| Size | Price | Stock | Qty |
|---|---|---|---|
| 10g |
|
||
| 25g | |||
| Other Sizes |
| Targets |
Clofibric acid targets PPARα, a nuclear receptor that regulates the expression of genes involved in lipid metabolism. It is a PPARα agonist with an EC50 of 50 µM in a transactivation assay. By activating PPARα, clofibric acid induces up-regulation of genes involved in peroxisome proliferation and lipid metabolism, as well as down-regulation of genes involved in apoptosis in rodent hepatocytes.
|
|---|---|
| ln Vitro |
Clofibric acid increases CYP4A6 gene expression in RK13 cells transfected with PPAR-G with EC50 of 80 μM. Clofibric acid (1 mM) treatment for 4 days induces 500-fold increase of P450 4Al RNA and 280-fold increase of acyl-CoA oxidase and P450 2Bl RNA in hepatocytes, relative to control cultures. Clofibric acid (250 μM) induces up-regulation of genes involved in peroxisome proliferation and in cell proliferation as well as down-regulation of genes involved in apoptosis in hepatocytes of rodent. Clofibric acid treatment is able to cause up-regulation of L-fatty acid binding protein (L-FABP) gene in hepatocytes of both rodent and human origin. Clofibric acid also up-regulates genes expression of the cytosolic, microsomal, and mitochondrial pathways involved in fatty acid transport and metabolism in both rodent and human hepatocyte cultures, and increases genes level of the peroxisomal pathway of lipid metabolism in rodents. An up-regulation of hepatocyte nuclear factor 1α (HNF 1α) by Clofibric acid is observed in human hepatocyte cultures. Clofibric acid also dose-dependently inhibits cell proliferation of cultured OVCAR-3 and DISS cells derived from human ovarian cancer. Clofibric acid treatment increases the expression of carbonyl reductase, which promotes the conversion of prostaglandin E2 (PGE2) to PGF 2α.
In vitro, Clofibric acid induces up-regulation of genes involved in peroxisome proliferation and in cell proliferation as well as down-regulation of genes involved in apoptosis in hepatocytes of rodent. It causes up-regulation of L-fatty acid binding protein (L-FABP) gene in hepatocytes of both rodent and human origin. These in vitro studies confirm its mechanism as a PPARα agonist. |
| ln Vivo |
Clofibric acid (50 mg/kg) treatment 4 days by gavage induces both P450 4A and BFB expression in zones 3 and 2 of the liver acinus in rats. 300 mg/kg of Clofibric acid causes a strong staining of both proteins throughout the liver acinus. Clofibric acid (9,000 ppm) treatment in diet significantly suppresses the growth of OVCAR-3 tumors xenotransplanted s.c. (46%) and significantly prolongs the survival of mice with malignant ascites derived from DISS cells as compared with control. Clofibric acid treatment increases the expression of carbonyl reductase in vivo. Clofibric acid treatment decreases PGE2 level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3–tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis are in solid OVCAR-3 tumors treated by Clofibric acid. |
| Enzyme Assay |
Non-cellular transactivation assays for Clofibric acid involve measuring its activation of PPARα using purified receptor and reporter systems. The compound's EC50 of 50 µM is determined in these assays. These assays confirm its activity as a PPARα agonist.
|
| Cell Assay |
In vitro cell-based assays for Clofibric acid are conducted using hepatocytes to assess its effects on gene expression and lipid metabolism. Cells are treated with the compound, and the expression of PPARα target genes such as L-FABP is measured. These experiments are crucial for confirming its mechanism of action.
