DAPT (GSI-IX) is a potent and orally activeγ-secretaseinhibitor withIC₅₀s of 115 nM and 200 nM for totalamyloid-β(Aβ)andAβ₄₂, respectively. DAPT inhibits the activation ofNotch1signaling and induces cell differentiation. DAPT also inducesautophagyandapoptosis. DAPT has neuroprotection activity and has the potential for autoimmune and lymphoproliferative diseases, degenerative disease and cancers treatment^[1][2].

IC50: 115 nM (Aβ), 200 nM (Aβ42)^[5]

DAPT inhibits Aβ production over 90%, effects only a modest reduction in APPβ in the culture media. Although APPβ is reduced by about 30% by DAPT treatment, this effect is not concentration-dependent and is reversed by the removal of DAPT^[1].
CNE-2 cells are treated with increasing concentrations of DAPT (0, 25, 50 and 75 μM), and the γ-secretase-generated Notch 1 fragment Val1744-NICD is decreased after 48 h in a dose-dependent manner (P<0.01). The activation of γ-secretase is almost completely inhibited by DAPT at the concentration of 50 μM^[3].

DAPT is administered to PDAPP mice (100 mg/kg s.c.) and the levels of DAPT and Aβ are examined in the brain cortex. Peak DAPT levels of 490 ng/g are achieved in the brain 3 h after treatment, and levels greater than 100 ng/g (~200 nM) are sustained throughout the first 18 h. These brain concentrations of DAPT are in excess of its IC₅₀for lowering Aβ in neuronal cultures (115 nM), and results in a robust and sustains pharmacodynamic effect^[1].
DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats. Western blot analyses also show a significant decrease of Notch 1 and NF-κB expression in DAPT (0.03 mg/kg) group (P<0.05 vs. MCAO group)^[2].

432.46

Solid

C₂₃H₂₆F₂N₂O₄

208255-80-5

Room temperature in continental US; may vary elsewhere.

DMSO : 62.5 mg/mL(144.52 mM;Need ultrasonic)

Ethanol : 10 mg/mL(23.12 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： 50%PEG300   50% saline

  Solubility: 5 mg/mL (11.56 mM); Suspended solution; Need ultrasonic
• 2.

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

  Solubility: ≥ 2.5 mg/mL (5.78 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.78 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
• 3.

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

  Solubility: 2.5 mg/mL (5.78 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (5.78 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
• 4.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (5.78 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.78 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。

• 5.

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

  Solubility: ≥ 1 mg/mL (2.31 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (2.31 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 EtOH 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