Biological Activity |
Wortmannin is a multi-target inhibitor. Wortmannin inhibits PI3K[1], MLCK[1], DNA-PK[2], ATM[2], ATR[2], and Polo-like kinase 3 (Plk3[3]) with IC50s of 3 nM, 200 nM, 16 nM, 150 nM, 1.8 uM and 48 nM, respectively. IC50 & Target: IC50: 3 nM (PI3K), 200 nM (MLCK)[1] IC50: 16 nM (DNA-PK), 150 nM (ATM), 1.8 uM (ATR)[2] In Vitro: Wortmannin (0-100 nM; 24-72 hours) inhibits the proliferation of K562 cells in a time- and dose-dependent manner. The IC50 values at 24 hour, 48 hour, and 72 hour are 25+/-0.10 nM, 12.5+/-0.08 nM, and 6.25+/-0.11 nM, respectively[4]. In Vivo: Wortmannin (oral gavage; daily; in Scid mice; one group of eight mice is dosed with Wortmannin 1 mg/kg for all 14 days. The second group of eight mice is dosed with Wortmannin 1.5 mg/kg for the first 5 days and the dose is decreased to 1 mg/kg for the remaining treatment period) treatment significantly slower the growth rate of murine C3H mammary tumor and human MCF-7 breast cancer xenograft. A dose of 1 mg/kg Wortmannin for 7 days decrease the tumor burdens in mice with established murine C3H mammary tumors by 54% relative to controls. Human MCF-7 breast cancer xenograft burdens are decreased by 97% relative to controls after 14 days of 1 mg/kg Wortmannin beginning 1 day after tumor implantation[5]. |