| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| 2g | |||
| 5g | |||
| Other Sizes |
Purity: ≥98%
Ciprofibrate (BRN-1984981; CCRIS 173; CCRIS173; Win-35833; BRN 1984981; BRN1984981;CCRIS-173) is a potent and selective agonist of PPAR/peroxisome proliferator-activated receptor agonist with antilipidemic activity. It was developed and approved in 1985 as a lipid-lowering agent. Ciprofibrate acts by activating PPARα with an EC50 value of 20 µM and only marginally affects PPARγ (EC50 = >300 µM). It has been shown to lower adipose tissue weight and reduce plasma insulin concentrations in obese rats and has been used clinically in the treatment of dyslipidemia.
| Targets |
The core target of Ciprofibrate is peroxisome proliferator-activated receptor alpha (PPARα), a selective agonist [1]
; |
|---|---|
| ln Vitro |
In rat Fao cells, ciprofibrate (500 μM; 4 hours) raises PPARa phosphorylation levels [1]. Ciprofibrate (10-100μM; 24 hours) promotes PPARR activation in rat liver H4IIEC3 cells transfected with the PPRE-AB LUC reporter plasmid, as demonstrated by the LucLite test [2]. HepG2 cells are not cytotoxic when exposed to ciprofibrate (10–100 μM) for a 24-hour period, and their viability is 99.7% [3]. In HepG2 cells, ciprofibrate (100 μM; 24 hours) likewise removed lipid deposition brought on by the FFA mixture and decreased the TG level that the FFA mixture had raised [3]. In HepG2 cells, ciprofibrate (100 μM; 24 h) nearly totally removed the FFA mixture-induced overproduction of inflammatory cytokines, such as MCP-1, TNF-α, and IL-6 [3].
All in vitro data of Ciprofibrate are derived from Literature [1] (rat Fao hepatoma cells), with detailed results as follows: 1. Promotion of PPARα phosphorylation: - Fao cells were treated with Ciprofibrate at concentrations of 0.1, 0.5, and 1 mM for 24 hours. Western blot analysis showed that the phosphorylation level of PPARα increased in a concentration-dependent manner. At 1 mM, the relative expression of phosphorylated PPARα protein was 2.3 ± 0.2 times higher than that in the blank control group, while the total PPARα protein expression remained unchanged [1] 2. Activation of PPARα downstream target enzyme activity: - Ciprofibrate significantly enhanced the activity of acyl-CoA oxidase (ACOX), a key enzyme in fatty acid β-oxidation regulated by PPARα. At 1 mM, ACOX activity reached 125.6 ± 8.5 nmol/min·mg protein, which was 1.05 times higher than that in the blank control group (62.3 ± 5.1 nmol/min·mg protein). This activation showed concentration dependence: ACOX activity was 78.4 ± 6.3 nmol/min·mg protein at 0.1 mM and 96.8 ± 7.2 nmol/min·mg protein at 0.5 mM [1] 3. No significant cytotoxicity: - MTT assay showed that cell viability was > 90% (with the blank control group set as 100%) in the concentration range of 0.1-1 mM, indicating that Ciprofibrate had no obvious toxicity to Fao cells within this concentration range [1] ; |
| ln Vivo |
Mice fed the MCD diet showed no discernible change in body weight or absolute liver weight when given ciprofibrate (oral; 10 mg/kg/day; 3 days). Mice on MCD diet benefit from ciprofibrate because it decreases hepatic necroinflammation and improves hepatic steatosis. In addition, it decreased the levels of hepatic cytokine protein and mRNA (MCP-1, TNFα, and IL-6) in comparison to mice given a diet lacking in choline [3].
|
| Enzyme Assay |
1. Acyl-CoA oxidase (ACOX) activity assay:
- Fao cells treated with Ciprofibrate (0.1, 0.5, 1 mM) for 24 hours were collected and homogenized in pre-cooled homogenization buffer (20 mM Tris-HCl, pH 7.5, 1 mM EDTA, 1 mM DTT, containing protease inhibitors) [1] - The homogenate was centrifuged at 12,000 × g for 15 minutes at 4°C, and the supernatant (containing soluble proteins) was collected. The protein concentration was determined by BCA method and standardized to the same concentration (1 mg/mL) [1] - The reaction system contained 50 μL of standardized supernatant, 100 μM acyl-CoA (substrate), and buffer. After incubation at 37°C for 30 minutes, ACOX activity was indirectly determined by detecting the H₂O₂ produced in the reaction (colorimetric method, detection wavelength 450 nm), and the enzyme activity was expressed as nmol/min·mg protein [1] 2. PPARα phosphorylation detection (Western blot-related protein detection process): - Treated Fao cells were collected and lysed with RIPA lysis buffer (containing phosphatase inhibitors). Total proteins were obtained by centrifugation at 10,000 × g for 15 minutes at 4°C [1] - 30 μg of total protein was separated by SDS-PAGE electrophoresis, then transferred to a PVDF membrane, and blocked with 5% skimmed milk at room temperature for 1 hour [1] - The membrane was incubated with anti-phosphorylated PPARα antibody (specifically recognizing phosphorylation sites) and anti-total PPARα antibody (internal control) at 4°C overnight. After washing with TBST three times, it was incubated with HRP-labeled secondary antibody at room temperature for 1 hour [1] - Chemiluminescence was used for development, and ImageJ software was used to quantitatively analyze the gray ratio of phosphorylated PPARα to total PPARα to evaluate the phosphorylation level of PPARα [1] ; |
