Fig. 2.

KBU2046 inhibits cancer metastasis and prolongs life. a, b Inhibition of PCa metastasis. Cohorts of N = 12 athymic mice bearing human PCa PC3-M cell orthotopic implants (a), or of N = 5 non-tumor bearing athymic mice (b), were treated with KBU2046 incorporated into chow, and resultant lung metastasis (a) or plasma KBU2046 concentration (b) measured. Values are the mean ± SEM. The relationship between dose and metastasis was evaluated by two-sided ANOVA (a). c Comprehensive characterization of KBU2046 pharmacokinetics. CD1 mice were dosed with 100 mg KBU2046/kg via oral gavage or intravenous injection (iv), and blood collected at the indicated time points (data from mice dosed at 25 mg/kg are in Supplementary Fig. 6, and corroborate 100 mg/kg findings). For each route and time point, N = 3 mice were sampled. Individual data points are the resultant plasma concentrations from individual mice, and are the mean of N = 2 measurements. The dotted horizontal line denotes a concentration of 24 nM, which was the concentration of KBU2046 measured in the blood of mice whose metastasis were suppressed by 92% (a, b). d Prolongation of survival in BCa-bearing mice. Mice were orthotopically implanted with human breast cancer LM2-4H2N cells, the resultant primary tumors resected, and adjuvant treatment begun with KBU2046 by daily oral gavage five times per week. The survival of N = 6 mice receiving vehicle was compared to that of N = 6 mice receiving 25 mg/kg KBU2046 by the log-rank (Mantel-Cox) test