Fig 6. Brigatinib, dasatinib, simvastatin and combination treatments in the schwannoma mouse model.

(A) Single-dose pharmacokinetics of compounds in PostnCre; Nf2^flox/flox mice. Plasma compound concentrations were measured at baseline, 1, 2, 4, 8 and 24 hours after administering a single oral dose to n = 3 PostnCre; Nf2^flox/flox mice. Parameters were calculated using a noncompartmental NCA-xls using PK add ins. (B) Volume of dorsal root ganglia (DRG) was measured post-mortem. All treatment groups had significantly smaller DRG volume when compared to vehicle, and brigatinib-treated DRGs showed the greatest reduction. One-Way ANOVA with Dunnett’s multiple comparison’s test; p = 0.0001(****), p = 0.0007(***), p<0.05(*). (C) Representative hematoxylin and eosin stained DRGs following 12 weeks of continuous treatment with the indicated drugs.