C-176 (STING inhibitor 1) is a STING inhibitor with selectivity and blood-brain barrier permeability. C-176 inhibits STING-mediated IFNβ production and possesses anti-inflammatory activity.

HCC1806 cells:6.2 μM, HCC1143 cells:9.5 μM, RAW 264.7 cells:1.14 μM, HCC38 cells:8.7 μM

METHODS: HEK293T cells expressing mCherry-STING were transfected with plasmids encoding cdG Syn or RIG-I and an IFNβ luciferase reporter gene, then treated with C-176 (0.01-1.25 µM) to detect IFNβ luciferase activity.
RESULTS: C-176 strongly reduced STING-mediated, but not RIG-I or TBK 1-mediated, IFNβ reporter activity. [1]
METHODS: The rat microglial cell line GMI-R1 was treated with LPS (1 µg/mL) and C-176 (20 µM), and target protein expression levels were measured by Western Blot.
RESULTS: LPS activated the STING signaling pathway. Although the levels of mitochondrial superoxide and STING were not affected by C-176 treatment, the increase in the phosphorylation levels of TBK1 and NF-κB could be significantly reversed by C-176, suggesting that STING signaling could be inhibited by C-176 treatment in GMI-R1 cell line. [2]

METHODS: To investigate the anti-inflammatory activity in vivo, C-176 (750/375 nmol per mouse in corn oil) was injected intraperitoneally into C57BL/6J mice, and CMA (224 mg/kg) was administered either 1 h or 4 h. After 4 h, the mice were euthanized, and the serum was collected for measurement of CMA-induced cytokine levels.
RESULTS: C-176 significantly reduced the CMA-mediated induction of Type 1 IFNs and IL-6 serum levels without significant toxicity. [1]