Vistusertib (AZD2014) is an ATP competitivemTORinhibitor with anIC₅₀of 2.81 nM. AZD2014 inhibits bothmTORC1andmTORC2complexes.

The inhibitory effects of Vistusertib (AZD2014) are measured against isolated recombinant mTOR enzyme (IC₅₀of 2.81 nM) as well as in cellular assays measuring both mTORC1 and mTORC2 activities. In MDAMB468 cells, Vistusertib (AZD2014) decreases the phosphorylation of the mTORC1 substrate ribosomal protein S6 (Ser235/236) with a mean IC₅₀value of 210 nM and the mTORC2 substrate AKT (Ser473) with a mean IC₅₀value of 78 nM^[1].

Vistusertib (AZD2014) induces dose-dependent tumor growth inhibition in several xenograft and primary explant models. The antitumor activity of Vistusertib (AZD2014) is associated with modulation of both mTORC1 and mTORC2 substrates, consistent with its mechanism of action. The pharmacokinetics of Vistusertib (AZD2014) in mice is tested upon administration of doses between 7.5 and 15 mg/kg. A dose-dependent increase in C_maxand AUC is observed following single dose and repeat dosing of AZD2014: C_maxrange from 1 to 16 μM and AUC range from 220 to 5,042 μM·h across this dose range. The pharmacodynamic effect of Vistusertib (AZD2014) against an mTORC1 biomarker (phosphorylation of S6) and an mTORC2 biomarker (phosphorylation of AKT) is assessed in SCID mice bearing MCF7 xenografts following administration of 3.75, 7.5, and 15 mg/kg AZD2014. There is a good relationship between the drug plasma concentrations and biomarker levels (estimated p-AKT IC₅₀of 0.119 μM total, 53% SE, and estimated p-S6 IC₅₀0.392 μM, 28.8% SE)^[1].

462.54

Solid

C₂₅H₃₀N₆O₃

1009298-59-2

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 50 mg/mL(108.10 mM)

*"≥" means soluble, but saturation unknown.

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 (5.40 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.40 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 (5.40 mM); Suspended solution; Need ultrasonic and warming

  此方案可获得 2.5 mg/mL (5.40 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  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： 5% DMSO    40%PEG300   5%Tween-80   50% saline

  Solubility: 2.5 mg/mL (5.40 mM); Suspended solution; Need ultrasonic
• 4.

  请依序添加每种溶剂： 5% DMSO    95% (20%SBE-β-CDin saline)

  Solubility: 2.5 mg/mL (5.40 mM); Suspended solution; Need ultrasonic