ROCK inhibitor:Focus on recent updates  

作　　者：Yaodong You Kun Zhu Jie Wang Qi Liang Wen Li Lin Wang Baojun Guo Jing Zhou Xuanlin Feng Jianyou Shi 

机构地区：[1]Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China [2]TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province,Chengdu 610072,China [3]Guizhou University of Traditional Chinese Medicine,Guiyang 550002,China [4]College of Medicine,Southwest Jjiaotong Unive,Chengdu 610031,China [5]College of Food and Bioengineering,Xihua University,Chengdu 610039,China [6]Department of Emergency Intensive Care Unit,Sichuan Academy of Medical Sciences&Sichuan Province People's Hospital,Chengdu 610072,China [7]Department of Pharmacy,Personalized Drug Therapy Key Laboratory of Sichuan Province,Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital,School of Medicine,University of Electronic Science and Technology,Chengdu 610072,China

出　　处：《Chinese Chemical Letters》2023年第12期111-125,共15页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.82073311 and 81973866);Natural Science Foundation of Sichuan Province(No.2022JDTD0025);Science and Technology Research Project of Sichuan Traditional Chinese Medicine Administration(No.2021ZD016).

摘　　要：Rho-associated coiled-coil-containing protein kinase(RoCK)belongs to the serine-threonine family,and RoCK is involved in a variety of biological processes including cell migration,adhesion,proliferation and differentiation through phosphorylation of different downstream substrates.The aberrant activation of ROCK is associated with the pathological conditions in different systems including various diseases,including cancer,neurological diseases,inflammation,cardiovascular diseases and glaucoma.Therefore,the ROCK inhibitors have potential applicability for treating the aforementioned diseases.Four small molecule ROCK inhibitors have been approved for clinical use:fasudil,ripasudil,netarsudil and belumosudil.In recent years,more small molecule ROCK inhibitors have been identified.This paper reviews the ROCK inhibitors reported in past seven years.We mainly focused on the summarization of the structure-activity relationships,inhibitory efficacy,pharmacological mechanisms and the relevant clinical studies of the reported ROCK inhibitors.Besides the small molecular inhibitors,the peptides and biological extracts which exhibit ROCK inhibitory effects are also included.We also provide suggestions for the future development of the potent ROCK inhibitors.

关 键 词：ROCK-I ROCK-I ROCK inhibitor ROCK signaling pathway Structure-activity relationship Pharmacological activity 

分 类 号：TQ460.1[化学工程—制药化工]