首页|Expanding the horizons of targeted protein degradation:A non-small molecule perspective

Expanding the horizons of targeted protein degradation:A non-small molecule perspective

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Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation.Non-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms.Herein we summa-rize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.

Targeted protein degradationProteolysis targeting chimeraEndocytosisAutophagyProximity-inducing modalityPost-translational modification

Xiaowei Huang、Fengbo Wu、Jing Ye、Lian Wang、Xiaoyun Wang、Xiang Li、Gu He

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Department of Pharmacy and Department of Dermatology & Venerology,West China Hospital,Sichuan University,Chengdu 610041,China

Laboratory of Dermatology,Clinical Institute of Inflammation and Immunology,Frontiers Science Center for Disease-Related Molecular Network and State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China

Department of Urology,West China Hospital,Sichuan University,Chengdu 610041,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaChina Postdoctoral Science FoundationPostDoctor Research Project,West China Hospital,Sichuan University,ChinaSichuan Natural Science Foundation Project,China1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,China

221770848227355982103757820734732022M7222832023HXBH0762023NSFSC1554ZYJC21036

2024

10.1016/j.apsb.2024.01.010

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(6)
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