Current strategies for improving limitations of proteolysis targeting chimeras

作     者：Chunlan Pu Shirui Wang Lei Liu Zhonghui Feng Hongjia Zhang Qianyuan Gong Yueshan Sun Yuanbiao Guo Rui Li Chunlan Pu;Shirui Wang;Lei Liu;Zhonghui Feng;Hongjia Zhang;Qianyuan Gong;Yueshan Sun;Yuanbiao Guo;Rui Li

作者机构：Medical Research CenterThe Third People’s Hospital of ChengduThe Affiliated Hospital of Southwest Jiaotong UniversityThe Second Chengdu Hospital Affiliated to Chongqing Medical UniversityChengdu 610031China State Key Laboratory of BiotherapyCollaborative Innovation Center of Biotherapy and Cancer CenterWest China Hospital of Sichuan UniversityChengdu 610041China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2023年第34卷第6期

页      面：144-156页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

基　　金：supported by National Natural Science Foundation of China(No.81773195) Sichuan Science and Technology Program(No.2021YJ0220) Technology Innovation Research and Development Project of Chengdu(No.2022-YF05-01982-SN) the Foundation of Science and Technology Department of Sichuan Province(No.2022YFS0172) 

主　　题：PROTACs Targeted protein degradation Oral bioavailability Cell permeability Tumor targeting 

摘      要：Proteolysis targeting chimeras(PROTACs)are bifunctional degrader molecules via hijacking the ubiquitinproteasome system(UPS)to specifically eliminate targeted *** have gained momentum as a new modality of attractive technologies in the drug discovery landscape,since it allows to degrade disease-related proteins *** some PROTACs drugs reached the clinical research,they are still facing some bottlenecks and challenges that should not be neglected,such as poor oral bioavailability and potential toxic side *** overcome these limitations,herein,we provide an overview of recent strategies for improving the durability of PROTACs by enhancing cell permeability and reducing toxic side ***,the impact of these strategies on improving oral bioavailability as well as their advantages and drawbacks will also be *** review will give a useful reference toolbox for PROTACs design and further promote its clinical application.