Vps34-IN-2

1523404-29-6

C18H25F3N4O3

10 mM in DMSO

PI3K/Akt/mTOR

Vps34-IN-2 is a novel, potent and selective inhibitor of Vps34 with IC₅₀s of 2 and 82 nM on the Vps34 enzymatic assay and the GFP-FYVE cellular assay, respectively. IC50 & Target: IC50: 2 nM (Vps34 on enzymatic assay), 82 nM (Vps34 on GFP-FYVE cellular assay)^[1] In Vitro: Vps34-IN-2 (Compound 31) displays IC₅₀s of 2 and 82 nM on the Vps34 enzymatic assay and the GFP-FYVE cellular assay, respectively. Vps34-IN-2 exhibits selectivity against mTOR (IC₅₀>10 uM) and class I PI3Ks (IC₅₀ values of 2.7, 4.5, 2.5, and >10 uM on PI3K alpha, beta, delta, gamma isoforms, respectively)^[1]. In Vivo: After administration by the intravenous (iv) route, Vps34-IN-2 (Compound 31) concentrations are quantifiable up to 6, 8, and 24 h (last sampling time) depending on animals. After oral administration (po), Vps34-IN-2 is rapidly absorbed with maximal plasma concentrations observed at 0.5 h and a bioavailability of 85%. Slight rebounds of concentrations are observed at 4 and 8 h after oral dosing with no obvious explanation. After iv injection of Vps34-IN-2 at 3 mg/kg, plasma clearance is found moderate (i.e., 2.3 L/h/kg), corresponding to 44% of hepatic blood flow in this species, volume of distribution at steady state is moderate, and terminal elimination half-life is short^[1].