| 名稱 | Torin 2 |
| 描述 | Torin 2(IC50=0.25 nM), a specific and effective mTOR inhibitor, is the 800-fold greater specific activity for mTOR than PI3K and improves pharmacokinetic properties. The EC50 of Torin 2 for ATM/ATR/DNA-PK inhibition is 28 nM/35 nM/118 nM, respectively. |
| 細胞實驗 | For viability, MZ-CRC-1 and TT cells are seeded in quadruplicate in 96-well plates (1.0×104 cells per well) in culture media with 2.5% and 4% FBS, respectively. After 24 hours, cells are treated with Torin 2. At the indicated time point, cells are incubated for 3 hours with 10 μL of CellTiter96 AQueous One solution in 100 μL of culture media and absorbance is measured at 490 nm.(Only for Reference) |
| 激酶實驗 | mTOR and PI3K Cellular Assays: Cellular IC50 values for mTOR are determined using p53?/? MEFs. Cells are treated with vehicle or increasing concentrations of Torin 2 for 1 h and then lyse. Phosphorylation of S6K1 Thr-389 is monitored by immunoblotting using a phospho-specific antibody. Meanwhile, cellular IC50 values for PI3Ka are determined based on phosphorylation of Akt Thr-308 in p53?/?/mLST8?/? MEFs or human PC3 cells expressing the S473D mutant of Akt1. |
| 體外活性 | 在Th-MYCN 小鼠體內(nèi),Torin 2（20 mg/kg）消除MYCN腫瘤,減少MYCN蛋白質(zhì)水平,并誘導(dǎo)細胞凋亡.在小鼠肝微粒體穩(wěn)定性試驗中,Torin 2表現(xiàn)出>95%的藥效學(xué)響應(yīng),半衰期為11.7分鐘.在雄性Swiss albino小鼠中,靜脈內(nèi)或口服Torin 2后,體內(nèi)表現(xiàn)出最好的生物利用度為51%,半衰期為0.72小時,和低清除率是19.6 mL/min/kg. |
| 體內(nèi)活性 | 在MZ-CRC-1和TT細胞中, Torin 2（< 50 nM）引起細胞的的活性明顯減少,Torin 2（100 nM）使細胞的遷移明顯減少。Torin 2抑制mTORC1,因此通過促進其核轉(zhuǎn)運激活TFEB,EC50為1.666 mM。Torin 2與PI3Kγ具有相同的結(jié)合模式,V882作為鉸鏈結(jié)合點,在內(nèi)部疏水袋Y867,D841 和D964再提供三個作用于氨基比林側(cè)鏈的氫鍵,類似于mTOR的Y2225,D2195 和D2357。 |
| 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 : 1 mg/ml, Sonication is recommended.
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| 關(guān)鍵字 | DNA-dependent protein kinase | mTOR | Autophagy | Torin-2 | inhibit | Mammalian target of Rapamycin | DNA-PK | Torin2 | Inhibitor | Torin 2 | Apoptosis |
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