Fig. 4: Optimized β-lactone ligands suppress K-Ras(G12S) signaling in cells.
From: Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S)
a, Structures of K-Ras(G12S) ligands G12Si-3, G12Si-4 and G12Si-5. b, Time-dependent covalent modification of recombinant K-Ras(G12S)•GDP protein by 10 µM compound at 23 °C assessed by whole-protein MS (n = 3, replicates are plotted as individual data points). c, Immunoblot of A549 cells treated with 10 µM adagrasib, G12Si-3, G12Si-4 or G12Si-5 for 2 h. Data are representative of two independent experiments. d, Immunoblot of A549 cells treated with various concentrations of G12Si-5 for 2 h. Data are representative of two independent experiments. e, Immunoblot of A549, A375, SW1990 and H358 cells treated with DMSO or 10 µM G12Si-5 for 2 h. Data are representative of two independent experiments. WT, wild-type. f, Relative growth of Ba/F3 parental cells (+10 ng ml−1 IL-3) and Ba/F3:K-Ras(G12S) cells (no IL-3) after treatment with adagrasib or G12Si-5 for 72 h. Data are presented as mean ± s.d. (n = 3) and are representative of four independent experiments.
