Fig. 1.

BCR-ABL inhibitory activity of ON012380. (A) Structure of ON012380. (B and C) Ten nanograms of recombinant BCR-ABL protein was mixed with different concentrations of the indicated inhibitor, and kinase assays were performed by using Crk as a substrate to measure autophosphorylation and substrate (Crk) phosphorylation. (D) BCR-ABL kinase assays were performed as described in Materials and Methods by using c-Crk as a substrate. The reactions mixtures were spotted onto strips of P81 phosphocellulose paper, washed, and counted. In experiments for which a mixture of imatinib and ON012380 was used, the reaction mixtures contained a constant amount of imatinib (10 nM) and various amounts of ON012380. The values from individual samples were analyzed and plotted as a function of drug concentration. Data points represent an average of three independent experiments performed in duplicate.