Background:

C-176 is a strong and covalent mouse STING inhibitor.

C-176 strongly reduces STING-mediated, but not RIG-I- or TBK1-mediated, IFNβ reporter activity. Pretreatment with C-176 markedly reduce the CMA-mediated induction of serum levels of type I IFNs and IL-6[1].

Notably, treatment of Trex1-/- mice with C-176 resulted in a significant reduction in serum levels of type I IFNs and in a strong suppression of inflammatory parameters in the heart. Wild-type mice on a two-week treatment with C-176 show no evident signs of overt toxicity. The three-month trial conducted with C-176 in Trex1-/- mice demonstrated marked amelioration of various signs of systemic inflammation[1].

[1]. Haag SM, et al. Targeting STING with covalent small-molecule inhibitors. Nature. 2018 Jul;559(7713):269-273.