GNE-317 (C007B-173499)

InformationGNE-317 GNE-317 is a potent, brain-penetrant PI3K inhibitor.TargetsPI3KIn vitroGNE-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 vivoGNE-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. Specification: 0.98 Molecular Formula: C19H22N6O3S Molecular Weight: 414.48 PubChem CID: 70676303 Isomeric SMILES: CC1=C(SC2=C1N=C(N=C2N3CCOCC3)C4=CN=C(N=C4)N)C5(COC5)OC Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/G413834-SCI_20d2ed4b9bc8ff8e1550b56ffe29238d.pdf