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Proteolysis-targeting chimeras mediate the degradation of bromodomain and extra-terminal domain proteins

Yifei Yang1, Zhenwei Wu2, Pan Chen1

  • 1Department of Medicinal Chemistry, China Pharmaceutical University, Tongjia Xiang 24, Nanjing, 210009, PR China.

Future Medicinal Chemistry
|September 7, 2020
PubMed

Insights

Proteolysis-targeting chimeras offer a novel approach to degrade Bromodomain and extra-terminal domain (BET) proteins, addressing limitations of current inhibitors. This technology promises targeted cancer therapy with potentially fewer side effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Bromodomain and extra-terminal domain (BET) proteins regulate gene transcription and are implicated in various cancers.
  • Current pan-BET inhibitors in clinical trials exhibit off-target effects and undesirable side effects.
  • Proteolysis-targeting chimeras (PROTACs) offer a new therapeutic strategy by inducing target protein degradation.

Purpose of the Study:

  • To review advances in the development of BET-targeting proteolysis-targeting chimeras.
  • To highlight the potential of PROTAC technology for cancer treatment.
  • To discuss the advantages of BET degraders over traditional inhibitors.

Main Methods:

  • Review of current literature on BET protein family.
  • Analysis of proteolysis-targeting chimeras technology and its application to BET proteins.
  • Discussion of drug discovery and development strategies for BET degraders.

Main Results:

  • BET protein family is a promising target for cancer therapy.
  • Proteolysis-targeting chimeras technology enables targeted degradation of BET proteins.
  • Heterobifunctional small molecules can induce BET protein ubiquitination and degradation.

Conclusions:

  • BET-targeting proteolysis-targeting chimeras represent a significant advancement in cancer drug discovery.
  • This technology offers a potential solution to the limitations of existing BET inhibitors.
  • Further development of BET degraders holds promise for more effective and safer cancer therapies.
Keywords:
BETPROTACsdegrader

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