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

Authors
  • Yang, Yifei1
  • Wu, Zhenwei2
  • Chen, Pan1
  • Zheng, Peiyuan2
  • Zhang, Huibin2
  • Zhou, Jinpei1
  • 1 Department of Medicinal Chemistry, China Pharmaceutical University, Tongjia Xiang 24, Nanjing, 210009, PR China. , (China)
  • 2 Center of Drug Discovery, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing, 210009, PR China. , (China)
Type
Published Article
Journal
Future Medicinal Chemistry
Publisher
"Future Science, LTD"
Publication Date
Sep 01, 2020
Volume
12
Issue
18
Pages
1669–1683
Identifiers
DOI: 10.4155/fmc-2017-0264
PMID: 32893690
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Bromodomain and extra-terminal domain (BET) protein family plays an important role in regulating gene transcription preferentially at super-enhancer regions and has been involved with several types of cancers as a candidate. Up to now, there are 16 pan-BET inhibitors in clinical trials, however, most of them have undesirable off-target and side-effects. The proteolysis-targeting chimeras technology through a heterobifunctional molecule to link the target protein and E3 ubiquitin ligase, causes the target's ubiquitination and subsequent degradation. By using this technology, the heterobifunctional small-molecule BET degraders can induce BET protein degradation. In this review, we discuss the advances in the drug discovery and development of BET-targeting proteolysis-targeting chimeras.

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