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

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.

journal_name

Future Med Chem

authors

Yang Y,Wu Z,Chen P,Zheng P,Zhang H,Zhou J

doi

10.4155/fmc-2017-0264

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

1669-1683

issue

18

eissn

1756-8919

issn

1756-8927

journal_volume

12

pub_type

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