Torkinib (PP 242) is a selective and ATP-competitivemTORinhibitor with anIC₅₀of 8 nM^[1]. PP242 inhibits bothmTORC1andmTORC2withIC₅₀s of 30 nM and 58 nM, respectively^[2].

Torkinib (PP 242) potently inhibits mTOR (IC₅₀=8 nM) but is much less active against other PI3K family members. Testing of Torkinib (PP 242) against 219 protein kinases reveals remarkable selectivity relative to the protein kinome: at a concentration 100-fold above its IC₅₀for mTOR, Torkinib (PP 242) inhibits only one kinase by more than 90% (Ret) and only three by more than 75% (PKCα, PKCβII and JAK2^V617F)^[1]. Torkinib (PP 242) has a dose-dependent effect on proliferation and at higher doses is much more effective than Rapamycin at blocking cell proliferation. The ability of Torkinib (PP 242) to block cell proliferation more efficiently than Rapamycin could be a result of its ability to inhibit mTORC1 and mTORC2, because Rapamycin can only inhibit mTORC1. In SIN1^-/-mouse embryonic fibroblasts (MEFs), Rapamycin is also less effective at blocking cell proliferation than Torkinib. That Torkinib (PP 242) and Rapamycin exhibit very different anti-proliferative effects in SIN1^-/-MEFs suggests that the two compounds differentially affect mTORC1^[2].

In fat and liver, Torkinib (PP 242) is able to completely inhibit the phosphorylation of Akt at S473 and T308, consistent with its effect on these phosphorylation sites observed in cell culture. Surprisingly, Torkinib (PP 242) is only partially able to inhibit the phosphorylation of Akt in skeletal muscle and is more effective at inhibiting the phosphorylation of T308 than S473, despite it's ability to fully inhibit the phosphorylation of 4EBP1 and S6. These results will be confirmed by in vivo dose-response experiments, but, consistent with the partial effect of Torkinib (PP 242) on pAkt in skeletal muscle, a muscle-specific knockout of the integral mTORC2 component rictor resulted in only a partial loss of Akt phosphorylation at S473. These results suggest that a kinase other than mTOR, such as DNA-PK, may contribute to phosphorylation of Akt in muscle^[2].

308.34

Solid

C₁₆H₁₆N₆O

1092351-67-1

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL(162.16 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% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (8.11 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.11 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (8.11 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.11 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (8.11 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.11 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。