FIGURE 2

FIGURE 2

TNO155 synergizes with ALK-TKIs in ALK-mutant neuroblastoma cells. Cell viability (alamarBlue) analysis (A) and determination of drug interaction (B) in neuroblastoma cells with ALK wild-type (WT) or mutant (MUT) status treated with DMSO control, TNO155, ceritinib, or TNO155 plus ceritinib for 72 hours. C, Western immunoblots of Kelly and SH-SY5Y cells treated with TNO155 (1 µmol/L), ceritinib (0.1 µmol/L), or combination for 24 hours. Cell viability analysis (D) and determination of drug interaction (E) in neuroblastoma cells treated with TNO155, lorlatinib, or TNO155 plus lorlatinib for 72 hours. F, Western immunoblots of Kelly and SH-SY5Y cells treated with TNO155 (1 µmol/L), lorlatinib (1 µmol/L), or combination for 24 hours. Drug concentrations are shown in Supplementary Table S1A. Synergy was calculated using the EOB model. EOB scores > 0, synergistic. *, P < 0.05; **, P < 0.01; ***, P < 0.001; n.s., not significant.