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WAY-600 is a selective single digit nanomolar ATP-competitive mTOR inhibitor with an IC50 of about 9 nM. It has significant selectivity for these enzymes over phosphatidylinositol 3-kinase (PI3K) isofoms (>100-fold). With the 11% suppression by rapamycin, WAY-600 treated HEK293 cells indicated a 50% inhibition of polysomes. And WAY-600 blocked mTORC2-dependent phosphorylation of AKT in vitro and in vivo acutely. Without significant inhibition of P-AKT(T308), WAY-600 inhibited the mTORC1 substrate P-S6K(T389) and mTORC2 substrate P-AKT(S473) at submicromolar concentrations in various cancer cells.
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Source | Biochem Biophys Res Commun (2016). Figure 1.WAY-600 |
| Method | MTT viability | |
| Cell Lines | HCC cell | |
| Concentrations | 10`1000 nM | |
| Incubation Time | 48 h | |
| Results | Results in Fig. 1A showed thatWAY-600, at 10e1000 nM, significantly decreased MTT viability OD of HepG2 cells. |
| Cell Experiment | |
|---|---|
| Cell lines | MDA361 and U87MG cells |
| Preparation method | Cell lines of Rat1, HEK293, MDA-MB-361, MDA-MB-468, MDA-MB-231, LNCap, DU145, U87MG, A498, HCT116, and HT29 were obtained from the American Type Culture Collection. PC3MM2 was obtained from Dr. Carolyn Discafani (Wyeth Discovery Oncology). All cells were cultured using standard cell culture methods. For tumor cell growth assays, cells were plated in 96-well culture plates at 1000 to 3000 cells per well for 24 h, treated with DMSO or various doses of mTOR inhibitors. Viable cell densities were determined three days later by MTS assay employing an assay kit (CellTiter 96® AQueous, Cat # G5421, Promega) following the kit assay protocol. The effect of each treatment was calculated as percent of control growth relative to the DMSO-treated cells grown in the same culture plate. Inhibitor dose response curves were plotted for determination of IC50 values. |
| Concentrations | 0.01~100 μM |
| Incubation time | 3 days |
| Animal Experiment | |
|---|---|
| Animal models | PC3MM2 tumors xenograft model in BALB/c nu/nu female mice |
| Formulation | 5% ethanol, 5% polysorbate 80, 5% polyethylene glycol-400 |
| Dosages | 50mg/kg on days 0 to 4 once daily or twice daily |
| Administration | i.p. |
| Molecular Weight | 494.59 |
| Formula | C28H30N8O |
| CAS Number | 1062159-35-6 |
| Solubility (25°C) | DMSO ≥ 21 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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