Figure 1.
PF-06463922 exhibits superior inhibitory activity against all tested ALK-TKD variants. In vitro inhibition profiles of purified unphosphorylated ALK-TKD protein (at 50 nM) harboring the noted mutations with A. crizotinib and B. PF-06463922. Inhibitor concentration was varied from 0 to 25,600 nM, with ATP present at 2 mM, and substrate peptide was held at 0.5 mM, as described (11). Results are plotted as mean ± SD for at least three independent experiments. As discussed in the text, the IC50 values obtained in this experimental format correspond to Ki values in the 6–10 nM range for crizotinib, and the 0.2 nM range for PF-06463922.