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GNE-493 is a potent, selective and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitor for the treatment of cancer. The PI3K/AKT/mTOR pathway has been shown to play an important role in cancer. GNE-493 is highly selective, demonstrate knock down of pathway markers in vivo, and is efficacious in xenograft models where the PI3K pathway is deregulated.
| Cell Experiment | |
|---|---|
| Cell lines | PC3 and MCF7.1 cells |
| Preparation method | Antiproliferative cellular assays were conducted using PC3 and MCF7.1 human tumor cell lines provided by the ATCC or Genentech Research laboratories, respectively. MCF7.1 is an in vivo selected line developed at Genentech and originally derived from the parental human MCF7 breast cancer cell line (ATCC, Manassas, VA). Cell lines were cultured in RPMI supplemented with 10% fetal bovine serum, 100 units/mL penicillin, and 100 μg/mL streptomycin, 10 mM HEPES, and 2 mM glutamine at 37 C under 5% CO2. MCF7.1 cells or PC3 cells were seeded in 384-well plates in media at 1000 cells/well or 3000 cells/well, respectively, and incubated overnight prior to the addition of compounds to a final DMSO concentration of 0.5% v/v. MCF7.1 cells and PC3 cells were incubated for 3 and 4 days, respectively, prior to the addition of CellTiter-Glo reagent (Promega) and reading of luminescence using an Analyst plate reader. |
| Concentrations | 0~10 μM |
| Incubation time | 3 and 4 days |
| Animal Experiment | |
|---|---|
| Animal models | Nu/nu(nude) female mice bearing PC3 prostate cancer xenografts |
| Formulation | 0.5% methylcellulose/0.2% Tween-80 |
| Dosages | 10mg/kg daily for 14 days |
| Administration | orally |
| Molecular Weight | 372.44 |
| Formula | C17H20N6O2S |
| CAS Number | 1033735-94-2 |
| Solubility (25°C) | DMSO ≥ 35 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related PI3K Products |
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AS-605240 is a potent and selective inhibitor of PI 3-kinase γ (PI3Kγ) with an IC50 of 8 nM. |
| BEZ235
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| BKM120 (Buparlisib)
BKM120 (NVP-BKM120) is a potent and highly specific oral pan-class I PI3K inhibitor. |
| GDC-0941 (Pictilisib)
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| AS-252424
AS-252424 is a furan-2-ylmethylene thiazolidinedione as a selective ATP-competitive PI3Kγ inhibitor with IC50 with 33 nM. |
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