product name GNE-317
Description: GNE-317 is a potent and selective PI3K inhibitor with potential anticancer activity. GNE-317 targets the PI3K pathway and can cross the Blood-Brain Barrier. GNE-317 was identified as having physicochemical properties predictive of low efflux by P-gp and BCRP. Studies in transfected MDCK cells showed that GNE-317 was not a substrate of either transporter. GNE-317 markedly inhibited the PI3K pathway in mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6-hour postdose. GNE-317 was efficacious in the U87, GS2, and GBM10 orthotopic models, achieving tumor growth inhibition of 90% and 50%, and survival benefit, respectively.
References: Clin Cancer Res. 2012 Nov 15;18(22):6239-48; Drug Metab Dispos. 2014 Jul;42(7):1110-6.
414.48
Formula
C19H22N6O3S
CAS No.
1394076-92-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 47 mg/mL warming (113.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Chemical Name
5-(6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine
other peoduct :
| In Vitro | Kinase Assay:
Cell Assay: GNE-317 is not a substrate of P-gp or BCRP transporter in transfected Madin-Darby canine kidney (MDCK) cells. Binding of GNE-317 to plasma proteins exhibits a free fraction of 14.9 % in mouse plasma, and binding to brain tissues is higher, with a free fraction of 5.4%. GNE-317 shows cytostasis but no cell death to U87 cells. |
|---|---|
| In Vivo | GNE-317 (40 mg/kg, p.o.) markedly inhibits the PI3K pathway in mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6-hour postdose. GNE-317 (40 mg/kg, p.o.) is efficacious in the U87 and GS2 orthotopic models, achieving tumor growth inhibition of 90% and 50%, respectively. In the GBM10 tumor model, GNE-317 (30 mg/kg, p.o.; 40 mg/kg the first 2 weeks) extends the survival of mice from a median of 55.5 to 75 days. |
| Animal model | U87 and GS2 orthotopic tumor-bearing mice. |
| Formulation & Dosage | Dissolved in 0.5% methylcellulose/0.2%Tween 80; 40 mg/kg; Oral administration |
| References | [1] Salphati L, et al. Clin Cancer Res. 2012, 18(22):6239-6248. |
