| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Icosabutate is a synthetic derivative of eicosapentaenoic acid (EPA) that has been engineered to overcome the liver-targeting limitations of unmodified EPA. It improves insulin sensitivity, reduces hepatitis and fibrosis, and lowers triglycerides. It is a PPARα and PPARγ agonist.
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| ln Vitro |
In vitro, Icosabutate acts as a PPARα and PPARγ agonist, modulating gene expression involved in lipid metabolism and inflammation. It reduces the expression of pro-inflammatory cytokines and increases fatty acid oxidation, contributing to its beneficial effects on liver and metabolic health.
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| ln Vivo |
Oral gavage of 100 mg/kg of icosalbutanil produced portal plasma flow rates (522 mL/h) that were significantly higher than mesenteric lymph fluid flow rates (0.5 mL/h). This suggests that icosalbutanol is almost entirely absorbed via the lymphatic route through the portal vein (>99%) in 8-week-old male Wistar rats [1]. Icosalbutanil ([14-C]-Icosalbutanil; oral gavage; 100 mg/kg; once) demonstrated peak radioactivity concentrations in most tissues 4–8 hours after administration (radiactivity levels in most other tissues are lower than those in the plasma of male albino Wistar rats [1]). Icosalbutinate (dietary administration; 135 mg/kg/day; 5 weeks) significantly improved glucose tolerance following oral glucose loading, significantly reducing AUC (0–120 min) by 60%, without affecting body weight, and lowering Plasma alanine aminotransferase (ALT) levels improve glucose metabolism by significantly lowering blood glucose, hemoglobin A1c, plasma insulin, and HOMA-IR in mice (-50%, -47%, -76%, and -87%, respectively) [ 1”. Oral icoxabutate (112 mg/kg/day; 20 weeks) inhibited hepatocellular hypertrophy (-82%) and microvesicular steatosis (-35%) but not macrovesicular steatosis. Despite a similar decrease in liver inflammatory cell aggregates, only icosabutate decreased the amount of liver collagen after 20 weeks of treatment [1].
In vivo, Icosabutate is well-tolerated and improves the cardiovascular risk profile in statin-treated patients with residual hypertriglyceridemia. It inhibits NASH (non-alcoholic steatohepatitis) liver inflammation and fibrosis, reduces triglycerides, and improves insulin sensitivity. |
| Enzyme Assay |
The binding of Icosabutate to PPARα and PPARγ can be assessed using in vitro binding assays. Recombinant PPAR proteins are incubated with a radiolabeled ligand (e.g., [³H]-GW409544 for PPARα) and varying concentrations of Icosabutate. The Ki values are calculated from competitive binding curves.
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| Cell Assay |
The functional activity of Icosabutate is assessed in cells expressing PPARα or PPARγ, such as HepG2 cells. Cells are treated with the compound, and the expression of PPAR target genes (e.g., CPT1A for PPARα, FABP4 for PPARγ) is measured by qPCR. The compound's ability to activate PPAR-mediated transcription is determined.
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| Animal Protocol |
Animal/Disease Models: 6-8 weeks old male ob/ob mice [1]
Doses: 135 mg/kg Route of Administration: 135 mg/kg/day, administered through diet; 5-week Experimental Results: Improved glucose metabolism and insulin resistance. Animal/Disease Models: 8-15 weeks old male APOE*3 Leiden.CETP mice, fed a high-fat and high-cholesterol diet [1] Doses: 112 mg/kg/day Route of Administration: po (oral gavage); 20-week Experimental Results: Improved microbiome Alveolar steatosis, liver inflammation, and fibrosis. In vivo efficacy is evaluated in animal models of NASH, such as mice fed a high-fat diet or a methionine-choline-deficient diet. Icosabutate is administered orally, and markers of liver inflammation (e.g., serum ALT, inflammatory cytokines), fibrosis (e.g., collagen deposition), and metabolic parameters (e.g., triglycerides, insulin sensitivity) are measured. |
| ADME/Pharmacokinetics |
As an orally active small molecule, Icosabutate is expected to have good oral bioavailability. It is structurally engineered to improve liver targeting, suggesting favorable distribution to the liver. Its pharmacokinetic properties support once-daily dosing.
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| Toxicity/Toxicokinetics |
Icosabutate is well-tolerated. As with other omega-3 fatty acids, potential side effects may include gastrointestinal disturbances, such as nausea and diarrhea. However, its engineered structure may minimize these effects.
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| References |
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| Additional Infomation |
Eicosapentaenoic acid (Icosabutate) is being investigated in the clinical trial NCT02373176 ([14C]eicosapentaenoic acid - Phase I absorption, metabolism, and excretion study).
Drug indication Treatment of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis. Icosabutate is an investigational drug being developed for the treatment of NASH and hypertriglyceridemia. It has been evaluated in clinical trials and has shown promise in improving cardiovascular risk profiles. It is not yet approved for clinical use. |
| Molecular Formula |
C24H38O3
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|---|---|
| Molecular Weight |
374.56
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| Exact Mass |
374.282
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| CAS # |
1253909-57-7
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| PubChem CID |
78210211
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| Appearance |
Colorless to light yellow liquid
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| Density |
0.9±0.1 g/cm3
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| Boiling Point |
496.5±45.0 °C at 760 mmHg
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| Flash Point |
157.1±22.2 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
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| Index of Refraction |
1.504
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| LogP |
7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
27
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| Complexity |
484
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(O)(=O)C(OCCCC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CC)CC
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| InChi Key |
VOGXDRFFBBLZBT-AAQCHOMXSA-N
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| InChi Code |
InChI=1S/C24H38O3/c1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22-27-23(4-2)24(25)26/h5-6,8-9,11-12,14-15,17-18,23H,3-4,7,10,13,16,19-22H2,1-2H3,(H,25,26)/b6-5-,9-8-,12-11-,15-14-,18-17-
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| Chemical Name |
2-[(5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoxy]butanoic acid
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| Synonyms |
PRB01022; PRC-4016; PRB-01022
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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 : ~100 mg/mL (~266.98 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.67 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 (6.67 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (6.67 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 | 2.6698 mL | 13.3490 mL | 26.6980 mL | |
| 5 mM | 0.5340 mL | 2.6698 mL | 5.3396 mL | |
| 10 mM | 0.2670 mL | 1.3349 mL | 2.6698 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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