributing to inflammation, cancer, and neurological disorders.

Purpose of the Study:

  • To review the structure and function of BET proteins.
  • To summarize advances in developing domain-selective BET inhibitors (targeting BD1 or BD2).
  • To guide the rational design of next-generation, highly selective therapeutics.

Main Methods:

  • Literature review of BET protein function.
  • Analysis of recent developments in domain-selective BET inhibitor discovery.

Main Results:

  • Pan-BET inhibitors face challenges due to lack of selectivity and associated toxicities.
  • Development of selective inhibitors targeting individual bromodomains (BD1 or BD2) is a key research focus.

Conclusions:

  • Domain-selective BET inhibitors hold potential for improved therapeutic outcomes.
  • Further understanding of BET protein mechanisms is crucial for designing safer and more effective drugs.
Keywords:
BD1 selectivityBD2 selectivityBETEpigenetic therapySmall molecule inhibitors

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