Extended Data Fig. 10: Characterization of the in vivo pan KRAS inhibitor BI-2493.
From: Pan-KRAS inhibitor disables oncogenic signalling and tumour growth
a, Chemical structure of BI-2493. b, Co-crystal structure of KRAS G13D with BI-2493. c,d, CALU1 cells (c) or RASless MEFs expressing the indicated RAS isoforms (d) were treated as shown and analyzed by RBD pulldown and immunoblotting. A representative of two independent repeats is shown. e, The indicated cancer cell lines were treated as shown for 72 h. Viable cells were determined by ATP-glow (mean ± s.e.m., n = 3). f,g, Effect of KRASi-treatment (1 µM) across a panel of 404 kinases (f) or 38 targets commonly used in safety profiling (g). KRAS was not part of the assay and included only as a reference. h–j, GP2D (h, i, j) or other (i) xenograft bearing mice were treated with BI-2493 (10–90 mg/kg, p.o. twice a day). Plasma (h, i) or tumors (h, j) from treated mice were used to determine the concentration of BI-2493 or the effect on inhibition of the noted ERK signaling intermediates. h: mean ± s.e.m (n = 4), j: median, 95% confidence interval and range are shown (n = 4).
