自身免疫性疾病：胞内信号通路及相关靶向治疗药物.pdf

PROGRESS IN PHARMACEUTICAL SCIENCES 2016,40 4 :310-314 310 ( ) 自身免疫性疾病：胞内信号通路及相关靶向治疗药物 刘丽丽，毛艳艳，高柳滨* ( 中科院上海药物所信息中心情报研究部，上海 201203) [ 摘要 ] 细胞因子调控人体免疫应答，在自身免疫性疾病治疗中发挥了重要作用。以细胞因子为靶标的一系列生物制剂在自身免疫性疾 病的治疗中取得了前所未有的成功，但并未很好地满足疾病治疗需求。寻找新型治疗手段仍是自身免疫病治疗领域的迫切需求。细胞因 子通过调控下游胞内信号通路如两面神激酶（Janus kinase，JAK）及信号转导和转录激活因子（signal transducer and activator of transcription，STAT）通路等发挥信号转导功能。对胞内通路的抑制可以实现对细胞因子的阻断作用从而治疗疾病，JAK 抑制剂已被证实 对类风湿性关节炎及其他炎症类疾病有效，STAT 通路也被认为是未来类风湿性关节炎治疗的一个热点方向。靶向胞内通路已为未来自身免 疫性疾病治疗提供了新的思路。结合文献信息及数据库，对目前靶向胞内 JAK 和 STAT 信号通路的自身免疫性疾病治疗药物的研发现状进 行简要介绍。 [ 关键词 ] 自身免疫性疾病；两面神激酶；信号转导和转录激活因子；胞内信号通路 [ 中图分类号 ] R979.5 [ 文献标志码 ] A [ 文章编号 ] 1001-5094（2016）04-0310-05 Autoimmune Disease: Intracellular Signaling Pathways and Targeted Therapeutics LIU Lili, MAO Yanyan, GAO liubin (Intelligence Research Department, Information Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China) [Abstract] Cytokines regulate human immune response and play an important role in the treatment of autoimmune diseases. Although a series of biological agents targeting cytokines have achieved unprecedented success in the treatment of immune-mediated diseases, they hardly induce complete remission in all patients. Consequently, there is still an urgent need to develop new treatments for autoimmune diseases. Cytokines conduct signals through regulating downstream intracellular pathways such as Janus kinase (JAK) and signal transducer and activator of transcription (STAT). Thus, inhibition of intracellular pathways can block cytokines for disease treatment. JAK inhibitors have been proved effective for the treatment of rheumatoid arthritis and other inflammatory diseases, STAT