Wortmannin

Wortmannin (SL-2052; KY-12420) is a potent, selective and irreversible PI3K inhibitor with an IC₅₀ of 3 nM. Wortmannin also blocks autophagy formation, and potently inhibits Polo-like kinase 1 (PlK1) and Plk3 with IC₅₀s of 5.8 and 48 nM, respectively^[1][2][3]. IC50 & Target: IC50: 3 nM (PI3K), 200 nM (MLCK)^[1]
IC50: 16 nM (DNA-PK), 150 nM (ATM), 1.8 μM (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]. Wortmannin prevents nuclear entry of YAP^[6]. 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].