1251156-08-7

To assess the pharmacodynamic effects of XL388 (Compound 28) on the mTOR pathway signaling, athymic nude mice bearing PC-3 prostate tumors are dosed orally at 100 mg/kg of XL388. Rapamycin is also administered intraperitoneally at 5 mg/kg as a reference. Plasma and tumor samples are collected at 1, 4, 8, 16, 24, and 32 h for XL388 and at 4 h for Rapamycin after dosing and homogenized with buffer. Tumor lysates from each animal (n=5) are then pooled for each group and analyzed by immunoblot for levels of phosphorylated p70S6K, S6, 4E-BP1, and AKT. XL388 has moderate terminal elimination half-life (t_1/2=1.35 h, 0.45 h, 6.11 h and 0.86 h for mouse (10 mg/kg, iv), rat (3 mg/kg, iv), dog (3 mg/kg, iv), monkey (3 mg/kg, iv))^[1].