SHP099 treatment reduces pErk levels in U2OS cells harboring the weakly stimulating SHP2F285S enzyme (Fig. 6c), with an IC50 for pErk reduction approximately four-fold greater (8 ± 2 μM) than in SHP2WT cells (Fig. 6d; see Supplementary Figs. 5–15 for full lanes associated with western blot data from Figs. 5, 6); in contrast, SHP2S502P displays little, if any, loss of pErk at 50 μM SHP099, and SHP099 does not significantly inhibit Erk phosphorylation in the other cancer mutants investigated. This evidence concerns the gene EIF2AK3 and cancer.