Extended Data Fig. 3. Activity and specificity of a human cGAS inhibitor TDI-8246 (Related to Fig. 2).

a. Inhibitory effects of TDI-8246 (0.01–100 µM concentration) on human cGAS/HT-DNA-catalyzed conversion of ATP and GTP to produce cGAMP measured by remaining ATP concentrations in the reactions using ATP Glo assay. b. Dose-dependent inhibition of cGAS activity (as measured in a) in response to HT-DNA. IC₅₀ = 8.123 × 10⁻⁸ M. Data are reported as mean ± SD. n = 3 biologically independent samples per condition. c. Quantification of IRF-Lucia luciferase luminescence intensity and NF-κB-SEAP absorbance of WT and Cgas−/− THP-1 dual cells treated with HT-DNA and TDI-8246 as indicated. Data are reported as mean ± SEM. n = 4 biologically independent samples. **** p < 0.0001. Two-way ANOVA followed by Tukey’s multiple comparisons test (n = 4). d. Predicted upstream regulators associated with DEGs in DMSO + tau vs TDI-8246+tau from ingenuity pathway analysis. P-value overlap < 0.05, Activation Z score > 2 or < -2. Right-tailed Fisher’s exact test.