选择性酪氨酸激酶2抑制剂的研究进展  

Research Progress in Selective Tyrosine Kinase 2 Inhibitors

作　　者：王力勋 朱佩钰 周金培[2] 张惠斌[1] WANG Lixun;ZHU Peiyu;ZHOU Jinpei;ZHANG Huibin(Center of New Drug Research,China Pharmaceutical University,Nanjing 210009,China;Department of Medicinal Chemistry,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学新药研究中心,江苏南京210009 [2]中国药科大学药物化学教研室,江苏南京210009

出　　处：《药学进展》2022年第5期379-387,共9页Progress in Pharmaceutical Sciences

基　　金：临港实验室资助(No.LG202103-02-08)。

摘　　要：Janus激酶(JAK)通过JAK-信号转导和转录激活因子(STAT)信号通路调控白细胞介素(IL)、干扰素(IFN)等细胞因子的信号传导,在免疫调节中发挥重要作用。JAK家族抑制剂可以用于治疗自身免疫性疾病,然而存在治疗指数狭窄、免疫抑制等安全性问题。酪氨酸激酶2(TYK2)是JAK家族的成员,参与IL-23、IL-12和I型IFN的信号传导。选择性抑制TYK2能够尽可能减少潜在的副作用,在临床上更加安全有效,选择性TYK2抑制剂在自身免疫性疾病的研究也越来越深入。对TYK2的结构特点、作用机制、信号通路及其抑制剂的研究进展进行综述,以期为代谢性疾病药物的研究提供参考。The Janus kinases(JAK) modulate the signal transduction of cytokines such as interleukins(IL) and interferons(IFN) through Janus kinase/signal transducers and activators of transcription(JAK/STAT) pathway. JAK inhibitors can be used to treat autoimmune diseases, however, due to the narrow therapeutic index and immunosuppression, researchers turned to tyrosine kinase 2, which is involved in the signal transduction of IL-23, IL-12 and type I IFNs as a member of the Janus kinases. Selective tyrosine kinase 2 inhibitors could reduce the occurrence of side-effects and are more secure in clinic, so the research on selective TYK2 inhibitors in autoimmune diseases have further developed and deepened. Herein, we reviewed the structural characteristics, mechanism, signaling transduction pathways and the development process of selective TYK2 inhibitors to provide reference for the research on metabolic disease drugs.

关 键 词：JANUS激酶 酪氨酸激酶2 抑制剂 自身免疫性疾病 

分 类 号：R593.2[医药卫生—内科学]