| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Theofibrate activates peroxisome proliferator-activated receptors (PPARs), which play a crucial role in the regulation of fatty acid metabolism and glucose homeostasis. The clofibric acid moiety of Theofibrate is responsible for PPAR activation. Etofylline, the theophylline derivative component, inhibits the activity of hepatic lipase, an enzyme that causes the breakdown of triglycerides into free fatty acids and glycerol. The compound also has agonistic interactions with intimal PGI2, contributing to its antithrombotic effects.
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| ln Vitro |
Theofibrate demonstrates lipid-lowering activity in vitro through its effects on PPAR activation and hepatic lipase inhibition. As a fibrate derivative, it would be expected to regulate the expression of genes involved in lipid metabolism, including those encoding lipoprotein lipase, apolipoproteins, and fatty acid oxidation enzymes. The compound's dual pharmacophore design combines lipid-lowering and antithrombotic activities. Specific in vitro data, including IC50 values and detailed assay conditions, are not extensively provided in the available literature.
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| ln Vivo |
After continuous use five and seven times daily, clofibrate etonophylline (oral; 12 mg/kg) had a moderate effect (12% reduction in decomposition time), with a maximum reduction of 31% and 43% [1].
Theofibrate demonstrates in vivo lipid-lowering and antithrombotic effects. After continuous use five and seven times daily, oral administration of Theofibrate produces lipid-lowering effects. The compound reduces triglyceride levels and increases HDL cholesterol. Its antithrombotic and platelet-aggregation inhibitory activities contribute to its cardiovascular protective effects. The compound is practically insoluble in water at pH 2-7.4 and in cold alcohols. Specific details on dosing regimens, animal models, and efficacy data are not extensively provided. |
| Enzyme Assay |
In vitro enzyme assays for Theofibrate would typically involve measuring PPAR activation and hepatic lipase inhibition. For PPAR activation, a reporter gene assay can be used: cells are transfected with a PPAR-responsive luciferase reporter plasmid and PPAR expression plasmids. Cells are treated with Theofibrate at various concentrations (typically 0.1-100 μM) for 24 hours, and luciferase activity is measured. For hepatic lipase inhibition, enzyme preparations are incubated with triglyceride substrates and varying concentrations of Theofibrate. Free fatty acid release is quantified by colorimetric or fluorometric assays. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
For in vitro cell-based assays, hepatocytes or other cell lines expressing PPARs are cultured in appropriate medium. Cells are treated with Theofibrate at various concentrations (typically 0.1-100 μM) for 24-72 hours. Lipid accumulation is assessed by Oil Red O staining or by measuring cellular triglyceride and cholesterol content. Gene expression of PPAR target genes (e.g., lipoprotein lipase, acyl-CoA oxidase) is measured by qRT-PCR. Cytotoxicity is assessed using MTT or similar assays. The compound's effects on glucose metabolism can be evaluated by measuring glucose uptake or gluconeogenesis in hepatocytes.
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| Animal Protocol |
In vivo animal studies for Theofibrate would typically use rodent models of dyslipidemia, such as high-fat diet-fed rats or genetically modified hyperlipidemic mice. Theofibrate is administered orally at doses determined from pharmacokinetic studies. Blood lipid profiles (triglycerides, total cholesterol, HDL, LDL) are measured before and after treatment. Platelet aggregation is assessed using aggregometry. Thrombosis models (e.g., arterial thrombosis, venous thrombosis) may be used to evaluate antithrombotic effects. Body weight, food intake, and organ weights are monitored. Specific protocols using Theofibrate are not extensively documented in the available literature.
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| ADME/Pharmacokinetics |
Theofibrate is a small molecule with molecular formula C19H21ClN4O5. It is practically insoluble in water at pH 2-7.4 and in cold alcohols. The compound is typically administered orally in its ester form, which enhances its bioavailability. Detailed pharmacokinetic parameters (absorption, distribution, metabolism, excretion, half-life, Cmax, Tmax, AUC) are not extensively characterized in the available literature. As a fibrate derivative, it would be expected to be well absorbed and extensively protein-bound in plasma.
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| Toxicity/Toxicokinetics |
Theofibrate is generally well-tolerated, but like other fibrates, it may have side effects including gastrointestinal disturbances and potential interactions with other medications. The compound has low toxicity in animals. It is a derivative of clofibric acid with antilipemic, antithrombotic, and platelet-aggregation inhibitory activity. Standard toxicology assessments would be required for therapeutic development, including acute, subchronic, and chronic toxicity studies, as well as genotoxicity and reproductive toxicity evaluations. Specific toxicity data are not extensively provided in the available literature.
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| References | |
| Additional Infomation |
Clofibratetofen is an oxypurine drug.
Theofibrate (etofylline clofibrate) is a synthetic small molecule from the fibrate class of lipid-modifying agents. It is a dual pharmacophore combining a clofibric acid moiety with a theophylline (xanthine) derivative via an ester linkage. The compound has lipid-lowering, antithrombotic, and platelet-aggregation inhibitory activities. It activates PPARs and inhibits hepatic lipase. Theofibrate is used in the management of dyslipidemia, reducing triglycerides and increasing HDL cholesterol. No approved status is currently reported in the available literature. Further clinical development may be needed. |
| Molecular Formula |
C19H21CLN4O5
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|---|---|
| Molecular Weight |
420.85
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| Exact Mass |
420.12
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| CAS # |
54504-70-0
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| PubChem CID |
41109
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
615.8±65.0 °C at 760 mmHg
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| Melting Point |
133-135°
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| Flash Point |
326.2±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.618
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| LogP |
2.75
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
653
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C(=O)OCCN1C=NC2=C1C(=O)N(C)C(=O)N2C)OC3=CC=C(C=C3)Cl
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| InChi Key |
KYAKGJDISSNVPZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H21ClN4O5/c1-19(2,29-13-7-5-12(20)6-8-13)17(26)28-10-9-24-11-21-15-14(24)16(25)23(4)18(27)22(15)3/h5-8,11H,9-10H2,1-4H3
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| Chemical Name |
2-(1,3-dimethyl-2,6-dioxopurin-7-yl)ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
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| Synonyms |
Etofyllineclofibrate; Etofylline clofibrate; Theofibrate
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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 : ~52 mg/mL (~123.56 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (5.16 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 21.7 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: ≥ 2.17 mg/mL (5.16 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 21.7 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: ≥ 2.17 mg/mL (5.16 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 | 2.3761 mL | 11.8807 mL | 23.7614 mL | |
| 5 mM | 0.4752 mL | 2.3761 mL | 4.7523 mL | |
| 10 mM | 0.2376 mL | 1.1881 mL | 2.3761 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.
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