| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
ntacapone sodium targets and inhibits catechol-O-methyltransferase (COMT). This enzyme is widely distributed in mammalian tissues including the liver, kidneys, heart, intestine, nervous system (especially glial cells), and catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to substrates containing a catechol structure. Entacapone exhibits an IC₅₀ value of 151 nM against COMT. In vivo, a single 200 mg oral dose produces an average 65% inhibition of erythrocyte COMT activity, with up to 82% maximum inhibition at 800 mg, returning to baseline within 8 hours.
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| ln Vitro |
In Hep-G2 cells, entacapone sodium salt (50 μM, 48 hours) increases the quantity of m6A on mRNA. In Hep-G2 cells treated with sodium sodium salt, it has no effect on the enzymatic activity of RNA m6A demethylase AlkB homolog 5 (ALKBH5) or 10-11 translocating methylcytosine dioxygenase 1 (TET1), nor does it change the patterns of histone methylation or entaca DNA methylation [2].
Entacapone sodium is a specific, potent, and reversible inhibitor of COMT with an IC₅₀ of 151 nM. Its inhibitory mechanism involves competing with catechol-structured substrates for the methyl binding site of the enzyme, thereby blocking the peripheral metabolism of levodopa. |
| ln Vivo |
Entacapone sodium salt causes a dose-response effect when taken orally (600 mg/kg daily for 3–9 weeks). The mice treated with entacapone sodium salt showed comparable reductions in food intake fat mass and fat mass ratio after three weeks, and they lost 10.1% of their body weight in comparison to the control group. Moreover, entacapone sodium salt increases mice's energy expenditure while lowering their triglycerides (10.2%), low-density lipoprotein cholesterol (31.0%), and total cholesterol (17.6%) [2].
Parkinson's Disease Rat Model: In 6-hydroxydopamine-unilaterally lesioned hemiparkinsonian rats, entacapone (30 mg/kg) coadministered with levodopa (25 mg/kg) twice daily for 22 days potentiated the long-duration response to levodopa, lasting for at least 7 days after treatment discontinuation, but did not modify apomorphine-induced rotational behavior or striatal molecular changes. Erythrocyte COMT Inhibition: In rat in vivo studies, the degree of COMT inhibition in erythrocytes correlated with pharmacokinetic exposure following oral entacapone administration. The inhibitory Emax model demonstrated that a plateau of COMT inhibition near Emax is attained at plasma concentrations below 2000 ng/ml. Different formulations showed varying oral bioavailability (solution pH 7.4: 34.8%; suspension: 8.9%), with correspondingly higher degrees of COMT inhibition. |
| Enzyme Assay |
COMT inhibitory activity of entacapone is typically assessed by measuring COMT enzyme activity in erythrocytes. In healthy volunteer studies, blood samples are collected after oral administration, erythrocytes are isolated, and COMT methylation activity toward substrates is measured. Inhibition percentage relative to baseline is calculated. Results show an average 65% inhibition at 200 mg and 82% maximum inhibition at 800 mg, with a linear dose-inhibition relationship.
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| Animal Protocol |
6-OHDA Lesioned Parkinson's Disease Rat Model: Male Sprague-Dawley rats (220-240 g) receive a unilateral injection of 6-hydroxydopamine (8 μg in 4 μL saline with 0.02% ascorbate) into the left medial forebrain bundle. Complete lesion criteria include apomorphine-induced rotation >100 turns. Lesioned rats are treated twice daily with levodopa (25 mg/kg) + entacapone (30 mg/kg) or vehicle for 22 days via intraperitoneal injection. Striatal preproenkephalin, preprodynorphin, and D3 receptor mRNA expression, as well as subthalamic cytochrome oxidase and nigral glutamic acid decarboxylase mRNA, are detected by in situ hybridization.
Bioavailability Study: Rats are orally administered various entacapone formulations (suspension, solution, HP-β-CD solution, etc.). Plasma concentrations and erythrocyte COMT inhibition are measured, and concentration-effect relationships are analyzed using the Emax model.
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| ADME/Pharmacokinetics |
Entacapone has a molecular weight of 305.29 (free acid) or 327.27 (sodium salt). Following oral administration, entacapone is rapidly absorbed from the gastrointestinal tract, with peak erythrocyte COMT inhibition occurring approximately 1 hour after a 200 mg dose. Its effects are primarily peripheral, with minimal CNS penetration. When coadministered with levodopa, entacapone prolongs the half-life of levodopa, resulting in greater and more sustained plasma levodopa levels. In nanoformulation studies, free entacapone exhibits a half-life (t₁/₂) of 0.704 hours and an AUC₀–∞ of 2227.5 ng·h/mL. Entacapone is soluble in DMSO at 54 mg/mL (176.88 mM), insoluble in water, and has limited solubility in ethanol (2 mg/mL). Storage conditions: powder is stable for 3 years at -20°C.
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| Toxicity/Toxicokinetics |
Clinical Side Effects: When used as a drug, entacapone's side effects are primarily related to increased levodopa exposure, including dyskinesias, nausea, diarrhea, orthostatic hypotension, sleep disturbances, and characteristic orange-colored urine. Entacapone is not associated with hepatotoxicity, making it preferred over tolcapone.
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| References |
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| Additional Infomation |
Entacapone sodium is different from entacapone free acid; the former is provided as a sodium salt and has a different molecular weight and physicochemical properties. In clinical practice, entacapone is only approved as an adjunct to levodopa/carbidopa therapy and is ineffective in patients who do not respond to levodopa. Its peripherally selective mechanism of action makes it superior to tolcapone, which carries a risk of hepatotoxicity. Stalevo® is a combination formulation of levodopa, carbidopa, and entacapone that simplifies the dosing regimen.
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| Molecular Formula |
C₁₄H₁₄N₃NAO₅
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|---|---|
| Molecular Weight |
327.27
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| Exact Mass |
327.083
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| CAS # |
1047659-02-8
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| Related CAS # |
Entacapone;130929-57-6;(E)-Entacapone-d10
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| PubChem CID |
78357787
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.742
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
500
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN(CC)C(=O)/C(=C/C1=CC(=C(C(=C1)O)[O-])[N+](=O)[O-])/C#N.[Na+]
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| InChi Key |
UMQUSXKIIWDDTK-OAZHBLANSA-M
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| InChi Code |
InChI=1S/C14H15N3O5.Na/c1-3-16(4-2)14(20)10(8-15)5-9-6-11(17(21)22)13(19)12(18)7-9;/h5-7,18-19H,3-4H2,1-2H3;/q;+1/p-1/b10-5+;
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| Chemical Name |
sodium;4-[(E)-2-cyano-3-(diethylamino)-3-oxoprop-1-enyl]-2-hydroxy-6-nitrophenolate
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| Synonyms |
Entacapone sodium salt; 1047659-02-8; Entacapone (sodium salt); Sodium (E)-4-(2-cyano-3-(diethylamino)-3-oxoprop-1-en-1-yl)-2-hydroxy-6-nitrophenolate; sodium;4-[(E)-2-cyano-3-(diethylamino)-3-oxoprop-1-enyl]-2-hydroxy-6-nitrophenolate;
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0556 mL | 15.2779 mL | 30.5558 mL | |
| 5 mM | 0.6111 mL | 3.0556 mL | 6.1112 mL | |
| 10 mM | 0.3056 mL | 1.5278 mL | 3.0556 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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