RESEARCH ARTICLE TAE226, a Bis-Anilino Pyrimidine Compound, Inhibits the EGFR-Mutant Kinase Including T790MMutant to Show Anti-Tumor Effect on

TAE226, a bis-anilino pyrimidine compound, has been developed as an inhibitor of focal ad-hesion kinase (FAK) and insulin-like growth factor-I receptor (IGF-IR). In this study, we in-vestigated the effect of TAE226 on non-small-cell lung cancer (NSCLC), especially focusing on the EGFRmutational status. TAE226 was more effective against cells with mu-tant EGFR, including the T790Mmutant, than against cells with wild-type one. TAE226 pref-erentially inhibited phospho-EGFR and its downstream signaling mediators in the cells with mutant EGFR than in those with wild-type one. Phosphorylation of FAK and IGF-IR was not inhibited at the concentration at which the proliferation of EGFR-mutant cells was inhibited. Results of the in vitro binding assay indicated significant differences in the affinity for TAE226 between the wild-type and L858R (or delE746_A750) mutant, and the reduced af-finity of ATP to the L858R (or delE746_A750) mutant resulted in good responsiveness o