Advances of drugs in targeting cGAS-STING signaling pathway

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.