| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary molecular target of Mevinolinic acid is HMG-CoA reductase (EC 1.1.1.34), the enzyme that catalyzes the conversion of HMG-CoA to mevalonate. Mevinolinic acid acts as a competitive inhibitor with respect to the substrate HMG-CoA, with a Ki of 0.6 nM. This inhibition blocks cholesterol synthesis and upregulates LDL receptor expression in hepatocytes, leading to increased clearance of LDL cholesterol from the bloodstream.
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|---|---|
| ln Vitro |
In vitro, Mevinolinic acid inhibits partially purified activated HMG-CoA reductase with a competitive Ki of 0.6 nM. In HepG2 cells, mevinolin (37 μM) inhibits cholesterol biosynthesis by greater than 85% and decreases total cell cholesterol from 36.1 to 27.4 μg/mL of cell protein. The concentration required to inhibit HMG-CoA reductase by 50% in HepG2 cells is 29 nM.
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| ln Vivo |
In vivo, orally administered sodium mevinolinate is an active inhibitor of cholesterol synthesis in the rat, with a 50% inhibitory dose of 46 μg/kg in an acute assay. In dogs, treatment with mevinolin at 8 mg/kg per day for 3 weeks results in a 29.3 ± 2.5% lowering of plasma cholesterol. Mevinolinic acid is the active form responsible for the cholesterol-lowering effects of lovastatin.
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| Enzyme Assay |
For HMG-CoA reductase inhibition assays, partially purified enzyme is incubated with Mevinolinic acid at various concentrations in the presence of NADPH and HMG-CoA. The reaction is initiated by the addition of substrate, and the decrease in NADPH absorbance at 340 nm is measured spectrophotometrically to determine enzyme activity. Ki values are calculated by Lineweaver-Burk or Dixon plot analysis.
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| Cell Assay |
For in vitro cell assays, HepG2 human hepatoma cells are cultured in appropriate media and treated with Mevinolinic acid at various concentrations. Cholesterol biosynthesis is measured by incorporation of radiolabeled acetate or by direct measurement of cholesterol mass. For HMG-CoA reductase activity, cell lysates are prepared, and enzyme activity is measured by the NADPH-dependent reduction of HMG-CoA.
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| Animal Protocol |
For in vivo studies, rats or dogs receive sodium mevinolinate or lovastatin by oral gavage at doses of 8 mg/kg per day or higher. Plasma cholesterol levels are measured at baseline and after 3 weeks of treatment. Acute cholesterol synthesis assays are performed using radiolabeled precursors. Liver tissue is collected for measurement of HMG-CoA reductase activity and LDL receptor expression.
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| References | |
| Additional Infomation |
Mevastatinic acid is a polyketide compound obtained by the hydrolysis of lovastatin's pyranone ring. It is an Aspergillus metabolite, an EC 1.1.1.34/EC 1.1.1.88 (hydroxymethylglutaryl-CoA reductase) inhibitor, a teratogen, and a drug metabolite. It is a carbon-bicyclic compound, a dihydroxy monocarboxylic acid, a polyketide compound, and a fatty acid ester. Its function is related to lovastatin and (S)-2-methylbutyric acid. It is the conjugate acid of mevastatinic acid. Lovastatinic acid has been reported to be detected in Euglena and Aspergillus terreus, and relevant data are available. Lovastatinic acid is the active acidic form of lovastatin. In vivo, lovastatin is hydrolyzed to its β-hydroxy acid active form.
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| Molecular Formula |
C24H38O6
|
|---|---|
| Molecular Weight |
422.56
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| Exact Mass |
447.268
|
| CAS # |
75225-51-3
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| Related CAS # |
Lovastatin hydroxy acid sodium;75225-50-2
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| PubChem CID |
64727
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| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.14g/cm3
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| Boiling Point |
602.3ºC at 760 mmHg
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| Flash Point |
199.1ºC
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| Index of Refraction |
1.537
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| Source |
Endogenously produced metabolite: Human Gut Microbiota Metabolites
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| LogP |
2.38
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
30
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| Complexity |
654
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| Defined Atom Stereocenter Count |
8
|
| SMILES |
CCC(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC(CC(CC(=O)O)O)O)C
|
| InChi Key |
QLJODMDSTUBWDW-BXMDZJJMSA-N
|
| InChi Code |
InChI=1S/C24H38O6/c1-5-15(3)24(29)30-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-18(25)12-19(26)13-22(27)28/h6-7,10,14-16,18-21,23,25-26H,5,8-9,11-13H2,1-4H3,(H,27,28)/t14-,15-,16-,18+,19+,20-,21-,23-/m0/s1
|
| Chemical Name |
(3R,5R)-7-[(1S,2S,6R,8S,8aR)-2,6-dimethyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid
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| Synonyms |
MSD 803 acid; Monacolinic K acid; Mevinolinic acid
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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 | 2.3665 mL | 11.8326 mL | 23.6653 mL | |
| 5 mM | 0.4733 mL | 2.3665 mL | 4.7331 mL | |
| 10 mM | 0.2367 mL | 1.1833 mL | 2.3665 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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