Extended Data Fig. 8: ARAF N terminus loss boosts effect of RAF dimer inhibitors.
From: Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance
a, A549 and MIA PaCa-2 isogenic clones were subjected to western blot. b, Isogenic A549 cells were subjected to endogenous CRAF immunoprecipitation. c, Genetically engineered MIA PaCa-2 cells were treated with Belvarafenib or Naporafenib for 72 hours. Cell survival was normalized to untreated controls, n = 6. Drug concentrations inducing 50% inhibition in survival (IC50 nmol/L) are indicated. d, Genetically engineered MIA PaCa-2 cells were treated with Belvarafenib or Naporafenib for 1 hour. ERK pathway activities were examined by western blot. e, Genetically engineered MIA PaCa-2 cells treated with the indicated compounds were subjected for growth analysis, n = 6. f, Colony formation assay in the engineered MIA PaCa-2 cells treated with either vehicle, Belvarafenib or Naporafenib. The colonies were stained with crystal violet. g, Engineered MIA PaCa-2 cells were subcutaneously injected into nude mice. Mice were treated with either vehicle, Belvarafenib (30 mg/kg once a day) or Naporafenib (100 mg/kg once a day). Bars, mean ± SEM, n = 5. Immunoblots are representative of three independent experiments in a, b, d. Error bars denote the mean ± SD (biological replicates) in c, e.
