WYE-354 is an ATP-competitivemTORinhibitor with anIC₅₀of 5 nM. WYE-354 also inhibitsPI3KαandPI3KγwithIC₅₀s of 1.89 μM and 7.37 μM, respectively. WYE-354 inhibits bothmTORC1andmTORC2. WYE-354 inducesautophagyactivation in vitro^[3].

In the DELFIA measuring His6-S6K1 T389 phosphorylation, WYE-354 inhibits recombinant mTOR enzyme with an IC₅₀of 5 nM^[1]. Cell viability is analyzed by MTS assay. G-415 and TGBC-2TKB cell lines are treated with increasing concentrations of WYE-354 (0.1, 1, 5 and 10 μM) for 24, 48, and 72 hours. WYE-354 significantly reduces cell viability starting at a 1 μM concentration after a 24 hours exposure, in both studied cell lines (P<0.001). A decrease in cell viability is not observed at a dose of 100 nM, except for the TGBC-2TKB cell line after 72 hours of treatment^[2].

The effect of Rapamycin and WYE-354 on tumor growth is evaluated in xenograft GBC tumor models. 2×10⁶or 5×10⁶cells of G-415 or TGBC2TKB, respectively, are xenotransplanted into NOD-SCID mice subcutaneously. When tumors reach an average volume of 100 mm³, the mice are treated either with Rapamycin or WYE354. Rapamycin is administered i.p. at a concentration of 10 mg/kg, daily for 5 days per week for 3 weeks, while WYE-354 is administrated at a daily i.p. dose of 50 mg/kg for 5 days. Mice are sacrificed 30 days after the initiation of the treatments and an autopsy is performed that include removal of the entire tumor area. Mice treated with WYE-354 exhibit 68.6% and 52.4% reduction in average tumor size (P<0.01; P<0.01), as well as 82.9% and 45.5% (P<0.01; ns) reduction in tumor weight, respectively^[2].

495.53

Solid

C₂₄H₂₉N₇O₅

1062169-56-5

Room temperature in continental US; may vary elsewhere.

DMSO : 6.67 mg/mL(13.46 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: ≥ 0.67 mg/mL (1.35 mM); Clear solution

  此方案可获得 ≥ 0.67 mg/mL (1.35 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 6.7 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: ≥ 0.67 mg/mL (1.35 mM); Clear solution

  此方案可获得 ≥ 0.67 mg/mL (1.35 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 6.7 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: ≥ 0.67 mg/mL (1.35 mM); Clear solution

  此方案可获得 ≥ 0.67 mg/mL (1.35 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 6.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。