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. Author manuscript; available in PMC: 2019 Feb 13.
Published in final edited form as: Nat Cell Biol. 2018 Aug 13;20(9):1064–1073. doi: 10.1038/s41556-018-0169-1

Figure 4. SHP2 Inhibition suppresses growth and RAS/MAPK signaling in a range of cancer cell lines driven by KRASG12 mutations.

Figure 4.

(a) and (b) Representative KRASG12C lines, NCI-H358 and MIA PaCa-2, were grown in 2D culture and incubated with increasing concentrations of RMC-4550 for one hour. Cellular lysates were prepared and levels of RAS-GTP (a) and pERK (b) determined. RMC-4550 produced a concentration-dependent reduction in both cellular RAS-GTP and pERK levels. Geometric mean IC50 values for reduction in pERK in NCI-H358 and MIA PaCa-2 cells were 28 nM and 63 nM respectively (n = 4 independent experiments performed in technical duplicate; figures show mean +/− S.D. for pERK and mean +/− S.E.M. for RAS-GTP). (c) NCI-H358 cells were grown on ULA plates as spheroids. After 5 days in culture, spheroids were treated with RMC-4550 or staurosporine, as a positive control, and assayed for caspase 3/7 activity after 20 hours (n = 3 independent observations; figure shows mean +/− S.D.) Source data is provided in Supplementary Table 9.