Fig. 8.

G chemotype inhibitors show no off-target effect against other nucleotidyl transferase enzymes. a Biochemical off-target assessment of cGAS inhibitors using soluble adenylyl cyclase enzyme. b, c Cellular off-target effect assessment of cGAS inhibitors against OAS proteins using 2 µg ml⁻¹ poly(I:C) as a ligand to stimulate OAS-RNaseL pathway in THP1 cells (b) and primary human macrophages (c). Red bars encompass the degraded rRNAs that were used for the quantification of relative percentage (%) rRNA degradation. d–f Off-target analysis of 5 µM G108, G140, and G150 against cGAS inhibition in primary human macrophage cells differentiated from human blood-derived monocytes using different ligands: 1000 U ml⁻¹ recombinant human interferon-β (IFN-β) (JAK/STAT), or 2 µg ml⁻¹ LPS (TLR4) (n = 3; mean ± S.D. Data shown are representation of two independent experiments (a, b, d–f).)