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WYE-354 is a potent and ATP competitive inhibitor of mTOR (IC50 = 5 nM), with significant selectivity over PI3K isofoms (>100-fold). WYE-354 is equally potent against mTORC1 and mTORC2 activities in HEK293 immune complex kinase assays using S6K and Akt as the respective substrate (IC50 <200 nM) and effectively blocks cellular phosphorylation of S6K on T389 and Akt on S473 both in cultures and in a murine xenograft model, resulting in a significant suppression of PC3MM2-derived tumor growth (by 86% on day 7; 50 mg/kg, i.p twice per day) in vivo.
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Source | Oncotarget (2015). Figure 1. WYE-354 |
| Method | MTS assay | |
| Cell Lines | Western blot analysis | |
| Concentrations | 1 μM | |
| Incubation Time | 24, 48, and 72 h | |
| Results | WYE-354 significantly reduced cell viability starting at a 1 μM concentration after a 24 hours exposure, in both studied cell lines |
| Cell Experiment | |
|---|---|
| Cell lines | Cell lines of Rat1, HEK293, MDA-MB-361, MDA-MB-468, MDA-MB-231, LNCap, DU145, U87MG, A498, HCT116, and HT29 |
| Preparation method | Tumor cell growth assays. |
| Concentrations | 0~100 μ M |
| Incubation time | 3 days |
| Animal Experiment | |
|---|---|
| Animal models | PC3MM2 tumors xenograft in BALB/c nu/nu female mice |
| Formulation | formulated in 5% ethanol, 5% polysorbate 80, 5% polyethylene glycol-400 |
| Dosages | a single i.p. injection with 50 mg/kg |
| Administration | i.p. |
| Molecular Weight | 495.5 |
| Formula | C24H29N7O5 |
| CAS Number | 1062169-56-5 |
| Solubility (25°C) | DMSO 30 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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