Evaluation of SBI-4668 in U-937 AML cells expressing the SHP2 oncogenic variant G60R.A, cell viability of U-937 AML cells in the presence of various concentrations of SBI-4668 or the SHP2 allosteric inhibitor RMC-4550 after 3 days in culture. Cell viability is shown as a percentage of the DMSO vehicle control, representing the mean ± SD (n = 4) and curve fitted using nonlinear regression (log[inhibitor] versus normalized response, variable slope). B, phospho-ERK1/2 (p-ERK1/2) immunoblot analysis from total cell lysates of U-937 AML cells treated with SBI-4668 at the indicated concentrations or with SHP2 allosteric inhibitor RMC-4550 (RMC, 1 μM) for 24 h. The quantitation of p-ERK1/2 levels is shown as the percentage of the DMSO (vehicle) control and represents data from three independent experiments (mean ± SD). AML, acute myeloid leukemia; DMSO, dimethyl sulfoxide; SHP2, Src-homology 2 dom/ain–containing phosphatase 2.