Extended Data Fig. 1: A chemical screen identifies small-molecule inhibitors of STING.
From: Targeting STING with covalent small-molecule inhibitors
a, Screening workflow. HEK mC-STING, HEK293T cells expressing mCherry–STING. b, Left, summary of the primary screen. Mean of normalized values for IFNβ luciferase activity in cells treated with compound versus cells treated with DMSO. Right, validation of selected candidates from the primary screen. Normalized values for IFNβ luciferase activity (light blue) induced by coexpression of cyclic di-GMP synthase (cdG-Syn) and STING are shown, in comparison to activity triggered by RIG-I (green). c, d, HEK293T cells expressing mCherry–STING were transfected with plasmids that encoded either cdG-Syn or RIG-I, as well as an IFNβ luciferase reporter, and then treated with C-178 or C-176 (1.25 μM–0.01 μM), after which IFNβ luciferase activity (c) or cell viability (using the CellTiter-Blue assay) (d) were measured. e, f, Chemical structures of derivatives of C-176 (e) and their effect (at a concentration of 0.5 μM) on IFNβ luciferase reporter activity triggered by mmSTING or RIG-I (f). Mean ± s.e.m. of n = 3 experiments (c, d, f).
