Beyond canonical PROTAC: biological targeted protein degradation (bioTPD)

Biomaterials Research

Review

Le Yu¹  Runhua Zhou¹  Guangwei Shi¹  Liuhai Zheng²  Lingyun Dai²  Huifang Wang²  Pan Zhao²  Zhijie Li²  Jigang Wang³  Chengchao Xu⁴  Jianhong Wang⁵  Fushan Xu⁶  Kongjun Yang⁶ 

[1] School of Pharmaceutical Science, Southern Medical University, 510515, Guangzhou, P. R. China;Shenzhen Institute of Respiratory Disease, Shenzhen Clinical Research Centre for Respirology, The Second Clinical Medical College, The First Affiliated Hospital, Shenzhen People’s Hospital, Jinan University, Southern University of Science and Technology, 518020, Shenzhen, Guangdong, P. R. China;Shenzhen Institute of Respiratory Disease, Shenzhen Clinical Research Centre for Respirology, The Second Clinical Medical College, The First Affiliated Hospital, Shenzhen People’s Hospital, Jinan University, Southern University of Science and Technology, 518020, Shenzhen, Guangdong, P. R. China;School of Pharmaceutical Science, Southern Medical University, 510515, Guangzhou, P. R. China;State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, P. R. China;Shenzhen Institute of Respiratory Disease, Shenzhen Clinical Research Centre for Respirology, The Second Clinical Medical College, The First Affiliated Hospital, Shenzhen People’s Hospital, Jinan University, Southern University of Science and Technology, 518020, Shenzhen, Guangdong, P. R. China;State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, P. R. China;Shenzhen Mental Health Center, Shenzhen Kangning Hospital, 518020, Shenzhen, Guangdong, P. R. China;The Second Clinical Medical College, The First Affiliated Hospital, Shenzhen People’s Hospital, Jinan University, Southern University of Science and Technology, 518020, Shenzhen, Guangdong, P. R. China;

关键词: Biological targeted protein degradation (bioTPD);    Peptide;    Antibody;    Fusion protein;    Nucleic acid;   

DOI  :  10.1186/s40824-023-00385-8

 received in 2023-01-01, accepted in 2023-04-21,  发布年份 2023

来源: Springer

【 摘 要 】

Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential to modulate disease-associated proteins that have previously been considered undruggable, by employing the host destruction machinery. The exploration and discovery of cellular degradation pathways, including but not limited to proteasomes and lysosome pathways as well as their degraders, is an area of active research. Since the concept of proteolysis-targeting chimeras (PROTACs) was introduced in 2001, the paradigm of TPD has been greatly expanded and moved from academia to industry for clinical translation, with small-molecule TPD being particularly represented. As an indispensable part of TPD, biological TPD (bioTPD) technologies including peptide-, fusion protein-, antibody-, nucleic acid-based bioTPD and others have also emerged and undergone significant advancement in recent years, demonstrating unique and promising activities beyond those of conventional small-molecule TPD. In this review, we provide an overview of recent advances in bioTPD technologies, summarize their compositional features and potential applications, and briefly discuss their drawbacks. Moreover, we present some strategies to improve the delivery efficacy of bioTPD, addressing their challenges in further clinical development.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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