cGAS-STING通路异常激活及其抑制剂在免疫和炎症疾病中的研究进展  

Advances in cGAS-STING pathway and its inhibitors in immune and inflammatory diseases

作　　者：李文欣 张贺峰 谢作权 段文虎 LI Wen-xin;ZHANG He-feng;XIE Zuo-quan;DUAN Wen-hu(Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China)

机构地区：[1]中国科学院上海药物研究所,上海201203

出　　处：《中国药理学通报》2023年第11期2001-2005,共5页Chinese Pharmacological Bulletin

基　　金：临港实验室“肿瘤领域原创新药创制”项目(No LG202103-02-08)。

摘　　要：cGAS-STING通路是针对多种类型病原体进行免疫防御的主要途径之一,环鸟苷酸-腺苷酸合成酶(cGAS)通过识别细胞质的DNA分子,催化生成第二信使cGAMP(cyclic GMP-AMP)与干扰素基因刺激因子(STING)结合,诱导产生I型干扰素(IFN-I),激活机体先天免疫系统。cGAS-STING通路的适当激活有助于机体实现自我保护,因此,近年来STING激动剂在肿瘤免疫治疗的研究中引起了广泛关注,一些候选药物已进入临床研究,用于多种肿瘤治疗。与此同时,cGAS-STING通路异常激活会导致自身免疫性疾病的发生,获得了药物研究者的广泛关注并积极开发其抑制剂。该文总结了cGAS-STING通路的机制和调控位点,概述了cGAS-STING通路相关的免疫和炎症疾病及其抑制剂的研究进展。The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens.cGAS catalyzes the production of the second messenger cGAMP(cyclic GMP-AMP)by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor(STING).The pathway induces the production of type I interferon(IFN-I)and activates the innate immune system.The activation of the cGAS-STING pathway could facilitate self-protection,thus STING agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials.Meanwhile,aberrant activation of cGAS-STING could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors.This paper summarizes the mechanism and regulatory sites of the cGAS-STING pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

关 键 词：环鸟苷酸-腺苷酸合成酶 干扰素基因刺激因子 环状二核苷酸 I型干扰素 抑制剂 免疫疾病 

分 类 号：R-05[医药卫生] R342.4R394.2R593.2R977.6R978.7