Fig. 1: Idronoxil inhibits STING, MAVS and TRIF driven responses.

a Interferon [IFN]-β luciferase expression in HEK293T mSTING cells overexpressing cGAS treated O/N with the indicated compounds (n = 3 independent experiments). b IFN-stimulated response element [ISRE]-Luciferase expression in L929 cells after 7 h stimulation with the mouse STING agonist DMXAA at 20 μg/ml and the indicated compounds (n = 3 independent experiment for all except Quercetin n = 2 independent experiments). c IFN-β (right) and IP-10 (left) protein levels in THP-1 monocytes after 6 h stimulation with the human STING agonist GSK3 at 100 nM and treatment with indicated idronoxil (IDX) doses. Right: 2.5 μM IDX was used (n = 3 independent experiments). d RNA sequencing analysis of the top 20 murine ISGs⁶¹ in RNA lysates from Trex1^Q98X bone marrow-derived macrophages [BMDMs] treated O/N with 1.25 μM IDX (heat map of log₂ expression relative to the average across all samples; significant genes are indicated with an asterisk) (n = 3 independent animals [C1–C3]). NT is non-treated. e Immunoblot of wild-type [WT] immortalised bone marrow-derived macrophages [iBMDMs] stimulated with 50 μg/ml DMXAA (STING) for the indicated times ±2.5 μM IDX (1 representative blot of 3 independent experiments shown). Molecular weight markers are shown in kDa. A doublet of STING bands appears upon STING activation. Phosphorylated proteins are indicated with [P]. f Immunoblot of wild-type and Tbk1^KO iBMDMs stimulated with 200 ng/ml LPS (TLR4) ± 2.5 μM IDX treatment for the indicated time (1 representative blot of 3 independent experiments shown). Phosphorylated proteins are indicated with [P]. Molecular weight markers are shown in kDa. g IFN-β luciferase expression in p125HEK cells treated with indicated dose of IDX and stimulated O/N with 50 ng/ml of 3p-hpRNA (RIG-I agonist [RIG-Ia]) (n = 3 independent experiments). h RT-qPCR analyses of IFNB1/18S, RSAD2/18S and IFIT1/18S in RNA lysates from primary human bronchial epithelial cells [PBECs] from 3 independent donors treated with 5 μM IDX or 200 nM MRT, and stimulated 3 h with 1 μg/ml transfected polyI:C (MDA5/RIG-I), 25 μg/ml naked polyI:C (TLR3) or transfected with 2.5 μg/ml ISD70 (cGAS) (n = 3 independent donors). a–c, g, h Data are mean ± s.e.m. c One-way or (h) two-way ANOVA with uncorrected Fisher’s LSD (with single pooled variance) multiple comparisons are shown. a–c, g Non-linear regression analyses are shown. Exact p values are shown for all comparisons. Source data and detailed statistical analyses are provided as a Source Data file.