Development of small molecule extracellular signal-regulated kinases(ERKs) inhibitors for cancer therapy  

作　　者：Xiaoli Pan Junping Pei Aoxue Wang Wen Shuai Lu Feng Faqian Bu Yumeng Zhu Lan Zhang Guan Wang Liang Ouyang 

机构地区：[1]State Key Laboratory of Biotherapy and Cancer Center,Innovation Center of Nursing Research,Nursing Key Laboratory of Sichuan Province,National Clinical Research Center for Geriatrics,West China Hospital,and Collaborative Innovation Center of Biotherapy,Sichuan University,Chengdu 610041,China [2]Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs,School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第5期2171-2192,共22页药学学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (Grants 22177083,81922064,81874290,and 81803755);Sichuan Science and Technology Program (Grant No.2020JDRC0053,China);Fundamental Research Funds for the Central Universities (Grant No.2682020CX56,China);National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University (Grant Z20201004,China)。

摘　　要：The mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase 1/2(ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance.

关 键 词：Mitogen-activated protein kinases Cancer Extracellular signalregulated kinase 1/2 inhibitors Extracellular signalregulated kinase 5 inhibitors INHIBITION SELECTIVITY 

分 类 号：R730.5[医药卫生—肿瘤]