Extended Data Fig. 3: AMG 510 covalently modifies KRAS(G12C) in tumours and inhibits signalling in vivo.
From: The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity
a–d, Mice bearing MIA PaCa-2 T2 (a, c, d) or CT-26 KRASG12C (b) tumours were treated orally with a single dose of vehicle (black bars) or with the indicated doses of AMG 510 (blue bars). Tumours were collected 2 h later (a, b) or over time as indicated (c, d) and levels of p-ERK were measured. AMG 510 concentrations in plasma (red triangles) or tumours (black open circles). Data are mean ± s.e.m., n = 3 mice per group; ****P < 0.0001, ***P < 0.001, **P < 0.01 compared with vehicle; one-way ANOVA followed by Dunnett’s multiple-comparison test. e, Half-life determination of KRAS(G12C) in MIA PaCa-2 and NCI-H358 cells by SILAC. Data are mean ± s.d., n = 3 replicates. f, g, AMG 510 treatment results in covalent modification of KRAS(G12C) that inversely correlates with p-ERK inhibition in MIA PaCa-2 T2 tumours. Data are mean ± s.d., n = 3 mice per group.
