摘要
Janus激酶(Janus kinases, JAKs)属于细胞因子受体相关的酪氨酸激酶家族,其介导的信号通路被不同细胞因子激活,在人体的生理活动中扮演着重要角色。该通路中蛋白的失活、突变以及过度表达会导致严重的疾病,包括自身免疫性疾病、肿瘤和血液疾病。因此,开发以JAKs为靶点的抑制剂,对于治疗上述疾病有着非常重要的临床意义。概述JAKs家族的结构、功能以及JAKs通路与疾病间的关系,着重介绍若干具有代表意义的JAKs抑制剂,并对其结构、靶点与适应证进行分析,为开发新型JAKs抑制剂提供思路。
The Janus kinases(JAKs)belong to the family of cytokine receptor-associated tyrosine kinases and mediate signaling pathway that can be activated by different cytokines,thus playing a critical role in the physiological activities of human body.The inactivation,mutation and overexpression of the proteins in this pathway will lead to severe symptoms including autoimmune diseases,malignant carcinoma and hematological disorders.Therefore,the development of JAKs-targeted inhibitors is of a great clinical significance for the treatment of these diseases.This paper briefly discussed the structure/function of the JAKs family and the relationship between JAKs signaling pathway and diseases,introduced representative JAKs inhibitors in detail and analyzed the structures,targets and indications of these inhibitors,providing new ideas for the development of novel JAKs inhibitors.
作者
黄昊哲
张吉星
刘佳
徐云根
孙丽萍
HUANG Haozhe;ZHANG Jixing;LIU Jia;XU Yungen;SUN Liping(Department of Medicinal Chemistry,School of Pharmacy,Jiangsu Key Laboratory of Drug Design&Optimization,China Pharmaceutical University,Nanjing 210009,China)
出处
《药学进展》
CAS
2019年第1期42-50,共9页
Progress in Pharmaceutical Sciences
基金
国家自然科学基金资助项目(No.21472243)
江苏省大学生创新创业训练计划项目
作者简介
通讯作者:徐云根,教授,研究方向:新药设计与合成,Tel:025-83271414,E-mail:xyg64@126.com;通讯作者:孙丽萍,教授,研究方向:小分子抑制剂的研发,Tel:025-83271414,E-mail:chsunlp@cpu.edu.cn
