Mevalonolactone
Based on 1 Customer Validation
Mevalonolactone is an intermediate metabolite in the eukaryotic mevalonate pathway, serving as the stable δ-lactone form of mevalonate with oral activity. Mevalonolactone exhibits binding affinity for ZNF384 (Ka = 12.6 μM) and inhibitory activity against aconitase (aconitase). Mevalonolactone promotes the nuclear localization of ZNF384 and enhances its binding to the GGPPS promoter. Mevalonolactone induces insulin resistance, disrupts glucose and lipid metabolism, enhances the isoprenylation of K-Ras, and inhibits the activation of the insulin signaling pathway. Mevalonolactone inhibits polypeptide synthesis of HMG-CoA reductase in isolated rat hepatocytes, promotes its degradation, and reduces its enzymatic activity. Mevalonolactone impairs mitochondrial function in rat brains. Mevalonolactone promotes the development of metabolically unhealthy obesity. Mevalonolactone can be used in research related to metabolically abnormal obesity, mevalonic aciduria, HMGCR-related limb-girdle myopathy, and statin-induced myopathy.
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- Purity: 98.0%
- CAS No.: 19115-49-2
- 화학식: C6H10O3
- 분자량:130.14
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보관:
Store at room temperature, keep dry and cool.
In solvent -80°C, 1 year , -20°C, 6 months
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Biological Activity
Mevalonolactone directly binds to recombinant ZNF384 protein with a Kd value of 12.6 μM[1].
Mevalonolactone (1 μM; 24 h) enhances isoprenylation and membrane localization of K-Ras in AML12 cells, upregulates the protein level of GGPPS in cells, and inhibits insulin-stimulated AKT phosphorylation[1].
Mevalonolactone treatment promotes the nuclear localization of ZNF384 in cultured cells and enhances the binding of ZNF384 to the Ggpps promoter in cells[1].
Mevalonolactone (1 mM; added 50 seconds pre-Ca2+, measurements taken 100 seconds post-Ca2+) reduces the mitochondrial membrane potential of Ca2+-loaded rat brain mitochondria[2].
Mevalonolactone (1 mM; added 50 seconds pre-Ca2+, measurements 100 seconds post-Ca2+) reduces the mitochondrial matrix NAD (P) H content in Ca2+-loaded rat brain mitochondria, induces swelling in Ca2+-loaded rat brain mitochondria, and decreases the Ca2+ retention capacity of rat brain mitochondria[2].
Mevalonolactone (1-2 mM; 30-minute incubation at 37°C) induces lipid peroxidation in rat brain mitochondria, significantly increases MDA levels, and inhibits aconitase activity in rat brain mitochondria[2].
Mevalonolactone (1 μM-10 mM; 5 min-3 h) specifically reduces the activity of HMG-CoA reductase in rat hepatocytes[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:AML12 murine hepatocytes
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Concentration:1 μM
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Incubation Time:24 h
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Result:Significantly upregulated GGPPS protein levels in AML12 cells.
Mevalonolactone (10 mM; i.p.; once every 2 days; for 6 consecutive weeks) exacerbates insulin resistance and glucose-lipid metabolic disorders in male C57BL/6J mice fed a high-fat diet, and promotes metabolically unhealthy obesity[1].
Mevalonolactone (200 mg/kg; p.o.; daily administration; for 14 consecutive days) significantly alleviates statin-induced myopathy symptoms in C57BL/6 mice, restoring their muscle strength, endurance and spontaneous activity to levels close to those of the control group[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 8 weeks old)[1]
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Dosage:10 mmol/L
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Administration:i.p.; every 2 days; 6 weeks
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Result:Increased area under curve for insulin tolerance.
Increased area under curve for glucose tolerance.
Elevated fasting and postprandial blood glucose levels.
Increased body weight, liver weight to body weight ratio, inguinal white adipose tissue weight to body weight ratio, and epididymal white adipose tissue weight to body weight ratio.
Elevated serum and liver triglyceride levels.
Increased lipid accumulation in liver (observed via H&E and Oil Red O staining).
Upregulated hepatic gene expression of Fasn, Scd1, Srebp1c, Cd36, Gpat, and Dgat.
Downregulated hepatic gene expression of Atgl and Hsl.
Reduced hepatic pyruvate levels and Hk1 expression.
Inhibited insulin-stimulated AKT phosphorylation in the liver.
Upregulated lipogenesis genes (Fasn, Scd1) in inguinal white adipose tissue.
Downregulated lipolysis-related genes and impaired insulin signaling in epididymal white adipose tissue.
