Figure 3.

M2698 concentrations were higher in the brain than in the plasma of orthotopic U251 glioblastoma models. Mice bearing U251 human glioblastoma orthotopic tumors (n=6 per time point) were treated with a single oral administration of either vehicle or M2698 in vehicle at 25 mg/kg. Plasma, tumor and normal brain samples were obtained 1, 4, 8 and 24-h post-treatment. M2698 concentrations were assessed by LC-MS/MS and the proportion of phosphorylated: total S6 (pS6/tS6) in tumor and normal brain (expressed as a percentage of vehicle) was determined by western blot analysis at each time point. h, hours; PD, pharmacodynamics; PK, pharmacokinetics; po, oral administration.