Genome-wide pan-GPCR cell libraries accelerate drug discovery  

作　　者：Hanting Yang Yongfu Wang Wei Liu Taiping He Jiayu Liao Zhongzhi Qian Jinghao Zhao Zhaotong Cong Dan Sun Zhixiang Liu Can Wang Lingping Zhu Shilin Chen 

机构地区：[1]School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [2]Institute of Herbgenomics,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [3]School of Basic Medical Science,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [4]Department of Bioengineering,University of California,Riverside,CA 92521,USA [5]The Huaxi-Cal Research Center for Predictive Intervention Medicine,West China Hospital,Sichuan University,Chengdu 610041,China [6]Chinese Pharmacopoeia Commission,Beijing 100061,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第10期4296-4311,共16页药学学报（英文版）

基　　金：supported by introducing the talented person scientific research starts funds subsidization project of Chengdu University of Traditional Chinese Medicine(030040019,030040017,China).

摘　　要：G protein-coupled receptors(GPCRs)are pivotal in mediating diverse physiological and pathological processes,rendering them promising targets for drug discovery.GPCRs account for about 40%of FDA-approved drugs,representing the most successful drug targets.However,only approximately 15%of the 800 human GPCRs are targeted by market drugs,leaving numerous opportunities for drug discovery among the remaining receptors.Cell expression systems play crucial roles in the GPCR drug discovery field,including novel target identification,structural and functional characterization,potential ligand screening,signal pathway elucidation,and drug safety evaluation.Here,we discuss the principles,applications,and limitations of widely used cell expression systems in GPCR-targeted drug discovery,GPCR function investigation,signal pathway characterization,and pharmacological property studies.We also propose three strategies for constructing genome-wide pan-GPCR cell libraries,which will provide a powerful platform for GPCR ligand screening,and facilitate the study of GPCR mechanisms and drug safety evaluation,ultimately accelerating the process of GPCR-targeted drug discovery.

关 键 词：G-protein coupled receptors Genome-wide pan-GPCR Transgenic cell library High-throughput screening Drug discovery 

分 类 号：R914[医药卫生—药物化学]