In vivo efficacy of GNF-7 in a xenotransplantation model and activity against primary AML patient samples. Bioluminescence was measured in untreated and GNF-7-treated NSG (NOD scid gamma) mice injected via tail-vein with human mutant NRAS-expressing MOLT-3-luc+ cells. (A) Bioluminescence values plotted for mice treated with vehicle or 7.5 mg/kg or 15 mg/kg of GNF-7 (once a day, per os). Data are represented as mean ± standard error of the mean. (B) Representative whole-body bioluminescence images of NSG mice treated with vehicle or 7.5 mg/kg or 15 mg/kg of GNF-7 on day10. (C) Survival curve (Kaplan-Meier). Treated groups show prolongation of overall survival compared with vehicle control. (D) On day 15, a femur of mice injected with MOLT-3-luc+ cells and treated with vehicle or 15 mg/kg of GNF-7 was harvested and sectioned. Bone marrow was stained by antiphospho RPS6 antibody and also terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining was performed. (E) Proliferation of primary AML patient samples expressing mutant NRAS and WT FLT3 and mononuclear cells of bone marrow from healthy donors treated with 0.125 μM of GNF-7 for 3 days. Bar represents 100 μm (D). MNC, mononuclear cells. *P < .05; **P < .01; ***P < .001.