PKI-179

PKI-179 is a potent and orally active dual PI3K/mTOR inhibitor, with IC₅₀s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC₅₀s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo^[1][2]. In Vitro: PKI-179 inhibits the cell proliferation, with IC₅₀s of 22 nM and 29 nM for MDA361 and PC3 cells, respectively^[1].
PKI-179 shows inhibitory activity against a panel of 361 other kinases, hERG and cytochrome P450 (CYP) isoforms at concentrations up to >30 μM, but does have activity for CYP2C8 (IC₅₀=3 μM)^[1]. In Vivo: PKI-179 (5-50 mg/kg; p.o. once daily for 40 days) inhibits the tumor growth and is well tolerated in nude mice bearing MDA-361 human breast cancer tumors^[1].
PKI-179 (50 mg/kg; p.o.) results in good inhibition of PI3K signaling in nude mice bearing MDA361 tumor xenografts^[1].
PKI-179 exhibits good oral bioavailability (98% in nude mouse, 46% in rat, 38% in monkey, and 61% in dog) and a high half-life (>60 min) ^[1].