| Targets |
Peroxisome Proliferator-Activated Receptor alpha (PPARalpha). As a peroxisome proliferator, Methyl clofenapate activates PPARalpha, leading to the transcriptional activation of genes involved in peroxisomal fatty acid beta-oxidation and lipid metabolism.
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|---|---|
| ln Vitro |
This entry is not available. As a general principle for PPARalpha agonists, they bind to PPARalpha with high affinity in the nanomolar to low micromolar range in cell-free ligand-binding domain assays, leading to receptor activation and recruitment of coactivator proteins.
|
| ln Vivo |
Methyl clofenapate (Clofenapate methyl ester; MCP) is a peroxisome proliferator that can induce hypolipidemia, peroxisome proliferation, and hepatocarcinogenesis. In Syrian hamster embryo cells, Methyl clofenapate is used to study morphological transformation and intercellular communication.
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| Enzyme Assay |
A general cell-free protocol for PPARalpha ligand-binding domain (LBD) assay: The recombinant human PPARalpha LBD protein (GST-tagged) is incubated with a fluorescently labeled PPARalpha ligand (e.g., Fluoromone PPARalpha Green) in a buffer (100 mM potassium phosphate, pH 7.4, 100 ug/mL BSA) at room temperature for 2 hours. Varying concentrations of the test compound (0.1 nM to 100 uM) are added to compete with the tracer. The change in fluorescence polarization (FP) is measured to calculate the IC₅0, which is then converted to Kᵢ using the Cheng-Prusoff equation.
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| Cell Assay |
A general cellular protocol for PPARalpha transactivation assay: CV-1 cells are seeded in 96-well plates and co-transfected with a PPARalpha expression plasmid and a luciferase reporter plasmid containing a peroxisome proliferator response element (PPRE). After 24 hours, the cells are treated with various concentrations of Methyl clofenapate (0.001-100 uM) for 24 hours. Cells are then lysed, and luciferase activity is measured using a luminometer. EC₅0 values are calculated from the dose-response curve, and the fold induction relative to vehicle control is determined.
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| Animal Protocol |
A general animal protocol for studying peroxisome proliferation: Male Sprague-Dawley rats are administered Methyl clofenapate via oral gavage at doses of 25, 50, and 100 mg/kg/day for 14 days. Body weight and food consumption are monitored daily. At the end of the study, the liver is excised, weighed, and processed for histopathological examination (e.g., H&E staining to assess hepatomegaly and peroxisome proliferation). Electron microscopy is performed to quantify the number and size of peroxisomes in hepatocytes. Serum lipid profiles (triglycerides and cholesterol) are measured using commercial kits to evaluate hypolipidemic effects.
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| ADME/Pharmacokinetics |
This entry is not available.
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| Toxicity/Toxicokinetics |
General toxicity protocol for peroxisome proliferators: Methyl clofenapate is known to induce hepatocarcinogenesis in rats and mice following chronic administration. In a 90-day repeated-dose oral toxicity study in rats, doses of 10, 50, and 250 mg/kg/day would be administered. Endpoints include clinical signs, body weight, serum liver enzymes (ALT, AST, ALP), bilirubin, and histopathology of the liver. An increase in liver weight, hepatocellular hypertrophy, and the formation of peroxisomes (eosinophilic granules) would be observed. Long-term studies (104 weeks) demonstrate that hepatocarcinogenesis is a species-specific effect observed primarily in rodents.
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| References | |
| Additional Infomation |
Methylclofenamic acid is a white powder. (NTP, 1992)
An oral lipid-lowering drug mainly used in dogs and rats. Methyl clofenapate is known as ICI-54856 methyl ester or propanoic acid, 2-((4'-chloro(1,1'-biphenyl)-4-yl)oxy)-2-methyl-, methyl ester. The molecular formula is C1₇H1₇ClO3, and the molecular weight is 304.77. The compound is soluble in DMSO at 100 mg/mL (328.12 mM) and is stored at -20degC. The melting point is 90degC. Methyl clofenapate is used as a positive control in studies of peroxisome proliferation and is a model compound for understanding the biological effects of fibrate-class drugs. |
| Exact Mass |
304.087
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|---|---|
| CAS # |
21340-68-1
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| PubChem CID |
30602
|
| Appearance |
Solid powder
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| Density |
1.171g/cm3
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| Boiling Point |
407ºC at 760 mmHg
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| Flash Point |
151.5ºC
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| Vapour Pressure |
7.77E-07mmHg at 25°C
|
| Index of Refraction |
1.548
|
| LogP |
4.337
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
21
|
| Complexity |
340
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
CLJAWWBXVXWHFD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H17ClO3/c1-17(2,16(19)20-3)21-15-10-6-13(7-11-15)12-4-8-14(18)9-5-12/h4-11H,1-3H3
|
| Chemical Name |
methyl 2-[4-(4-chlorophenyl)phenoxy]-2-methylpropanoate
|
| Synonyms |
Clofenapate methyl ester; MCP
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 100 mg/mL (328.12 mM; with sonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (16.41 mM) in 10% DMSO 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; sonication.
For example, if 1 mL of working solution, add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
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.
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