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.
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)。
作者简介
Corresponding authors:Lan Zhang.Tel./fax:+862885503817.E-mail addresses:zhanglanx_9@126.com;Corresponding authors:Guan Wang.Tel./fax:+862885503817.E-mail addresses:guan8079@163.com;Corresponding authors:Liang Ouyang.Tel./fax:+862885503817.E-mail addresses:ouyangliang@scu.edu.cn;Xiaoli Pan,These authors made equal contributions to this work;Junping Pei,These authors made equal contributions to this work;Aoxue Wang,These authors made equal contributions to this work。
