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Torin 2

CAS No. : 1223001-51-1

MCE 国际站：Torin 2

产品活性：Torin 2 是一种 mTOR 抑制剂，抑制细胞内 mTOR 活性，EC₅₀ 为 0.25 nM，比作用于 PI3K (EC₅₀: 200 nM) 选择性高 800 倍。体外酶实验中，Torin 2 还抑制 DNA-PK，IC₅₀ 为 0.5 nM。Torin 2 抑制 mTORC1 和 mTORC2。

研究领域：PI3K/Akt/mTOR  |  Cell Cycle/DNA Damage  |  Autophagy  |  Apoptosis

作用靶点：mTOR  |  DNA-PK  |  Autophagy  |  Apoptosis

In Vitro: Torin 2 is subject to further profiling against a panel of lipid kinases with IC₅₀s of 2.81 nM, 0.5 nM, 5.67 nM, 8.58 nM, 18.3 nM, 24.5 nM and 28.1 nM for mTOR, DNA-pK, p110γ, hVPS34, PI4Kβ, PI3K-C2β and PI3K-C2α, respectively. Torin 2 (Torin2) possesses a 250 pM EC₅₀ for inhibiting mTOR in cells while maintaining 800-fold cellular selectivity relative to inhibition of PI3K and most other protein kinases. Torin 2 (Torin2) exhibits potent biochemical and cellular activity against PIKK family kinases including ATM (EC₅₀ 28 nM), ATR (EC₅₀ 35 nM) and DNA-PK (EC₅₀ 118 nM). Torin 2 potently inhibits T308 of Akt, a direct substrate of PDK1 and an indirect substrate of PI3Ks, with an EC₅₀ of less than 10 nM. Torin-2 can suppress both?mTORC1 and mTORC2.

In Vivo: Torin 2 exhibits good bioavailability and exposure and can maintain strong inhibition of mTOR activity in lung and liver to at least six hours after a single dose of 20 mg/kg. Torin 2 is easier to produce on scale and exhibits improved pharmacokinetic properties which should enable it use in vivo experiments. Torin 2 strongly suppresses pS6K(T389) and p4EBP1(T37/46) and partly suppresses pAkt(T308). Treatment of mice with AZD6244 at 25 mg/kg results in a profound inhibition of pERK. Combined administration of Torin 2 (40 mg/kg) and AZD6244 (25 mg/kg) demonstrates strong inhibition of all pharmacodynamics markers. Treatment with Torin 2 and Rapamycin induces IL-6 secretion by astrocytes and may contribute to the reduction of mechanical hypersensitivity after SCI. Torin1 and Torin 2 treatment increases IL-6 mRNA, suggesting that the PI3K-mTOR pathway is a negative regulator of IL-6 expression in astrocytes. Importantly, Torin 2 treatment does not show any cell toxicity, as no signs of cell death are observed by TUNEL assay or by detection of cleaved-caspase 3 by western blotting.

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