Fig. 3
Antitumor, survival, and metabolic effects of MC180295 and its enantiomers, MC180379 and MC180380. A Antitumor effects of MC180295, MC180379, and MC180380. NSG mice were inoculated (s.c.) with 2 × 106 SW48 cells. Eleven days later, when tumors were palpable, 20 mg/kg MC180295, MC180379, MC180380, or vehicle were administered (i.p.) every other day (q.o.d.). Tumor sizes were measured using a caliper. B SW48 mouse survival with q.o.d. i.p administration of 20 mg/kg MC180379 or MC180380. C Antitumor effects of MC180379 and MC180380. NSG mice were inoculated (s.c.) with 1 × 106 HT29 cells. Twelve days later, when tumors were palpable, 20 mg/kg MC180379, MC180380, or vehicle were administered (i.p.) q.o.d. Tumor sizes were measured using a caliper. D HT29-xenografted mouse survival following (i.p.) q.o.d. dosing with 20 mg/kg MC180379 or MC180380. E NSG mice were inoculated (i.p.) with 5 × 105 MV4-11-luc cells. Four days later, when substantial tumor burden was evident by bioluminescence imaging, MC180379, MC180380, or vehicle were administered (i.p.) q.o.d at 20 mg/kg. Luciferase expression was quantified and calculated. F Mouse survival in days. MC180380 significantly extended survival in i.p. MV4-11 model mice. G In vitro liver microsome stability and rat hepatocyte/Sprague–Dawley stability assay comparing MC180379 to MC180380. The dog breed was beagle and the mouse microsome strain was CD-1. All sexes (including the hepatocytes) were male except the human microsomes which were mixed gender. Significances were calculated using log-rank (Mantel-Cox) or Student’s t tests. Data are shown as means ± SEMs. *p < 0.05, **p < 0.01, ***p < 0.001