Upregulated 284 hepatic genes and downregulated 412 hepatic genes, with enrichment in insulin response, fatty acid transport, cholesterol synthesis, and insulin signaling pathways (FoxO, PI3K-AKT, AMPK).
Increased membrane localization and prenylation of K-Ras.
Upregulated hepatic GGPPS protein and mRNA levels.
Promoted nuclear localization of ZNF384 and enhanced its binding to the Ggpps promoter.
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Animal Model:C57BL/6J (male, 8 weeks old, high-fat diet-fed for 8 weeks prior to treatment and throughout treatment)[1]
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Dosage:10 mmol/L
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Administration:i.p.; every 2 days; 6 weeks
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Result:Reduced insulin sensitivity and disrupted glucose homeostasis.
Increased body weight gain, liver weight, inguinal white adipose tissue mass, and epididymal white adipose tissue mass compared to high-fat diet controls.
Upregulated hepatic gene expression of Fasn, Scd1, Srebp1c, Gpat, Agpat, and Dgat.
Downregulated hepatic gene expression of Cpt1a, Hsl, and Abhd5.
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Animal Model:C57BL/6 (8 weeks old)[3]
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Dosage:200 mg/kg/d
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Administration:p.o.; daily; 14 days
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Result:Improved grip strength, hanging wire performance, total movement, ambulatory movement, voluntary wheel max speed, wheel time sum, wheel runs sum, and wheel total distance significantly compared to cerivastatin alone.
Improved grip strength, hanging wire performance, total movement, ambulatory movement, and voluntary wheel runs sum significantly compared to simvastatin alone.
Showed no overt signs of necrosis or inflammation in diaphragm, gastrocnemius, or quadriceps muscle histology.
Chemical Information
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CAS No. 19115-49-2
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Appearance Liquid (Density: 1.190±0.06 g/cm3)
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분자량 130.14
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화학식 C6H10O3
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Color Colorless to light yellow
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SMILES
O=C1C[C@](C)(O)CCO1
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Structure Classification
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Initial Source
Pestalotiopsis sp.
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Store at room temperature, keep dry and cool
In solvent -80°C 1 year -20°C 6 months
용액&용해도
H2O : ≥ 100 mg/mL (768.40 mM)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
순도&문서
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Data Sheet (285 KB)
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SDS (394 KB)
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Handling Instructions (2659 KB)
References
[1]. Nie HY, et al. Elevated mevalonolactone from Ruminococcus torques contributes to metabolically unhealthy obesity development. J Biol Chem. 2025;301(6):110281. [Content Brief]
[2]. Cecatto C, et al. Mevalonolactone disrupts mitochondrial functions and induces permeability transition pore opening in rat brain mitochondria: Implications for the pathogenesis of mevalonic aciduria. Neurochem Int. 2017;108:133-145. [Content Brief]
[3]. Yogev Y, et al. Limb girdle muscular disease caused by HMGCR mutation and statin myopathy treatable with mevalonolactone. Proc Natl Acad Sci U S A. 2023;120(7):e2217831120. [Content Brief]
[4]. Edwards PA, et al. Mevalonolactone inhibits the rate of synthesis and enhances the rate of degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat hepatocytes. J Biol Chem. 1983;258(12):7272-7275. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O | 1 mM | 7.6840 mL | 38.4202 mL | 76.8403 mL | 192.1008 mL |
| 5 mM | 1.5368 mL | 7.6840 mL | 15.3681 mL | 38.4202 mL | |
| 10 mM | 0.7684 mL | 3.8420 mL | 7.6840 mL | 19.2101 mL | |
| 15 mM | 0.5123 mL | 2.5613 mL | 5.1227 mL | 12.8067 mL | |
| 20 mM | 0.3842 mL | 1.9210 mL | 3.8420 mL | 9.6050 mL | |
| 25 mM | 0.3074 mL | 1.5368 mL | 3.0736 mL | 7.6840 mL | |
| 30 mM | 0.2561 mL | 1.2807 mL | 2.5613 mL | 6.4034 mL | |
| 40 mM | 0.1921 mL | 0.9605 mL | 1.9210 mL | 4.8025 mL | |
| 50 mM | 0.1537 mL | 0.7684 mL | 1.5368 mL | 3.8420 mL | |
| 60 mM | 0.1281 mL | 0.6403 mL | 1.2807 mL | 3.2017 mL | |
| 80 mM | 0.0961 mL | 0.4803 mL | 0.9605 mL | 2.4013 mL | |
| 100 mM | 0.0768 mL | 0.3842 mL | 0.7684 mL | 1.9210 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Mevalonolactone Related Classifications
HY-135700 Related Classifications
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