Extended Data Fig. 1: NVS-STG2 is an allosteric small molecule human STING agonist.
From: Activation of human STING by a molecular glue-like compound
a, cGAMP (blue circle, n = 14 independent samples), but not NVS-STG1 (green triangle, n = 2 independent samples), induces a dramatic (>10 °C) thermal shift in human STING C-terminal LBD (155-341) in differential scanning fluorimetry as compared to DMSO treated samples (red square, n = 14 independent samples). b, NVS-STG1-4 compound activity in comparison to cGAMP dose response curve in the activation of human STING in the THP1-Dual reporter cell line (n = 2 independent samples in each compound dose). c and d, STING LBD mutants Y240C (triangle) and R238A (square) lose response to cGAMP entirely but retain full response to NVS-STG2 (mean +/− SD, n = 3 independent samples in each compound dose). e, cGAMP activates human STING (solid circle), mouse STING (solid square), as well as a fusion STING with human STING N-terminal TMD (1-153) and mouse C-terminal LBD (153-378) (empty circle), mean +/− SD, n = 3 independent samples in each compound dose. f, Mouse LBD selective ligand DMXAA activates mouse STING (solid square), as well as a fusion STING with human STING N-terminal TMD (1-153) and mouse C-terminal LBD (153-378) (empty circle), but not human STING (solid circle), mean +/− SD, n = 3 independent samples in each compound dose. g, Mouse STING C95R mutant was not sufficient to render human STING selective NVS-STG2 active toward mouse STING (mean +/− SD, n = 3 independent samples in each compound dose).
