SN-011 (SN011) is a potent, selective STING antagonist with IC50 of 76 nM (STING signaling inhibition). SN-011 binds with higher affinity (Kd=4.03 nM) to the cyclic dinucleotide (CDN)-binding pocket of STING than endogenous 2'3'-cGAMP (Kd=9.23 nM). SN-011 (1 μM) significantly suppresses the induction of Ifnb, Cxcl10, and Il6 mRNA in MEFs activated by various canonical STING stimulators (ISD, HT-DNA, HSV-1, c-di-GMP, and 2′3′-cGAMP). SN-011 specifically inhibits STING activation and STING-dependent signaling. SN-011 suppresses systemic inflammation and death in Trex1−/− mice.
