Biochem/physiol Actions

C-176 is a potent and selective inhibitor against murine, but not human, stimulator of interferon genes (STING) via covalent modifiation of mSTING Cys91. C-176 inhibits STING-mediated IFNβ reporter activity (IC₅₀ ﹤50 nM) without affecting RIG-I, and blocks (1 µM) downstream TBK1 phosphorylation induction by STING agonist CMA (1.4 h) in mSTING-expressing HEK293T cells. C-176 markedly reduces CMA-induced serum IL-6 & type I IFNs in mice (by ≥85% 4 h post CMA; 750 nmol C-176/mouse i.p. 1 or 4 h prior to 224 mg/kg CMA) and significantly ameliorates the autoinflammatory severity in Trex1−/− mice.