In vitro: 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.
Cell Experiment | |
---|---|
Cell lines | |
Preparation method | |
Concentrations | |
Incubation time |
Animal Experiment | |
---|---|
Animal models | U87 and GS2 orthotopic tumor-bearing mice |
Formulation | 0.5% methylcellulose/0.2%Tween 80 |
Dosages | 40 mg/kg |
Administration | p.o. |
Molecular Weight | 414.48 |
Formula | C19H22N6O3S |
CAS Number | 1394076-92-6 |
Solubility (25°C) | 47 mg/mL warmed in DMSO |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Related PI3K Products |
---|
SNV4818
SNV4818 is a potential best-in-class (best-in-class) mutation-selective PI3K-α inhibitor with excellent selectivity for the H1047X mutant and moderate selectivity for the related E545/542X mutant. |
hSMG-1 inhibitor 11j
hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC50 of 0.11 nM. |
RLY-2608
RLY-2608 is a first-in-class, orally active, selective inhibitor of PI3Ka metabolism. |
EDI048
EDI048 is an orally active Cryptosporidium PI4K inhibitor for the research of cryptosporidiosis. |
PI3Kδ-IN-13
PI3Kδ-IN-13 is a PI3Kδ inhibitor (IC50=2.6 nM). |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.