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| 10g |
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Clofibrate (Atromid-S) is a novel and potent lipid-lowering agent acting as an agonist of PPAR with EC50s of 50 μM, ∼500 μM for murine PPARα and PPARγ, and 55 μM, ∼500 μM for human PPARα and PPARγ, respectively. It has been marketed as a fibrate and is a derivative of aryloxyisobutyric acid with antihyperlipidemic activity. Ass a lipid-lowering agent, Clofibrate is used for controlling the high cholesterol and triacylglyceride level in the blood. In order to encourage the conversion of VLDL to LDL and subsequently lower the level of VLDL, it raises lipoprotein lipase activity. It also has the ability to raise HDL levels.
| Targets |
PPARα (EC50 = 50 μM); PPARγ (IC50 = 500 μM)
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|---|---|
| ln Vitro |
Clofibrate is a PPAR agonist; its E50s for murine PPARα and PPARγ are 50 μM, approximately 500 μM, and for human PPARα and PPARγ are 55 μM, approximately 500 μM, respectively[1]. In two rat hepatoma cells treated with fatty acids (FA), clofibrate (0.5, 1, 2 mM) increases the expression of FABP1. When administered early, clofibrate significantly reduces ROS levels in FA-treated cells compared to when administered later[2].
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| ln Vivo |
Clofibrate (0.5%) elevates fetal serum concentrations and hepatic expression of FGF21, returning to baseline levels upon cessation of clofibrate treatment. Offspring administered with Clofibrate exhibit markedly increased expression of thermogenic genes (Ucp1, Cidea, Ppara Ppargc1a, Cpt1b) and UCP1 protein levels in response to a high-fat diet in the inguinal fat, but not in the epididymal or retroperitoneal fat (when combined with perirenal fat)[3].
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| Cell Assay |
In MEM/EBSS medium, cells are seeded at a density of 2.5 × 104 cells/well (for WST-1, intracellular lipid droplet quantification and dichlorofluorescein (DCF) assay, 96-well plates) or 1 × 105 cells/well (for Nile Red Staining, 12-well plates) and incubated overnight for adherence. The following day, fresh medium containing the fatty acid mixture oleate:palmitate (2:1) in the presence of 3% fatty acid-free bovine serum albumin is added to the cell culture medium. Fatty acid (FA) mixtures ranging from 0.5 to 3 mM are applied to cells for 24 to 48 hours at 37°C in a humidified incubator with 95% air and 5% CO2. FABP1 levels in treated cell cultures are raised by clofibrate. After dissolving 500 μM of clofibrate in DMSO, it is added to the medium (final volume of DMSO < 0.1% v/v). Only DMSO is used to culture the control cells. One-day FA treatment, two-day FA treatment, early clofibrate intervention, and late clofibrate intervention are the four distinct cell treatments that are available[1].
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| Animal Protocol |
C57BL/6JNarl mice, both male and female, are used in breeding. We use females whose parity ranges from 1 to 5. From breeding through parturition, pregnant females are fed either an experimental (CF) or control (C) diet. The CF diet is the C diet plus 0.5% clofibrate, while the C diet is based on an AIN-93M diet with a minor modification to include 21 kcal% fat from soybean oil. The presence of a vaginal plug (defined as pregnancy day 1) indicates the date of pregnancy. Following natural childbirth on day 19.5 ± 0.5 of pregnancy, all littermates are equally cared for by their mothers, who feed them the C diet for three weeks, adjusting the litter sizes to 8–10. Then, the babies are weaned onto a standard diet that isn't purified for four weeks, and finally, they are moved to a high-fat, butter-based daily fast for five weeks. In this investigation, only male progeny are employed, and two cohorts of progeny are identified based on the dietary habits of their mothers (CF or C). A controlled 12-hour light/dark cycle, unlimited access to food and water, and a temperature maintained at 23 ± 2°C are provided for each mouse. Weekly records are kept on body weight and feed consumption[3].
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| References |
| Molecular Formula |
C12H15CLO3
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|---|---|
| Molecular Weight |
242.7
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| Exact Mass |
242.07097
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| Elemental Analysis |
C, 59.39; H, 6.23; Cl, 14.61; O, 19.78
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| CAS # |
637-07-0
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| Related CAS # |
Clofibrate;637-07-0
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| Appearance |
Colorless to light yellow liquid
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| SMILES |
CCOC(=O)C(C)(C)OC1=CC=C(C=C1)Cl
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| InChi Key |
KNHUKKLJHYUCFP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H15ClO3/c1-4-15-11(14)12(2,3)16-10-7-5-9(13)6-8-10/h5-8H,4H2,1-3H3
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| Chemical Name |
ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
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| Synonyms |
Clofibrate; Clofibrato; Ethyl clofibrate; Clofibratum; Atromid-S
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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) |
DMSO: ~7 mg/mL (~28.8 mM)
Ethanol: ~5 mg/mL (~20.6 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1203 mL | 20.6016 mL | 41.2031 mL | |
| 5 mM | 0.8241 mL | 4.1203 mL | 8.2406 mL | |
| 10 mM | 0.4120 mL | 2.0602 mL | 4.1203 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 |
| NCT00000483 | Completed | Drug: estrogen Drug: clofibrate |
Coronary Disease Heart Diseases |
National Heart, Lung, and Blood Institute (NHLBI) |
June 1981 | Not Applicable |
| NCT00000482 | Completed | Drug: estrogen Drug: clofibrate clofibrate |
Heart Diseases Coronary Disease |
National Heart, Lung, and Blood Institute (NHLBI) |
April 1965 | Phase 3 |
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