Size | Price | Stock | Qty |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Other Sizes |
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Purity: ≥98%
Ezetimibe (also known as SCH-58235) is a potent and selective inhibitor of cholesterol absorption in the gut used to lower cholesterol levels. It functions by directly interfering with Niemann-Pick C1-like 1 (NPC1L1), preventing it from integrating into clathrin-coated vesicles. It is possible to absorb cholesterol through clathrin/AP2-mediated endocytosis thanks to the polytopic transmembrane protein NPC1L1. Ezetimibe inhibits cholesterol transfer across membranes by binding to NPC1L1 and preventing this protein's endocytosis. Clinical trials have shown that ezetimibe can reduce plasma cholesterol levels.
Targets |
NPC1L1; Nrf2
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ln Vitro |
Ezetimibe results in a small but significant increase in HDL cholesterol as well as a significant decrease in triglycerides, LDL cholesterol, and total cholesterol. [1] In Caco-2 cells, ezetimibe decreases cholesterol transport by 31% but does not affect retinol transport. As determined by real-time PCR analysis in Caco-2 cells, ezetimibe significantly reduces the mRNA expression of the nuclear and surface receptors retinoid acid receptor (RAR)gamma, sterol-regulatory element binding proteins (SREBP)-1 and -2, and liver X receptor (LXR)beta. [2]
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ln Vivo |
Ezetimibe lowers plasma cholesterol levels in mice on a western, low-fat, and cholesterol-free diet from 964 to 374 mg/dL, 726 to 231 mg/dL, and 516 to 178 mg/dL, respectively. Ezetimibe reduces the surface area of aortic atherosclerotic lesions from 20.2% to 4.1% in the group eating a western diet and from 24.1% to 7.0% in the mice eating a low-fat cholesterol diet. Ezetimibe decreases the cross-sectional area of carotid artery atherosclerotic lesions by 97% in the western and low-fat cholesterol groups and by 91% in mice lacking in cholesterol. Under western, low-fat, and cholesterol-free dietary conditions, ezetimibe inhibits cholesterol absorption, lowers plasma cholesterol, raises high density lipoprotein levels, and slows the development of atherosclerosis in apoE-/- mice.[3] Ezetimibe significantly lowers plasma cholesterol in preclinical animal models of hypercholesterolemia by potently inhibiting the transport of cholesterol across the intestinal wall. The rat model has shown that ezetimibe maintains bile flow while eliminating exocrine pancreatic function from the intestine. [4] With an ED(50) of 0.04 mg/kg, ezetimibe lowers plasma cholesterol and hepatic cholesterol buildup in hamsters receiving cholesterol-filled diets. [5]
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Enzyme Assay |
Escherichia coli is used to produce GST-p62, and 0.5 μg of the purified protein is used in an in vitro AMPK phosphorylation assay. A non-radioisotope method using S-ATP is used to determine the phosphorylation of the p62 protein by AMPK. AMPK complex is immuno-purified from HEK293 cells, and then Flag-AMPKβ1 and HA-AMPKγ1 are transfected into either myc-AMPKα1 wild-type (WT) or myc-AMPKα1 kinase-dead mutant (KD, D157A) cells. The reaction mixture contains 20 mM HEPES, pH 7.4, 1 mM EGTA, 0.4 mM EDTA, 5 mM MgCl2, 0.05 mM DTT, 0.5 μg GST-p62, 0.2 mM AMP, and 1 mM ATPS. AMPK complex is then added to the mixture. 30 minutes are spent conducting the reaction at 37°C, followed by the addition of 20 mM EDTA to end it. The reaction product is alkylated with 2.5 mM PNBM for 2 hours at room temperature in order to detect p62 protein that has been γS-labeled with an S-atom [1] before being analyzed by western blotting with an anti-thiophosphate antibody.
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Cell Assay |
Huh7 human hepatocytes are cultured at 37°C in a 95% air/5% CO2 environment using high glucose DMEM containing 10% FBS, 100 units/mL penicillin, and 100 g/mL streptomycin. Ezetimibe (10 μM, 1 h) and palmitic acid (0.5 mM, 24 h) are administered to hepatocytes with or without treatment[2].
