Figure 6.

Comparison of approved RET inhibitors. (A) Kinome trees showing the percentage of kinase activity inhibition for 76 wild-type tyrosine kinases in the presence of 1 µmol/L inhibitor. Presented kinases are a subset of the panel of 255 kinases as reported in Table S3. The degree of inhibition is shown from grey (least inhibited) to red (most strongly inhibited). (B) Waterfall plots of cellular responses of approved RET inhibitors. Cell lines harboring a RET alteration, NTRK3 fusion, KIT mutation, PDGFRA fusion, FGFR alteration, or FLT3 ITD mutation are indicated in different colors. (C) Dose-response curve overlays of cell viability assay results of the RET inhibitors in the ETV6-NTRK3 fusion-positive cell line AP-1060. (D) Volcano plot comparing the IC₅₀ difference between RET-altered and RET wild-type cell lines for the 34 inhibitors. Green nodes indicate inhibitors which are significantly more potent in RET-altered cell lines compared to RET wild-type cell lines, as determined by MANOVA.