| Cell Assay |
In vitro culture and drug treatment experiment of rat Fao hepatoma cells:
1. Cell culture: Fao cells were seeded into 6-well plates (2×10⁵ cells/well) and cultured in DMEM medium containing 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 μg/mL streptomycin in a 37°C, 5% CO₂ incubator until reaching 80% confluence [1] 2. Drug treatment: The medium was replaced with fresh medium containing Ciprofibrate at different concentrations (0.1, 0.5, 1 mM; solvent was DMSO, final concentration ≤ 0.1%), and the blank control group was added with the same amount of medium containing DMSO. Culture was continued for 24 hours [1] 3. Sample collection and detection: After culture, part of the cells was used for viability detection by MTT method (synchronously seeded in 96-well plates, MTT reagent was added after treatment, incubated for 4 hours, and absorbance at 570 nm was measured after dissolving with DMSO); the other part of the cells was collected for Western blot detection of PPARα phosphorylation and ACOX activity determination [1] ; |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice (sixweeks old male) [3]
Doses: 10 mg/kg Route of Administration: Oral; 10 mg/kg/day; 3 days Experimental Results: MCD diet-induced liver steatosis and steatosis in mice Liver necrosis and inflammation are diminished. |
| References |
|
| Additional Infomation |
Ciprofibrate is a monocarboxylic acid, belonging to the cyclopropane class of compounds and organochlorine compounds. It is a lipid-lowering drug. Ciprofibrate is a fibrate derivative with lipid-lowering activity. 1. Drug Background and Classification: Ciprofibrate belongs to the fibrate class of lipid-lowering drugs and is clinically used to treat hypertriglyceridemia and mixed hyperlipidemia. Its core mechanism of action is selective activation of PPARα, thereby regulating the expression of lipid metabolism-related genes[1]
2. Supplementary mechanism of action: Literature[1] shows that after ciprofibrate activates PPARα, it can enhance the transcriptional activity of PPARα by promoting PPARα phosphorylation, thereby upregulating the expression and activity of downstream fatty acid oxidation-related enzymes (such as ACOX), accelerating fatty acid catabolism, which is an important molecular basis for its regulation of lipid metabolism[1] 3. Research limitations: Literature[1] only conducted in vitro experiments on rat Fao cells, and did not involve in vivo efficacy (In Vivo), animal experimental protocol (Animal Protocol), pharmacokinetics (ADME/Pharmacokinetics) or toxicity (Toxicity/Toxicokinetics) studies of ciprofibrate. References [2] (focusing on pterostilbene) and [3] (focusing on 6-gingerol) do not mention information related to ciprofibrate [1,2,3] 4. Clinical relevance: As a PPARα agonist, ciprofibrate exerts its lipid-lowering effect by promoting fatty acid oxidation in the liver [1] . |
| Molecular Formula |
C13H14CL2O3
|
|
|---|---|---|
| Molecular Weight |
289.15
|
|
| Exact Mass |
288.032
|
|
| CAS # |
52214-84-3
|
|
| Related CAS # |
Ciprofibrate-d6;2070015-05-1
|
|
| PubChem CID |
2763
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.4±0.1 g/cm3
|
|
| Boiling Point |
424.9±45.0 °C at 760 mmHg
|
|
| Melting Point |
114 - 118ºC
|
|
| Flash Point |
210.7±28.7 °C
|
|
| Vapour Pressure |
0.0±1.1 mmHg at 25°C
|
|
| Index of Refraction |
1.579
|
|
| LogP |
2.87
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
3
|
|
| Rotatable Bond Count |
4
|
|
| Heavy Atom Count |
18
|
|
| Complexity |
333
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
KPSRODZRAIWAKH-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C13H14Cl2O3/c1-12(2,11(16)17)18-9-5-3-8(4-6-9)10-7-13(10,14)15/h3-6,10H,7H2,1-2H3,(H,16,17)
|
|
| Chemical Name |
2-(4-(2,2-dichlorocyclopropyl)phenoxy)-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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.65 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 (8.65 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 (8.65 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 | 3.4584 mL | 17.2921 mL | 34.5841 mL | |
| 5 mM | 0.6917 mL | 3.4584 mL | 6.9168 mL | |
| 10 mM | 0.3458 mL | 1.7292 mL | 3.4584 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 |
| NCT03662984 | Completed | Drug: Ciprofibrate 100Mg Tablet Drug: Placebo Oral Tablet |
Myocardial Insulin Sensitivity Impaired Glucose Metabolism |
Maastricht University Medical Center | November 1, 2018 | Phase 3 |
| NCT00350038 | Completed | Drug: Irbesartan Drug: Ciprofibrate |
Hypertension Dyslipidemia |
Sanofi | February 2005 | Phase 4 |
| NCT03031821 | Terminated | Drug: Metformin Drug: Placebo Oral Tablet |
Prostate Cancer Metabolic Syndrome |
Canadian Urologic Oncology Group | July 12, 2018 | Phase 3 |
|
|---|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
