CZ415 is a potent and highly selective mTOR inhibitor with a pIC₅₀ of 8.07. CZ415 inhibits mTORC1 and mTORC2 protein complex.

Inhibition of phosphorylation for both downstream targets results in 14.5 nM IC₅₀ for pS6RP and 14.8 nM for pAKT. The immunosuppressive effect of CZ415 is measured by detecting secreted IFNγ after 18 hours in stimulated human whole blood and the resulting IC₅₀ is 226 nM. As a predictor for cardiotoxicity, the activity of CZ415 against the human cardiac ion channel hERG is assessed in a whole-cell patch-clamp assay in HEK293 cells resulting in an IC₅₀ of 48 μM^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

CZ415 is a highly selective mTOR inhibitor showing in vivo efficacy in a collagen induced arthritis (CIA) model. For full characterization of CZ415 and to enable improved dose predictions, the pharmacokinetic (PK) profile is assessed in rat. PK and oral bioavailability are determined after of 1 mg/kg intravenous (iv) bolus and 3 mg/kg oral (po) administration. The observed plasma clearance, corresponding to 45% liver blood flow, suggests that sufficient levels of free compound are circulating in the animal over time. The oral uptake is rapid with a T_maxmax of 0.5 h and bioavailability F = 44% indicates very good absorption from the gut^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

459.56

C₂₂H₂₉N₅O₄S

1429639-50-8

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 100 mg/mL (217.60 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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

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 (5.44 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.44 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-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.44 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.44 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 μL 20% 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 (5.44 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.44 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。

• [1]. Cansfield AD, et al. CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model. ACS Med Chem Lett. 2016 Jun 10;7(8):768-73.

Mice^[1]
To determine the effects of CZ415 on its pharmacological target, dose-dependent changes in phosphorylation levels of S6 Ribosomal Protein and Akt – both downstream targets of mTOR are assessed. CZ415 is administered orally at 1, 3 and 10 mg/kg to mice 1 h before anti-CD3 stimulus. 15 min after stimulation, spleens are dissected and analyzed for pS6RP and pAKT levels. A dose related significant inhibition of phosphorylation of both S6RP and Akt are observed after compound administration. In particular, 1 and 3 mg/kg CZ415 could fully inhibit S6RP phosphorylation induced by anti-CD3 stimulation and 10 mg/kg additionally decreased the constitutive phosphorylation levels as measured in the control group.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Cansfield AD, et al. CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model. ACS Med Chem Lett. 2016 Jun 10;7(8):768-73.