Gedatolisib

Gedatolisib (PKI-587) is a highly potent dual inhibitor of PI3Kα, PI3Kγ, and mTOR with IC₅₀s of 0.4 nM, 5.4 nM and 1.6 nM, respectively^[1]. Gedatolisib is equally effective in both complexes of mTOR, mTORC1 and mTORC2^[2]. IC50 & Target:IC50: 0.4 nM (PI3Kα), 5.4 nM (PI3Kγ), 1.6 nM (mTOR), 6 nM (PI3Kβ), 6 nM (PI3Kδ)^[1]
mTORC1, mTORC2^[3] In Vitro: Gedatolisib (PKI-587) shows good potency in cell growth inhibition assays using MDA-361 and PC3-MM2 cell lines with IC₅₀s of 4.0 and 13.1 nM, respectively^[1].
Gedatolisib shows potent suppression of phosphorylation of PI3K/mTOR signaling pathway proteins in MDA-361 tumor cells. Gedatolisib (0.03-3 μM; 4 hours) prevents the phosphorylation of Akt at Thr 308 and induces cleaved PARP at 30 nM^[1]. In Vivo: Gedatolisib (PKI-587; administered i.v. at 20 mg/kg on days 1, 5, 9) exhibits potent antitumor efficacy against MDA-361 tumors in mice^[1].
Gedatolisib exhibits terminal elimination half-life (T_1/2 14.4 h) due to high plasma clearance (7 mL/min/kg) combined with large volumes of distribution (7.2 L/kg respectively) following i.v. administration (25 mg/kg) female nude mice^[1].