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靶向cGAS-STING信号通路药物的研究进展

梅家豪, 洪泽, 王琛

梅家豪, 洪泽, 王琛. 靶向cGAS-STING信号通路药物的研究进展[J]. 中国药科大学学报, 2020, 51(3): 249-259. DOI: 10.11665/j.issn.1000-5048.20200301
引用本文: 梅家豪, 洪泽, 王琛. 靶向cGAS-STING信号通路药物的研究进展[J]. 中国药科大学学报, 2020, 51(3): 249-259. DOI: 10.11665/j.issn.1000-5048.20200301
MEI Jiahao, HONG Ze, WANG Chen. Advances of drugs in targeting cGAS-STING signaling pathway[J]. Journal of China Pharmaceutical University, 2020, 51(3): 249-259. DOI: 10.11665/j.issn.1000-5048.20200301
Citation: MEI Jiahao, HONG Ze, WANG Chen. Advances of drugs in targeting cGAS-STING signaling pathway[J]. Journal of China Pharmaceutical University, 2020, 51(3): 249-259. DOI: 10.11665/j.issn.1000-5048.20200301

靶向cGAS-STING信号通路药物的研究进展

基金项目: 国家自然科学基金资助项目(No. 81672029)

Advances of drugs in targeting cGAS-STING signaling pathway

Funds: This study was supported by the National Natural Science Foundation of China (No. 81672029)
  • 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,环化核苷酸合成酶(cGAS)通过识别细胞质中的DNA,催化生成第二信使2",3"-cGAMP,将信号传递给下游干扰素基因刺激因子(STING),诱导转录因子IRF3和NF-κB入核,表达和分泌Ⅰ型干扰素等炎症因子,进而激活机体固有免疫和适应性免疫反应。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。本文讨论cGAS-STING信号通路的最新研究进展以及其在不同疾病中发挥的功能,并总结目前已报道的调节cGAS和STING的小分子化合物,为后续相关的药物研发提供理论参考。
    Abstract: Invasion of pathogenic microorganisms and cell damage lead to abnormal accumulation of DNA in the cytoplasm. Cyclic GMP-AMP synthase (cGAS) catalyzes the generation of second messenger 2", 3"-cGAMP by recognizing DNA in the cytoplasm, transmitting signals to downstream stimulators of interferon gene (STING). STING induces the translocation of transcription factors IRF3 and NF-κB into the nucleus to express and secrete inflammatory factors such as type I interferon, which activate the body"s innate and adaptive immune responses. Many studies have indicated that disturbance of cGAS-STING pathway regulation leads to the occurrence and development of various diseases such as microbial infection, tumor and autoimmune diseases. Therefore, the development of drugs targeting cGAS and STING proteins is of great clinical value. This paper reviews the latest research progress of cGAS-STING pathway and its roles in different diseases, and summarizes the small-molecule compounds that have been reported to regulate cGAS and STING, in order to provide theoretical reference for future cGAS-STING pathway-related drug discovery.
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出版历程
  • 收稿日期:  2019-11-23
  • 修回日期:  2020-04-20
  • 刊出日期:  2020-06-24

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