C 176

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

Signaling Pathways >> Immunology/Inflammation >> STING

Research Areas >> Inflammation/Immunology

STING[1].

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. We next conducted a three-month trial with C-176 in Trex1−/− mice, which demonstrated marked amelioration of various signs of systemic inflammation[1].

Mice[1] C57BL/6J mice are used in the study. For the pharmacokinetic studies, wild-type mice are injected intraperitoneally with 750 nM C-176 per mouse in 200 μL corn oil. To assess the in vivo inhibitory effect of C-176, wild-type mice (8-12 weeks of age) are injected either with vehicle or C-176. To assess the in vivo inhibitory effect of H-151, wild-type mice are injected intraperitoneally with 750 nM H-151 per mouse in 200 μl 10% Tween-80 in PBS. After 1 h CMA (112 mg/kg) is administered, and after 4 h mice are euthanized and the serum is collected. The efficacy study in Trex1−/− mice is conducted as follows: mice (2-5 weeks of age) are injected with 7.5 μL of C-176 or DMSO dissolved in 85 μl corn oil twice per day for 11 consecutive days. Mice are euthanized by anaesthetization in a CO2 chamber followed by cervical dislocation[1].

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

CCCP | ADU-S100 ammonium salt | DMXAA (Vadimezan) | G10, STING signaling activator | Cyclic-di-GMP | cGAMP | STING agonist-1(compound 3)trihydrochloride