GNE-490 reduces pAkt, pS6RP, and tumor growth in HM-7 colorectal cancer and NCI-PC3 prostate cancer xenograft models. (A and B) HM-7 tumor-bearing mice (n = 3) were treated with a single oral dose of GDC-0980 (10 mg/kg) or GNE-490 (30 mg/kg) or i.p. dose of B20.4.1.1 (10 mg/kg) and harvested 1 hour post-dose to measure the levels of pAkt (S473) normalized to tAkt (A) or pS6RP (S235/236) normalized to tS6RP (B) using Meso Scale Discovery assays (mean ± SEM). (C and D) NCI-PC3 tumor-bearing mice (n = 4) were treated with a single dose of MCT vehicle (control), GDC-0980 (10 mg/kg), or GNE-490 (30 mg/kg), and tumors were harvested 1 hour post-dose to measure the levels of pAkt (S473) normalized to tAkt (C) or pS6RP (S235/236) normalized to tS6RP (D). (E and F) Mean tumor volumes from HM-7 (E) and NCI-PC3 (F) tumor-bearing mice treated daily and p.o. with MCT vehicle (control), GDC-0980 (10 mg/kg), or GNE-490 (30 mg/kg) for 7 days. B20.4.1.1 (10 mg/kg) was administered i.p. on days 1 and 7. Comparisons to control were performed using Dunnett's method; comparisons between treatment groups were performed using unpaired t test assuming unequal variances: *P < .05, **P < .01, ***P < .001.