STING-IN-8 (Compound 15b) is a potent inhibitor of the stimulator of interferon genes (STING), with an IC50 value of 0.121 μM in humans and 0.033 μM in mice. This compound effectively inhibits STING signaling induced by MSA-2 or 2',3'-cGAMP, as well as the levels of immune and inflammatory cytokines in human and mouse cells. STING-IN-8 shows significant potential for research in STING-related inflammatory and autoimmune diseases.

STING-IN-8 (0.1, 0.3, 1, 3 μM, 5 h) inhibits the upregulation of p-TBK1 and p-IRF3 induced by MSA-2 (10 μM) or 2’, 3’-cGAMP (10 μM) in human and mouse cells. In the THP1-Dual and RAW-Lucia cell lines, STING-IN-8 demonstrates negligible cytotoxicity with a CC50 of 30 μM. Additionally, it effectively inhibits downstream immune-inflammatory cytokines of STING in human and mouse immune cells at concentrations of 0.3, 1, 3 μM and 0.1, 1, 3 μM, over 9 hours.

STING-IN-8, administered intraperitoneally at a dose of 10 mg/kg, effectively suppresses the downstream cytokines of STING in mice stimulated with MSA-2. A daily dose of 10 mg/kg via intraperitoneal injection for two consecutive weeks significantly reduces elevated inflammatory cytokines in mice experiencing Trex1 loss of function.