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靶向cGAS-STING信号通路的药物研究进展
投稿时间:2019-11-24  修订日期:2019-11-28  点此下载全文
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作者单位E-mail
梅家豪 中国药科大学 meijiahao@stu.cpu.edu.cn 
洪泽 中国药科大学 hongze@cpu.edu.cn 
王琛 中国药科大学 cwang1971@cpu.edu.cn 
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
中文摘要:病原微生物的入侵和细胞受损导致细胞质中DNA异常聚集,cGAS-STING信号通路识别细胞质中的DNA,激活机体固有免疫和适应性免疫反应,进而清除入侵病原体并维持细胞稳态。cGAS-STING信号通路调控紊乱将导致病原体感染,以及肿瘤和自身免疫疾病等多种疾病发生和发展,因此靶向cGAS和STING蛋白进行的药物开发具有十分重要的临床价值,在近年来受到制药企业和科研院所广泛关注。本文我们将阐述cGAS-STING信号通路介导的固有免疫反应及其在疾病进展中发挥的作用,聚焦于靶向cGAS和STING蛋白的激动剂和抑制剂的研究进展,为后续相关的药物研发提供参考。
中文关键词:固有免疫  cGAS  STING  激动剂  抑制剂  药物开发  
 
Advances in drug discovery targeting the cGAS-STING pathway
Abstract:cGAS-STING signaling senses and responds to cytosolic DNAs associated with pathogenic microbes invasion and cellular damage, which activate innate and adaptive immune responses to eradicate infection and maintain cellular homeostasis. Increasing insights have indicated that aberrant cGAS-STING signaling leads to a variety of diseases, including microbial infection, tumorigenesis and metastasis, autoimmune diseases. Biotech-companies and big pharma are currently mobilizing resources to identify leading compounds targeting cGAS and STING, potentially for clinical translation. Here, we review the recent understanding on the pathological mechanisms of the cGAS-STING signaling in relevant diseases, focusing on the discovery of the agonists and antagonists for therapeutically manipulating cGAS/STING-mediated clinical diseases.
keywords:Innate Immunity, cGAS, STING, Agonists, Antagonists, Drug Discovery
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