A comprehensive review of BET-targeting PROTACs for cancer therapy.

Xiao-Li Zhou, Fang Zhao, Yong-Tao Xu, Yuan-Yuan Guan, Tong Yu, Yi-Zhe Zhang, Ying-Chao Duan, Yuan Zhao

Journal: Bioorganic & medicinal chemistry 2022;73():117033

PMID: 36202064

Full Text on Elsevier Science View on PubMed

Abstract

Targeted protein degradation using proteolysis-targeting chimeras (PROTACs) has emerged as an effective strategy for drug discovery, given their unique advantages over target protein inhibition. The bromodomain and extra-terminal (BET) family proteins play a key role in regulating oncogene expression and are considered attractive therapeutic targets for cancer therapy. Considering the therapeutic potential of BET proteins in cancer and the marked attractiveness of PROTACs, BET-targeting PROTACs have been extensively pursued. Recently, BET-targeting PROTACs based on new E3 ligases and novel strategies, such as light-activated, macrocyclic, folate-caged, aptamer-PROTAC conjugation, antibody-coupling, and autophagy-targeting strategies, have emerged. In the present review, we provide a comprehensive summary of advances in BET-targeting PROTACs.

Address: Sanquan college of Xinxiang Medical University, 453003 Xinxiang, Henan Province, PR China.; School of Medical Engineering, Xinxiang Medical University, 453003 Xinxiang, Henan Province, PR China.; School of Pharmacy, Xinxiang Medical University, 453003 Xinxiang, Henan Province, PR China.; School of Pharmacy, Xinxiang Medical University, 453003 Xinxiang, Henan Province, PR China. Electronic address: [email protected].; Sanquan college of Xinxiang Medical University, 453003 Xinxiang, Henan Province, PR China. Electronic address: [email protected].

DOI: 10.1016/j.bmc.2022.117033