Fig. 1.
Development of the ROS1/NTRK inhibitor DS-6051b and the efficacy of DS-6051b in vitro. a Chemical structure of DS-6051b. b In vitro kinase assay in the presence of DS-6051b and the indicated recombinant ROS1 or NTRK family kinases. The calculated IC50 values are indicated. c In vitro kinase assay in the presence of 0.2 μM DS-6051b across 160 kinases at 1 mM ATP. Percentage of kinase inhibition by DS-6051b is shown in the bar graph. d, e Sensitivity of CD74-ROS1 induced or parental Ba/F3 cells (d) and HCC78 cells (e) to crizotinib or DS-6051b. The cells were treated with a range of inhibitor doses for 72 h. Parental Ba/F3 cells were treated with inhibitors in the medium containing IL-3. Cell viability was assessed using CellTiter-Glo assay. f, g Inhibition of ROS1 phosphorylation by ROS1 inhibitors in CD74-ROS1−expressing Ba/F3 cells (f) and HCC78 cells (g). Both the cell lines were treated with increasing concentrations of inhibitors for 2 h. The cell lysates were then immunoblotted to detect indicated proteins