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Targeting GRK2 and GRK5 for treating chronic degenerative diseases: Advances and future perspectives

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资源类型：
Pubmed体系：
作者：
Zhang Ya[1,2,4] * ; Zhang Jifa[1,4,5] * ; Wang Jiaxing[3] ; Chen Hao[3] ; Ouyang Liang[1,4,5,*1] ; Wang Yuxi[1,4,5,*1] ;
机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]College of Life Sciences, Sichuan University, Chengdu, 610064, Sichuan, China [3]Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, 38163, Tennessee, United States [4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
出处：
DOI： 10.1016/j.ejmech.2022.114668
ISSN：

关键词： GRK2 GRK5 Structure-activity relationship Dual-target inhibitors Chronic degenerative diseases

摘要：
The development of small-molecule inhibitors targeting G protein-coupled receptor kinase 2 (GRK2) and G protein-coupled receptor kinase 5 (GRK5) for the treatment of chronic degenerative diseases has attracted wide attention. GRK2 and GRK5 can regulate essential physiological processes by phosphorylating G protein-coupled receptor (GPCR). Alterations in the functional levels of GRK2 and GRK5 have been found in a variety of chronic degenerative diseases, such as cardiovascular diseases, neurodegenerative diseases, cancers, type 2 diabetes, and rheumatoid arthritis (RA). Abnormal GRK2 and GRK5 expression contribute to the development of chronic degenerative diseases through environmental molecular mechanisms, making them promising molecular targets for treating chronic degenerative diseases. To date, many novel GRK2 and GRK5 inhibitors have been reported for the treatment of chronic degenerative diseases. We focus on the recent progress of single and dual-target inhibitors of GRK2/GRK5. This review summarizes the structural optimization rationale, structure-activity relationships (SARs), and the latest application in the treatment of chronic degenerative diseases. We believe it will shed light on the future development of small molecule inhibitors of GRK2 and GRK5, as well as the clinical applications in chronic degenerative diseases.Copyright © 2022. Published by Elsevier Masson SAS.

基金：
Sichuan Science and Technology Program (2019YFS0003), National Natural Science Foundation of China (82073318, 81922064, 81903502), National Major Scientific and Technological Special Project for Significant New Drugs Development (2018ZX09201018-021), Natural Science Foundation of Sichuan Province (2022NSFSC1365).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 药物化学
最新[2023]版：
大类 | 2 区 医学
小类 | 1 区 药物化学
第一作者：
第一作者机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]College of Life Sciences, Sichuan University, Chengdu, 610064, Sichuan, China [4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
共同第一作者：
通讯作者：
通讯机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [*1]Targeted Tracer Research and development laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, Joint Research Institution of Altitude Health, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
推荐引用方式(GB/T 7714)：
Zhang Ya,Zhang Jifa,Wang Jiaxing,et al.Targeting GRK2 and GRK5 for treating chronic degenerative diseases: Advances and future perspectives[J].European journal of medicinal chemistry.2022,243:114668.doi:10.1016/j.ejmech.2022.114668.
APA：
Zhang Ya,Zhang Jifa,Wang Jiaxing,Chen Hao,Ouyang Liang&Wang Yuxi.(2022).Targeting GRK2 and GRK5 for treating chronic degenerative diseases: Advances and future perspectives.European journal of medicinal chemistry,243,
MLA：
Zhang Ya,et al."Targeting GRK2 and GRK5 for treating chronic degenerative diseases: Advances and future perspectives".European journal of medicinal chemistry 243.(2022):114668

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