2249435-90-1

SN-011 is a stimulator of interferon genes (STING) antagonist.1 It binds to the STING cyclic dinucleotide binding site (Kd = 4.03 nM) and inhibits 2’3’-cGAMP-induced Ifnb expression in mouse embryonic fibroblasts (MEFs), mouse bone marrow-derived macrophages (BMDMs), and human foreskin fibroblasts (HFFs; IC50s = 127.5, 107.1, and 502.8 nM, respectively). SN-011 (1 μM) impairs recruitment of IFN regulatory factor 3 (IRF3) or TANK-binding kinase 1 (TBK1) to the STING signalosome in HEK293T cells overexpressing tagged wild-type or SAVI-linked mutant STING and IRF3 or TBK1, as well as inhibits translocation of STING from the endoplasmic reticulum (ER) to the Golgi induced by herpes simplex virus 1 (HSV-1) in HFFs. In vivo, SN-011 (5 mg/kg) increases survival and reduces Ifnb mRNA levels in the Trex1-/- mouse model of Aicardi-Goutières syndrome, an autoimmune disorder characterized by constitutive activation of cGAS and IFN overproduction.

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1.Hong, Z., Mei, J., Li, C., et al.STING inhibitors target the cyclic dinucleotide binding pocketProc. Natl. Acad. Sci. USA.118(24)e2105465118(2021)