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Ezetimibe

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Chemical Structure| 163222-33-1 同义名 : SCH 58235;Ezetrol;Ezetimibe, Zetia, Ezetrol,
CAS号 : 163222-33-1
货号 : A124629
分子式 : C24H21F2NO3
纯度 : 98%
分子量 : 409.425
MDL号 : MFCD00937872
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 190 mg/mL(464.07 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 5 mg/mL clear

PO 0.5% CMC-Na 32 mg/mL suspension

生物活性
描述 Ezetimibe is a potent cholesterol absorption inhibitor. Ezetimibe is a Niemann-Pick C1-like1 (NPC1L1) inhibitor, and is a potent Nrf2 activator. Ezetimibe activates Nrf2-Keap1 pathway which was dependent of autophagy adaptor protein p62, without causing cytotoxicity. Ezetimibe activates AMP-activated protein kinase (AMPK), which in turn phosphorylates p62 (p-S351) via their direct interaction. Correspondingly, Ezetimibe protected liver cells from saturated fatty acid-induced apoptotic cell death through p62-dependent Nrf2 activation[3]. 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. In addition, autophagy-related mRNA expression including ATG5, ATG6, and ATG7 and the protein level of microtubule-associated protein light chain 3 (LC3) were significantly increased in the liver in rats that received ezetimibe[4]. Ezetimibe and pitavastatin in combination induced higher PCSK9 levels than pitavastatin monotherapy or co-therapy with ezetimibe plus Xuezhikang[5]. Long-term application of ezetimibe significantly reduced the concentrations of vitamin D3-d3 in the serum and tissues of mice[6]. Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin, which was associated with lowering serum cholesterol, decreasing circulating inflammatory cytokines, and inhibiting macrophage accumulation in the lesions[7].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00101439 Hypercholesterolemia Phase 3 Completed - -
NCT00101439 - Completed - -
NCT00863265 - Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.44mL

0.49mL

0.24mL

12.21mL

2.44mL

1.22mL

24.42mL

4.88mL

2.44mL
参考文献

[1]Clader JW. The discovery of ezetimibe: a view from outside the receptor. J Med Chem. 2004 Jan 1;47(1):1-9.

[2]van Heek M, Farley C, et al. Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function. Br J Pharmacol. 2001 Sep;134(2):409-17.

[3]Lee DH, Han DH, Nam KT, Park JS, Kim SH, Lee M, Kim G, Min BS, Cha BS, Lee YS, Sung SH, Jeong H, Ji HW, Lee MJ, Lee JS, Lee HY, Chun Y, Kim J, Komatsu M, Lee YH, Bae SH. Ezetimibe, an NPC1L1 inhibitor, is a potent Nrf2 activator that protects mice from diet-induced nonalcoholic steatohepatitis. Free Radic Biol Med. 2016 Oct;99:520-532

[4]Chang E, Kim L, Park SE, Rhee EJ, Lee WY, Oh KW, Park SW, Park CY. Ezetimibe improves hepatic steatosis in relation to autophagy in obese and diabetic rats. World J Gastroenterol. 2015 Jul 7;21(25):7754-63

[5]Zhang Y, Liu J, Li S, Xu RX, Sun J, Li JJ. Impact of currently prescribed lipid-lowering drugs on plasma PCSK9 concentration: single or in combination study in rats. Lipids Health Dis. 2014 Feb 18;13:35

[6]Kiourtzidis M, Kühn J, Schutkowski A, Baur AC, Hirche F, Stangl GI. Inhibition of Niemann-Pick C1-like protein 1 by ezetimibe reduces uptake of deuterium-labeled vitamin D in mice. J Steroid Biochem Mol Biol. 2020 Mar;197:105504

[7]Tie C, Gao K, Zhang N, Zhang S, Shen J, Xie X, Wang JA. Ezetimibe Attenuates Atherosclerosis Associated with Lipid Reduction and Inflammation Inhibition. PLoS One. 2015 Nov 10;10(11):e0142430