| Description | Vps34-IN-2 is a potent and selective Vps34 inhibitor (IC50s: 2 and 82 nM on the Vps34 enzymatic assay and the GFP-FYVE cellular assay, respectively). |
| In vitro | Vps34-IN-2 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 with IC50 more than 10 μM and class I PI3Ks with IC50 values of 2.7, 4.5, 2.5, and >10 μM on PI3K α, β, δ, γ isoforms, respectively. |
| In vivo | 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. |
| Target activity | VPS34:2 nM |
| molecular weight | 402.41 |
| Molecular formula | C18H25F3N4O3 |
| CAS | 1523404-29-6 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: 50 mg/mL (124.25 mM), Sonication is recommended. |
| References | 1. Pasquier B, et al. Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors. J Med Chem. 2015 Jan 8;58(1):376-400. |