JAK3 inhibitor VI is a mutant specific inhibitor for epidermal growth factor receptor with the gatekeeper mutation T790M

Figure 1 Janus kinase 3 inhibitor VI selectively inhibits kinase activity of the epidermal growth factor receptor gatekeeper mutant T790M/L858R in vitro. A, B: Chemical structures of JAK3 inhibitor VI (A) and Gö7874 (B) are shown; C: Effects of JAK3 inhibitor VI on kinase activities of WT, L858R, and T790M/L858R EGFRs were compared. Recombinant EGFR kinase domains were treated using JAK3 inhibitor VI at 10 μmol/L, and phosphorylation was initiated by adding ATP in the presence of an artificial substrate peptide. Phosphorylation levels were measured by ELISA using an anti-phosphotyrosine antibody. Error bars indicate SEM (n = 4); ^aP < 0.05. NS: Not significant; EGFR: Epidermal growth factor receptor; JAK3: Janus kinase 3.