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.
Bioorg Med Chem. 2022 Nov 1;73:117033. doi: 10.1016/j.bmc.2022.117033. Epub 2022 Sep 29.
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.
靶向蛋白降解技术利用蛋白水解靶向嵌合体（PROTACs），因其具有优于靶蛋白抑制的独特优势，已成为药物发现的有效策略。溴结构域和末端（BET）家族蛋白在调节致癌基因表达方面发挥着关键作用，被认为是癌症治疗有吸引力的治疗靶点。鉴于 BET 蛋白在癌症中的治疗潜力和 PROTACs 的显著吸引力，BET 靶向 PROTACs 已被广泛研究。最近，出现了基于新型 E3 连接酶和新型策略的 BET 靶向 PROTACs，如光激活、大环、叶酸笼、适体-PROTAC 偶联、抗体偶联和自噬靶向策略。在本综述中，我们全面总结了 BET 靶向 PROTACs 的进展。
