| 名稱 | WYE-354 |
| 描述 | WYE-354(IC50=5 nM) is an effective, selective and ATP-competitive mTOR inhibitor. It blocks mTORC2/P-AKT(S473) and mTORC1/P-S6K(T389), not P-AKT(T308). The selectivity for mTOR is higher than PI3Kα (>100-fold) and PI3Kγ (>500-fold). |
| 細胞實驗 | Tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, DU145, A498, and HCT116, are plated in 96-well plates at 1000 to 3000 cells per well for 24 hours, treated with DMSO or varying concentrations of WYE-354(0–50 μM, dissolved in DMSO) for72 hours. |
| 激酶實驗 | The assays were incubated at room temperature for 2 hours. In 96-well plates (25 μL) contains 6 nM Flag-TOR(3.5) (estimated 5-10% purity), 1 μM His6-S6K and 100 μM ATP.For inhibitor versus ATP matrix competition, mTOR kinase reactions are carried out with varying concentrations of ATP (0, 25, 50 100, 200, 400 and 800 μM) in combination with varying concentrations of inhibitor.The assays are performed and detected by DELFIA employing the Euphospho-p70S6K T389 antibody. |
| 動物實驗 | Nude mice (BALB/c, nu/nu, female) bearing PC3 mM2 xenograft were intraperitoneally injected with WYE-354（50 mg/kg）dissolved in 5% ethanol, 5% polysorbate 80, 5% PEG-400. |
| 體外活性 | 在HEK293細胞中，WYE-354（0.2 μM–5 μM）有效抑制了mTORC1和mTORC2。在U87 mg和MDA361細胞中，WYE-354（0.3 μM–10 μM）顯著阻斷了mTOR信號傳導和Akt激活。在包括MDA-MB-361、MDA-MB-231、MDA-MB-468、LNCap、A498和HCT116在內(nèi)的腫瘤細胞系中，WYE-354有效抑制了增殖，IC50值范圍為0.28 μM至2.3 μM。在內(nèi)皮HUVEC細胞中，WYE-354也抑制了mTORC1和mTORC2信號傳導，IC50值從10 nM到1 μM不等，這一效果通過S6核糖體蛋白和Akt的去磷酸化得到驗證。WYE-354引起的凋亡伴隨著G1期細胞周期阻滯和caspases激活。WYE-354（10 nM–1 μM）激活了絲裂原激活蛋白激酶（MAPK）信號傳導，這可能是由于其對mTORC1的抑制作用。 |
| 體內(nèi)活性 | WYE-354 (50 mg/kg) 在PTEN-null PC3 mM2腫瘤的小鼠異種移植模型中，強效抑制mTOR信號傳導和腫瘤生長。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 92 mg/mL (185.7 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關鍵字 | inhibit | Apoptosis | WYE354 | WYE 354 | Inhibitor | WYE-354 | Autophagy | Mammalian target of Rapamycin | mTOR |
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