cGAS-STING信号通路相关靶向药物的研究进展  

Research Progress of Targeted Drugs Related to cGAS-STING Signaling Pathway

作　　者：张颖[1] 李真[1] 王全逸 王琛 ZHANG Ying;LI Zhen;WANG Quanyi;WANG Chen(School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China;State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009 [2]中国药科大学天然药物活性组分与药效国家重点实验室,江苏南京210009

出　　处：《药学进展》2022年第8期564-576,共13页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金(No.31730018,No.82171751)。

摘　　要：环磷酸鸟苷-腺苷一磷酸合成酶(cyclic guanosine monophosphate-adenosine monophosphate synthase,cGAS)-干扰素基因刺激因子(stimulator of interferon genes,STING)信号通路对于感知细胞质中异常积聚的DNA至关重要。cGAS与异常DNA结合后,生成第二信使环化二核苷酸。环化二核苷酸可激活下游STING,从而诱导Ⅰ型干扰素等炎症细胞因子的表达,最终启动免疫应答。该信号通路能够在抗病原体感染、抗肿瘤等方面发挥重要的免疫作用,因此开发靶向该信号通路的药物,具有重要的临床应用价值。综述将对c GAS-STING信号通路和靶向c GAS-STING药物的最新研究进行总结和讨论,以期为筛选c GAS-STING信号通路的抑制剂和激动剂,并进一步研发成临床药物提供理论依据和实践参考。Cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway is critical for sensing abnormal accumulation of DNA in the cytoplasm.cGAS binds to abnormal DNA to generate a second messenger circular dinucleotide.Circular dinucleotide activates the downstream STING,which induces the expression of inflammatory cytokines such as type I interferon,and initiates an immune response.cGAS-STING signaling pathway performs an important immune function in resisting pathogen infection and anti-tumor.Therefore,the discovery of drugs targeting this signaling pathway is of great value in clinical application.This review summarizes the latest research on cGAS-STING signaling pathway and drugs targeting this signaling pathway,so as to provide theoretical basis and practical reference for further development of targeted drugs from cGAS-STING pathway-related inhibitors and agonists.

关 键 词：cGAS-STING信号通路 激动剂 抑制剂 药物研发 

分 类 号：R392.1[医药卫生—免疫学]