Therapeutic agents

The AR inhibitor MDV3100, enzalutamide, was synthesized by the MSKCC chemistry core. MDV3100 was used in our studies in vitro at a concentration of 10 mmol/L and in vivo with a dose of 10 mg/kg/day²⁹. The PI3K p110α-selective inhibitor BYL719 was purchased from LC Laboratories (cat# A-4477). BYL719 was dissolved in 0.5% methyl cellulose and dosed at 25 mg/kg daily P.O. The PI3K p110β-selective inhibitor AZD8186 was kindly provided by Laboratory of Neal Rosen and purchased from SelleckChem (cat# S7694). AZD8186 was dissolved in 0.5% HPMC + 0.1% Tween80 and dosed at 75 mg/kg b.i.d P.O. Pan-PI3K inhibitor BKM120 was purchased from SelleckChem (cat# S2247). BKM120 was dissolved in 0.5% methyl cellulose and dosed at 50 mg/kg daily P.O. IGF1R/INSR inhibitor linsitinib was purchased from LC Laboratory (cat# L-5814). Linsitinib was dissolved in 25 mM Tartaric Acid and dosed at 40 mg/kg daily P.O. AKT inhibitor ipatasertib was provided by Genentech under an MTA and was dissolved in 0.5% Methylcellulose and 0.2% Tween-80 for in vivo study.