Torin 2 is anmTORinhibitor withEC₅₀of 0.25 nM for inhibiting cellularmTORactivity, and exhibits 800-fold selectivity overPI3K(EC₅₀: 200 nM). Torin 2 also inhibitsDNA-PKwith anIC₅₀of 0.5 nM in the cell free assay. Torin 2 can suppress bothmTORC1andmTORC2.

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 EC₅₀for inhibiting mTOR in cells while maintaining 800-fold cellular selectivity relative to inhibition of PI3K and most other protein kinases^[1]. Torin 2 (Torin2) exhibits potent biochemical and cellular activity against PIKK family kinases including ATM (EC₅₀28 nM), ATR (EC₅₀35 nM) and DNA-PK (EC₅₀118 nM). Torin 2 potently inhibits T308 of Akt, a direct substrate of PDK1 and an indirect substrate of PI3Ks, with an EC₅₀of less than 10 nM^[2]. Torin-2 can suppress both mTORC1 and mTORC2^[4].

Torin 2 (Torin2) 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^[1]. Torin 2 (Torin2) 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^[2]. Treatment with Torin 2 (Torin2) 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^[3].

432.40

Solid

C₂₄H₁₅F₃N₄O

1223001-51-1

Room temperature in continental US; may vary elsewhere.

DMSO : 15.62 mg/mL(36.12 mM;Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% 1-Methyl-2-pyrrolidinone    90%PEG300

  Solubility: ≥ 2 mg/mL (4.63 mM); Clear solution
• 2.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 1.56 mg/mL (3.61 mM); Clear solution

  此方案可获得 ≥ 1.56 mg/mL (3.61 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 15.6 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液