|
| Animal Protocol |
50 mg/kg Rats |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
The known metabolites of clofibrate include (2S,3S,4S,5R)-6-[2-(4-chlorophenoxy)-2-methylpropionyl]oxy-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid. Clofibric acid has a molecular weight of 214.65 g/mol. It is a small molecule that is soluble in organic solvents. Detailed pharmacokinetic parameters such as half-life and bioavailability are not extensively documented in standard summaries but would be evaluated in preclinical studies. |
| Toxicity/Toxicokinetics |
Clofibric acid has an established safety profile from its clinical use as the active metabolite of clofibrate. Common side effects include gastrointestinal disturbances, gallstones, and myopathy. Comprehensive toxicological data are available from its clinical use. Clofibric acid is an approved drug metabolite and is available as a research compound.
|
| References |
J Biol Chem.1992 Sep 25;267(27):19051-3;Biochem Pharmacol.1993 May 25;45(10):2045-53.
|
| Additional Infomation |
Clofibric acid is a monocarboxylic acid, a product of isobutyric acid with a p-chlorophenoxy group substituted at the 2-position. It is a metabolite of the drug clofibrate. Clofibrate has various pharmacological effects, including acting as a cholesterol-lowering drug, a lipid-lowering drug, a PPARα agonist, an antitumor drug, a marine xenobiotic metabolite, and a herbicide. It is a monocarboxylic acid, an aromatic ether, and belongs to the monochlorobenzene class of compounds. Its function is related to that of isobutyric acid. Clofibrate is a bioactive metabolite and a lipid-lowering drug.
Clofibric Acid (Chlorofibrinic acid) is a PPARα agonist and the biologically active metabolite of clofibrate. It induces up-regulation of genes involved in peroxisome proliferation and lipid metabolism. Clofibric acid is used as an antilipemic agent. It is an approved drug metabolite and is available as a research compound. |
| Molecular Formula |
C10H11CLO3
|
|
|---|---|---|
| Molecular Weight |
214.65
|
|
| Exact Mass |
214.039
|
|
| CAS # |
882-09-7
|
|
| Related CAS # |
Clofibric acid-d4;1184991-14-7
|
|
| PubChem CID |
2797
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.3±0.1 g/cm3
|
|
| Boiling Point |
324.1±17.0 °C at 760 mmHg
|
|
| Melting Point |
120-122 °C(lit.)
|
|
| Flash Point |
149.8±20.9 °C
|
|
| Vapour Pressure |
0.0±0.7 mmHg at 25°C
|
|
| Index of Refraction |
1.541
|
|
| LogP |
2.72
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
3
|
|
| Rotatable Bond Count |
3
|
|
| Heavy Atom Count |
14
|
|
| Complexity |
207
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
CC(C)(OC1=CC=C(Cl)C=C1)C(O)=O
|
|
| InChi Key |
TXCGAZHTZHNUAI-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C10H11ClO3/c1-10(2,9(12)13)14-8-5-3-7(11)4-6-8/h3-6H,1-2H3,(H,12,13)
|
|
| Chemical Name |
2-(4-chlorophenoxy)-2-methylpropanoic acid
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 43 mg/mL (200.3 mM)
Water: 1 mg/mL (Insoluble) Ethanol: 43 mg/mL (200.3 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.65 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (11.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.6587 mL | 23.2937 mL | 46.5875 mL | |
| 5 mM | 0.9317 mL | 4.6587 mL | 9.3175 mL | |
| 10 mM | 0.4659 mL | 2.3294 mL | 4.6587 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 |
| NCT01527318 | Completed | Drug: Fibrate treatment | Neutral Lipid Storage Disease | Maastricht University Medical Center | August 2011 | Phase 4 |
| NCT03586674 | Completed | Drug: Lipanthyl Drug: Ursogal |
Chronic Cholestasis | Hoda A. Atta | November 1, 2017 | Phase 2 |
| NCT00243672 | Withdrawn | Drug: Atorvastatin Drug: Gemfibrozil |
Atherosclerosis | University Hospital Muenster | October 2005 | Phase 4 |
| NCT00491400 | Terminated Has Results | Drug: Fenofibrate Drug: Atorvastatin |
Diabetes Mellitus Metabolic Syndrome |
Boston University | September 2005 | Not Applicable |
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
