Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications

作者全名："Li, Qiong; Zhou, Li; Qin, Siyuan; Huang, Zhao; Li, Bowen; Liu, Ruolan; Yang, Mei; Nice, Edouard C.; Zhu, Huili; Huang, Canhua"

作者地址："[Li, Qiong; Qin, Siyuan; Huang, Zhao; Li, Bowen; Yang, Mei; Huang, Canhua] Sichuan Univ, State Key Lab Biotherapy, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China; [Li, Qiong; Qin, Siyuan; Huang, Zhao; Li, Bowen; Yang, Mei; Huang, Canhua] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China; [Li, Qiong; Qin, Siyuan; Huang, Zhao; Li, Bowen; Yang, Mei; Huang, Canhua] Sichuan Univ, West China Hosp, Chengdu 610041, Peoples R China; [Li, Qiong; Qin, Siyuan; Huang, Zhao; Li, Bowen; Yang, Mei; Huang, Canhua] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China; [Zhou, Li] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis,Minist, Chongqing 400016, Peoples R China; [Liu, Ruolan] Chengdu Univ Tradit Chinese Med, Sch Basic Med Sci, Chengdu 611137, Peoples R China; [Nice, Edouard C.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia; [Zhu, Huili] Sichuan Univ, Dept Reprod Med, Key Lab Birth Defects & Related Dis Women & Childr, Minist Educ,West China Second Univ Hosp, Chengdu 610041, Peoples R China"

通信作者："Huang, CH (通讯作者)，Sichuan Univ, State Key Lab Biotherapy, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China.; Huang, CH (通讯作者)，Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China.; Huang, CH (通讯作者)，Sichuan Univ, West China Hosp, Chengdu 610041, Peoples R China.; Huang, CH (通讯作者)，Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China.; Zhu, HL (通讯作者)，Sichuan Univ, Dept Reprod Med, Key Lab Birth Defects & Related Dis Women & Childr, Minist Educ,West China Second Univ Hosp, Chengdu 610041, Peoples R China."

来源：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

ESI学科分类：CHEMISTRY

WOS号：WOS:001013083000001

JCR分区：Q1

影响因子：6

年份：2023

卷号：257

期号：　

开始页：　

结束页：　

文献类型：Review

关键词：PROTACs; Biotherapeutics; Protein degradation; Drug development

摘要："The success of inhibitor-based therapeutics is largely constrained by the acquisition of therapeutic resistance, which is partially driven by the undruggable proteome. The emergence of proteolysis targeting chimera (PRO-TAC) technology, designed for degrading proteins involved in specific biological processes, might provide a novel framework for solving the above constraint. A heterobifunctional PROTAC molecule could structurally connect an E3 ubiquitin ligase ligand with a protein of interest (POI)-binding ligand by chemical linkers. Such technology would result in the degradation of the targeted protein via the ubiquitin-proteasome system (UPS), opening up a novel way of selectively inhibiting undruggable proteins. Herein, we will highlight the advantages of PROTAC technology and summarize the current understanding of the potential mechanisms involved in biotherapeutics, with a particular focus on its application and development where therapeutic benefits over classical small -molecule inhibitors have been achieved. Finally, we discuss how this technology can contribute to developing biotherapeutic drugs, such as antivirals against infectious diseases, for use in clinical practices."

基金机构："National Key Research and Development Project of China, China [2020YFA0509400]; Guangdong Basic and Applied Basic Research Foundation, China [2019B030302012]; National Natural Science Foundation of China, China [81821002, 82130082, 81790251, 81601258]; West China Hospital, Sichuan University, China [ZYGD22007]; Chengdu Science and Technology Program, China [2021-YF05-01612-SN]"

基金资助正文："This work was supported by National Key Research and Development Project of China, China (2020YFA0509400), Guangdong Basic and Applied Basic Research Foundation, China (2019B030302012), National Natural Science Foundation of China, China (81821002, 82130082, 81790251, and 81601258), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University, China (ZYGD22007), the Chengdu Science and Technology Program, China (2021-YF05-01612-SN)."