Fig. 2

Evaluation of eight MET-TKIs, including four candidates, against clones with MET D1228X or Y1230X. A The IC₅₀ values (nM) of each drug for Ba/F3 cells harboring METex14 plus the indicated MET secondary mutations are expressed according to the indicated color scale. * indicates Ba/F3 clones generated using the corresponding vectors. Other cell lines were derived by ENU mutagenesis. Growth inhibition curves are summarized in Additional file 2: Fig. S2A and B. B The IC₅₀ values of each drug for cells with each secondary mutation are expressed as fold increases of the IC₅₀ for parental cells with METex14 in dot plots. C Western blot analyses of Ba/F3 cells with METex14 with/without secondary mutations treated with MET-TKIs at the indicated concentrations for 3 h. D The sensitivity index (SI) was defined as the IC₅₀ value divided by the concentration max (C_max) of each drug, which was reported in a clinical study. SI is expressed in a heatmap by the indicated color scales. For cabozantinib, since no PK data at 60 mg/day were available, the values were estimated from those reported at 80 mg/day and 40 mg/day based on previous reports (Kuzrock, R. et al. J Clin Oncol. 2011)