药学学报, 2016, 51(10): 1520-1529
引用本文:
殷缘, 张天泰, 张大永. JAK-3激酶及其抑制剂的研究进展[J]. 药学学报, 2016, 51(10): 1520-1529.
YIN Yuan, ZHANG Tian-tai, ZHANG Da-yong. Research progress of JAK-3 kinase and its inhibitors[J]. Acta Pharmaceutica Sinica, 2016, 51(10): 1520-1529.

JAK-3激酶及其抑制剂的研究进展
殷缘1, 张天泰2, 张大永1
1. 中国药科大学药物科学研究院, 江苏 南京 210009;
2. 中国医学科学院、北京协和医学院药物研究所, 北京 100050
摘要:
JAK-3激酶(Janus kinase 3)作为酪氨酸蛋白激酶家族成员,在JAK-STAT(Janus kinase-signal transducerand activator of transcription)信号通路中起着非常重要的作用,研究证实JAK-3活性的调控在多种疾病的治疗中起着关键作用,针对该激酶的抑制剂已经有许多相关研究,并有多个JAK-3激酶抑制剂进入临床研究,表现出很好的JAK-3选择性和抑制活性,其中tofacitinib等抑制剂已经通过临床试验,被批准用于类风湿性关节炎的治疗。很多JAK-3抑制剂表现出良好抑制活性的同时,伴有一定的不良反应,有待于改进。本文综述了JAK-3激酶的结构功能以及JAK-3激酶抑制剂的研究进展,为后续研究提供参考。
关键词:    酪氨酸蛋白激酶      JAK-3      激酶抑制剂      类风湿性关节炎     
Research progress of JAK-3 kinase and its inhibitors
YIN Yuan1, ZHANG Tian-tai2, ZHANG Da-yong1
1. Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing 210009, China;
2. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
JAK-3, a member of the Janus kinase family, is a protein tyrosine kinase, which plays an important role in the JAK-STAT signaling pathway. Previous studies showed that regulation of JAK-3's activity plays a crucial role in the treatment of diseases such as rheumatoid arthritis. Many reports have been published with a focus on selective JAK-3 inhibitors, some of which showed excellent JAK-3 selectivity and inhibitory activities. Among the JAK-3 inhibitors reported, tofacitinib has satisfactory therapeutic benefits in the clinical trials, and has been approved for treatment of patients with rheumatoid arthritis. However, some JAK-3 inhibitors exhibited moderate to severe side effects, which need to be controlled by drug improvement. In order to pave the way for improvement of current JAK-3 inhibitors and development of new JAK-3 inhibitors, we provide an outline of the structure of JAK-3 and strategies in development of its inhibitors.
Key words:    tyrosine protein kinase    JAK-3    kinase inhibitor    rheumatoid arthritis   
收稿日期: 2016-01-30
DOI: 10.16438/j.0513-4870.2016-0087
基金项目: 国家自然科学基金资助项目(81573445,81172934).
通讯作者: 张天泰, 张大永
Email: ttzhang@imm.ac.cn;zhangdayong@cpu.edu.cn
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