Fig. 6.

INK128 is superior to AZD2014 showing in vivo efficacy alone and combined with dasatinib. (A) Dose response curves for AZD2014 (left) and INK128 (right) were determined for NF2-null Ben-Men-1 and primary MN lines (MN621 and MN626) treated for 72 h with 0–10 µM of indicated drugs (9 dilution points, 3-fold serial dilution). Absolute IC50 (Abs IC50) is shown. Results were plotted as % viability relative to DMSO controls and are presented as ± SEM (3 replicates/dose). (B, C) Treatment of MN lines Ben-Men-1 (B) and MN621 (C) using dasatinib, singly and combined with AZD2014 (left) or INK128 (right), show relative changes in percent proliferation rate (%PR) at D3 where data are normalized to D0 (%PR = 0). Each group represents DMSO (d) or single dasatinib doses (Das: 0–1.1 µM, bracketed at bottom) in combination with increasing doses of AZD2014 or INK128 (see plot key). Error bars, mean ± SD; *P < 0.05 (compared with DMSO). (D, E) Antitumor activities of INK128, dasatinib, and their combination were determined using an orthotopic, quantifiable meningioma model.²¹ Shown are representative bioluminescence images of groups of Ben-Men-1-LucB meningioma-bearing mice at pretreatment or after 14 weeks (wks) posttreatment with vehicle, dasatinib, INK128, or INK128/dasatinib (D). Tumor-emitted bioluminescence signals at each indicated timepoint following treatment were quantified and mean normalized bioluminescence signals from each treatment group were calculated and shown with standard deviations (E).