cGAS acts as a pattern recognition sensor for cytosolic DNA. Its synthetic product cGAMP activates STING, which induces the interferon response, and production of inflammatory cytokines.

The small molecule Ru.521 inhibits mouse cGAS by binding in its catalytic pocket, but amino acid differences in human cGAS negates Ru.521 binding [1-2].

* Key recommended reading is highlighted with an asterisk

* Goodnow CC. (2021) COVID-19, varying genetic resistance to viral disease and immune tolerance checkpoints. Immunol Cell Biol, 99 (2): 177-191. [PMID:33113212]

* Hertzog J, Rehwinkel J. (2020) Regulation and inhibition of the DNA sensor cGAS. EMBO Rep, 21 (12): e51345. [PMID:33155371]

* Li Z, Cai S, Sun Y, Li L, Ding S, Wang X. (2020) When STING Meets Viruses: Sensing, Trafficking and Response. Front Immunol, 11: 2064. [PMID:33133062]

* Shi F, Su J, Wang J, Liu Z, Wang T. (2021) Activation of STING inhibits cervical cancer tumor growth through enhancing the anti-tumor immune response. Mol Cell Biochem, 476 (2): 1015-1024. [PMID:33141310]

* Wu Y, Li S. (2020) Role of Post-Translational Modifications of cGAS in Innate Immunity. Int J Mol Sci, 21 (21). DOI: 10.3390/ijms21217842 [PMID:33105828]

1. Vincent J, Adura C, Gao P, Luz A, Lama L, Asano Y, Okamoto R, Imaeda T, Aida J, Rothamel K et al.. (2017) Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice. Nat Commun, 8 (1): 750. [PMID:28963528]

2. Zhou W, Whiteley AT, de Oliveira Mann CC, Morehouse BR, Nowak RP, Fischer ES, Gray NS, Mekalanos JJ, Kranzusch PJ. (2018) Structure of the Human cGAS-DNA Complex Reveals Enhanced Control of Immune Surveillance. Cell, 174 (2): 300-311.e11. [PMID:30007416]