Supplementary Figures S1-S17 from NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations

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Supplementary Figure S1. Chemistry/X-ray. Supplementary Figure S2. Biochemical activity of ALK TKIs. Supplementary Figure S3. Kinome profiling of NVL-655. Supplementary Figure S4. Potency in cell viability assay. Supplementary Figure S5. Maximal effect (Emax) in cell viability assay. Supplementary Figure S6. Cellular activity of NVL-655. Supplementary Figure S7. Comparing NVL-655 and lorlatinib potency. Supplementary Figure S8. Pathway analysis in cell lines. Supplementary Figure S9. Further evidence for on-target activity of NVL-655. Supplementary Figure S10. TRK activity. Supplementary Figure S11. Selectivity for ALK versus TRK using additional assays. Supplementary Figure S12. In vivo studies for ALK fusion with a wild-type kinase domain. Supplementary Figure S13. In vivo studies for ALK fusion with G1202R or I1171N single mutations. Supplementary Figure S14. In vivo studies for ALK fusion with G1202R compound mutations. Supplementary Figure S15. Pharmacodynamic analysis in G1202R compound mutation models. Supplementary Figure S16. Body weight and H&E staining for the YU-1077 intracranial study. Supplementary Figure S17. Estimating TRKB inhibition in humans and mice.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.