Ezetimibe (SCH 58235) is a potentcholesterolabsorption inhibitor. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potentNrf2activator.

NPC1L1, Nrf2^[1]

Ezetimibe (Eze) acts as a potent Nrf2 activator without causing cytotoxicity. Ezetimibe enhances transactivation of Nrf2, as revealed by a luciferase reporter assay. Ezetimibe also upregulates Nrf2 target genes, including GSTA1, heme oxygenase-1 (HO-1) and Nqo-1 in Hepa1c1c7 and MEF cells. Ezetimibe upregulates Nrf2 target genes in Nrf2+/+ MEF cells, whereas this induction is totally blocked in Nrf2-/- MEF cells. Taken together, Ezetimibe acts as a novel Nrf2 inducer in a ROS-independent manner^[1]. Human huh7 hepatocytes are pretreated with Ezetimibe (10 μM, 1 h) and incubated with palmitic acid (PA, 0.5 mM, 24 h) to induce hepatic steatosis. Ezetimibe treatment significantly attenuates PA-increased triglycerides (TG) levels, which is consistent with our animal study. PA treatment resulted in an approximately 20% decrease in mRNA expression of ATG5, ATG6, and ATG7, which had been increased by Ezetimibe treatment. In addition, Ezetimibe treatment significantly increased the PA-induced reduction in LC3 protein abundance^[2].

Administration of Ezetimibe (Eze) reduces the liver weights of mice fed the methionine- and choline-deficient (MCD) diet. This is consistent with the beneficial effects of Ezetimibe on hepatic steatosis. Liver histology shows pronounced multiple macrovesicular fat droplets in mice on the MCD diet, but Ezetimibe treatment markedly decreases the number and size of those droplets. Furthermore, hepatic fibrosis in mice fed the MCD diet is significantly attenuated by Ezetimibe^[1]. Blood and liver lipid levels including TG, free fatty acids (FFA), and total cholesterol (TC) are significantly decreased in Ezetimibe-treated OLETF rats. Moreover, OLETF rats show higher serum levels of glucose, insulin, HOMA-IR, TG, FFA, and TC than LETF animals, which are significantly reduced by Ezetimibe. In addition, histological analysis indicated that OLETF control rats showed larger lipid droplets in hepatocytes than age-matched LETO controls, which are attenuated by administration of Ezetimibe^[2].

409.43

Solid

C₂₄H₂₁F₂NO₃

163222-33-1

依泽替米贝

Room temperature in continental US; may vary elsewhere.

DMSO : 200 mg/mL(488.48 mM;Need ultrasonic)

H₂O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble)

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: 5 mg/mL (12.21 mM); Suspended solution; Need ultrasonic

  此方案可获得 5 mg/mL (12.21 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 50.0 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%corn oil

  Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.11 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。