Figure 5: Inhibition of in vivo CRPC tumor growth by KCI807.

(a) Tumor xenografts of 22Rv1 cells were implanted sc into male SCID mice (5 mice per group) in both flanks. Drugs were administered beginning on Day 3 of implantation. The treatments include 250mg/Kg of KCI807 injected intraperitoneally, on alternate days or vehicle control. In parallel, groups of 5 mice similarly administered KCI807 were sacrificed precisely 6h after the last injection of KCI807 on Day 3, Day 11 and Day 19 for analysis of plasma levels of unmetabolized KCI807. For comparison of anti-tumor efficacy, enzalutamide was administered to a separate group of mice following the standard regimen of daily oral administration of 50mg/kg. Tumor volume curves and plasma concentration-time profiles are plotted as median and an interval of semi-interquartile range on the basis of their raw values. The p-values were obtained using a linear mixed-effects model after a log-transformation of the raw values. (b) PDX-PR011 tumor xenografts were implanted sc into male SCID mice (5 mice per group) in both flanks. The vehicle control and KCI807 were administered as described for Panel a, with the exception that treatment was begun on Day 1 after tumor implantation. Tumor volumes were monitored as described above.