Biochem/physiol Actions
Potent, selective, and non-cytotoxic STING inhibitor that blocks STING signaling and inflammation in both in vitro and in vivo.
SN-011 is a potent, specific, and non-cytotoxic STING antagonist that binds to the STING cyclic dinucleotide (CDN)-binding domain with higher affinity than endogenous 2’3’-cGAMP. It locks the STING dimer in an open, inactive conformation and stalls STING-dependent signaling. SN-011 inhibits 2′3′-cGAMP-induced Ifnb expression (IC50 = 127.5, 107.1, and 502.8 nM in MEFs, mouse bone marrow-derived macrophages (BMDMs), and human foreskin fibroblasts (HFFs), respectively. It also suppresses the secretion of pro-inflammatory molecules in vitro mouse and human models, including HSV-1 infection and Trex1 deficiency in mice. SN-011 blocks the spontaneous activation of GOF STING mutants that cause STING-associated vasculopathy with onset in infancy (SAVI).