Figure 3. SHP2 inhibition enhances the efficacy of KRASG12C inhibition.
(A) Cell lines were treated with ARS-1620 (1 uM), SHP099 (10 uM), or a combination for 4 or 48 h and lysates were subject to a RAF-RBD pulldown and blot analysis of KRAS, NRAS, HRAS and total RAS as well as pERK, pRSK and GAPDH for input samples. (B) KRASG12C mutant cell lines were treated with ARS-1620 (1 µM), SHP099 (10 µM) or a combination for 0, 4, 24, 48, and 72 h. Blot analysis was performed for pMEK, pERK, pRSK, pAKT, total MYC with GAPDH as a loading control. (C) Densitometry analysis of pERK normalized to GAPDH was performed for all cell lines (D) Quantification of crystal violet stain of cell lines treated with ARS-1620 (1 µM), SHP099 (10 µM), or a combination for 10–14 days, statistical significance was evaluated by Student’s t-test, where *: p<0.05, **: p<0.01, ***: p<0.001, ****: p<0.0001.