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Animal Protocol |
Mice: We use male C57BL/6J mice that are ten weeks old. The three groups—normal chow diet, MCD diet with a vehicle treatment, or MCD diet with ezetimibe treatment—each containing 7–10 mice, are randomly chosen for the animals. The temperature was kept at 23±2°C, the humidity at 60%±10%, and there were 12-hour cycles of light and darkness for the mice. Ezetimibe 10 mg/kg is administered once daily by oral gavage to the MCD diet group for a period of four weeks. The same quantity of phosphate buffered saline was given orally to the chow and MCD diet with vehicle groups for a period of four weeks. Over the course of the therapy, weight is assessed once per week. The mice are sedated and killed after four weeks, and blood is extracted through a heart puncture. After being harvested, tissues are either fixed in formalin and then embedded in paraffin, or they are instantly frozen in liquid nitrogen and kept at -70°C.
Rats: The experiments are carried out in a particular pathogen-free facility with a 12 h light/dark cycle, using male OLETF (n=11) and age-matched LETO (n=3) rats. The OLETF rat is a model that depicts late-onset hyperglycemia and displays a chronic disease course, mild obesity, and clinical onset of diabetes mellitus. Animals have unrestricted access to food and water. Rats are randomized at 12 weeks of age and given either PBS or Ezetimibe (10 mg/kg per day) by stomach gavage for 20 weeks. The rats are fasted for the duration of the study, and then intraperitoneal Zoletil/Rompun is administered to put them to sleep. The liver is dissected, its tissues are immediately frozen in liquid nitrogen, and it is then stored at -80°C for later analysis after blood is drawn from the abdominal aorta. |
References |
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Molecular Formula |
C24H21F2NO3
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Molecular Weight |
409.4
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Exact Mass |
409.15
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Elemental Analysis |
C, 70.41; H, 5.17; F, 9.28; N, 3.42; O, 11.72
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CAS # |
163222-33-1
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Related CAS # |
Ezetimibe;163222-33-1
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Appearance |
Solid powder
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SMILES |
C1=CC(=CC=C1[C@@H]2[C@H](C(=O)N2C3=CC=C(C=C3)F)CC[C@@H](C4=CC=C(C=C4)F)O)O
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InChi Key |
OLNTVTPDXPETLC-XPWALMASSA-N
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InChi Code |
InChI=1S/C24H21F2NO3/c25-17-5-1-15(2-6-17)22(29)14-13-21-23(16-3-11-20(28)12-4-16)27(24(21)30)19-9-7-18(26)8-10-19/h1-12,21-23,28-29H,13-14H2/t21-,22+,23-/m1/s1
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Chemical Name |
(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one
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Synonyms |
SCH-58235; SCH 58235; SCH-58235; SCH58235; trade names: Zetia, Ezetrol
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4426 mL | 12.2130 mL | 24.4260 mL | |
5 mM | 0.4885 mL | 2.4426 mL | 4.8852 mL | |
10 mM | 0.2443 mL | 1.2213 mL | 2.4426 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00033345 | Active Recruiting |
Drug: Ezetimibe 10mg Drug: Placebo |
Diabetes Mellitus, Type 2 Diabetic Kidney Disease |
Steno Diabetes Center Copenhagen |
October 1, 2020 | Phase 3 |
NCT03355027 | Active Recruiting |
Drug: Simvastatin 80mg Drug: Rosuvastatin 40Mg Tablet |
Atherosclerosis Cardiovascular Diseases |
Cambridge University Hospitals NHS Foundation Trust |
November 30, 2017 | Not Applicable |
NCT04701242 | Recruiting | Drug: Ezetimibe 10mg | Dyslipidemias Acute Myocardial Infarction |
Cairo University | March 24, 2021 | Not Applicable |
NCT05763875 | Recruiting | Drug: Inclisiran Drug: Ezetimibe |
Hypercholesterolemia | Novartis Pharmaceuticals | March 15, 2023 | Phase 3 |
NCT05974345 | Not yet recruiting | Drug: Placebo Drug: Ezetimibe |
Atherosclerotic Cardiovascular Disease |
Novartis Pharmaceuticals | October 17, 2023 |
Ezetimibe improves hepatic steatosis in OLETF rats. World J Gastroenterol . 2015 Jul 7;21(25):7754-63. td> |
Ezetimibe increases autophagy makers in OLETF liver tissue. World J Gastroenterol . 2015 Jul 7;21(25):7754-63. td> |
Ezetimibe treatment attenuates triglycerides accumulation and induces autophagy in hepatocytes. World J Gastroenterol . 2015 Jul 7;21(25):7754-63. td> |
Ezetimibe increases autophagosome formation and autophagic flux in hepatocytes. World J Gastroenterol . 2015 Jul 7;21(25):7754-63. td> |