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. Author manuscript; available in PMC: 2022 Aug 1.
Published in final edited form as: Mol Cancer Ther. 2021 Dec 14;21(2):336–346. doi: 10.1158/1535-7163.MCT-21-0395

Figure 4. Activity of first and next-generation ROS1 inhibitors against spectrum of ROS1 intracellular mutations in CD74-ROS1 and EZR-ROS1.

Figure 4.

A, Dose response cell viability assays of clinically relevant (S1986F, F2004C, F2004V, L2026M, G2032R, D2033N and L2086F compared to wildtype) ROS1 kinase domain mutations in Ba/F3 CD74-ROS1 cells. Average ± SEM shown for all data. B & C, Immunoblotting of Ba/F3 CD74-ROS1L2086F and EZR-ROS1L2086F cells treated for 6 h with 100 nM of indicated inhibitors. Phosphorylated and total ROS1 and ERK1/2 are shown. D & E, Heat map of IC50 values (nanomolar) of crizotinib, entrectinib, lorlatinib, repotrectinib, cabozantinib and foretinib for Ba/F3 CD74-ROS1 (D) and EZR-ROS1 (E) mutant cell lines. IC50 are average of two to four replicates for each mutant and each inhibitor. Color scale for heatmap in indicated in the figure.