上市新药抑制JAK3激酶的免疫抑制剂托法替尼.PDFVIP

Drug Evaluation Research 第 37 卷 第 2 期 2014 年 4 月 - 169 - • 上市新药 • 抑制 JAK3 激酶的免疫抑制剂托法替尼 1 2* 2 2 2 1 王澳轩 ，刘冰妮 ，刘 颖 ，刘登科 ，刘 默 ，储德清 1. 天津工业大学 环境与化学工程学院，天津 300387 2. 天津药物研究院 天津市新药设计与发现重点实验室，天津 300193 摘 要：JAK/STAT 是一类重要的细胞因子信号传导通路，与类风湿性关节炎及银屑病等许多疾病相关。美国辉瑞公司研发 的JAK 抑制剂托法替尼（Tofacitinib，CP-690550 ）能选择性抑制JAK3 激酶，美国食品和药物管理局（FDA ）已于2012 年 11 月批准其用于中至重度类风湿性关节炎的治疗。综述其作用机制、合成方法、药效与药动学、临床研究进展，为同类新 药的研发提供参考。 关键词：托法替尼；JAK3 抑制剂；类风湿性关节炎；免疫抑制剂 中图分类号：R976 文献标志码：A 文章编号：1674 - 6376 (2014) 02 - 0169 - 04 DOI: 10.7501/j.issn.1674-6376.2014.02.017 Immune inhibitors of inhibiting JAK3 kinase：Tofacitinib 1 2 2 2 2 1 WANG Ao-xuan , LIU Bing-ni , LIU Ying , LIU Deng-ke , LIU Mo , CHU De-qing 1. School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387, China 2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China Abstract: Janus kinase (JAK)/STAT cytokine signal transduction pathway is believed to play an important role in many diseases，such as rheumatoid arthritis and psoriasis. Tofacitinib (CP-690550) is a selective inhibitor of JAK3 kinase developed by Pfizer Inc.. The U.S. Food and Drug Administration approved tofacitinib for the treatment of moderate to severe rheumatoid arthritis disease in November 2012. The mechanism, synthetic method, efficacy, pharmacokinetics, and clinical research progress of tofacitinib have been summarized in the paper. We would like to provide some reference for the research and development of congeneric new drugs. Key words: Tofacitinib; JAK3 inhibitor; rheumatoid arthritis; immunoinhibitor