Orally bioactive STING antagonist VS-X4 ameliorates STING-mediated autoimmune disease. (A) IC₅₀ of VS-X4 in THP-1 and RAW264.7 cells treated with 10 μM 2′-5′-cGAMP. (B) IC₅₀ of VS-X4 and H-151 in MEFs or THP-1 treated with 10 μM 2′-5′-cGAMP. (C) Survival of Trex1^−/− mice treated with vehicle or VS-X4 intraperitoneally at the indicated doses. Log-rank (Mantel–Cox) test. *P < 0.05; ns, not significant. (D) Serum cytokines in Trex1^−/− mice treated with vehicle or VS-X4 were measured at 8 wk after treatment. Data are shown as the mean ± SEM. (E) Unpaired Student’s t test. *P < 0.05; **P < 0.01. (E) Serum autoantibodies in Trex1^−/− mice treated with vehicle or VS-X4 were analyzed using an autoantibody microarray. (F) Survival of Trex1^−/− mice treated with vehicle or VS-X4 orally. Log-rank (Mantel–Cox) test. *P < 0.05. (G) H&E staining of Trex1^−/− mouse hearts treated with vehicle or VS-X4.