Mevalonolactone

Cat. No.: HY-135700 Purity: 98.0%: Data Sheet
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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 (K_a = 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.

For research use only. We do not sell to patients.

Mevalonolactone Chemical Structure

CAS No. : 19115-49-2

Size	Stock	Quantity
Liquid + Solvent (Highly Recommended)
10 mM * 1 mL in Water ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in Water	In-stock	Estimated Time of Arrival: December 31
Liquid
1 mg	In-stock	Estimated Time of Arrival: December 31
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
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Biological Activity
Purity & Documentation
References
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Description

In Vitro

Mevalonolactone directly binds to recombinant ZNF384 protein with a K_d 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.

Western Blot Analysis^[1]

Cell Line:	AML12 murine hepatocytes
Concentration:	1 μM
Incubation Time:	24 h
Result:	Significantly upregulated GGPPS protein levels in AML12 cells.

In Vivo

Mevalonolactone (10 mM; i.p.; once every 2 days; for 6 consecutive weeks) induces metabolically abnormal obesity in male C57BL/6J mice fed a normal diet. Through upregulating GGPPS, enhancing K-Ras isoprenylation, and ZNF384-mediated transcriptional activation of *Ggpps*, it triggers insulin resistance, impaired glucose homeostasis, increased body and tissue weights, elevated triglyceride levels, as well as altered gene expression in the liver and adipose tissue^[1].
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.

Animal Model:	C57BL/6J (male, 8 weeks old)^[1]
Dosage:	10 mmol/L
Administration:	i.p.; every 2 days; 6 weeks
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.

Animal Model:	C57BL/6J (male, 8 weeks old, high-fat diet-fed for 8 weeks prior to treatment and throughout treatment)^[1]
Dosage:	10 mmol/L
Administration:	i.p.; every 2 days; 6 weeks
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.

Animal Model:	C57BL/6 (8 weeks old)^[3]
Dosage:	200 mg/kg/d
Administration:	p.o.; daily; 14 days
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.

Molecular Weight

130.14

Formula

C₆H₁₀O₃

CAS No.

19115-49-2

Appearance

Liquid (Density: 1.190±0.06 g/cm³)

Color

Colorless to light yellow

SMILES

O=C1C[C@](C)(O)CCO1

Structure Classification

Initial Source

Microorganisms

Pestalotiopsis sp.

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Store at room temperature, keep dry and cool

In solvent	-80°C	1 year
	-20°C	6 months

Solvent & Solubility

In Vitro:

H₂O : ≥ 100 mg/mL (768.40 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	7.6840 mL	38.4202 mL	76.8403 mL
5 mM	1.5368 mL	7.6840 mL	15.3681 mL
10 mM	0.7684 mL	3.8420 mL	7.6840 mL

View the 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.

* 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.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

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Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).

Purity & Documentation

Purity: 98.0%

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Data Sheet (285 KB) SDS (394 KB)

COA (250 KB) HNMR (227 KB)

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.

[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.

Complete Stock Solution Preparation Table

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.