| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
Mevalonate-pyrophosphate decarboxylase is the primary molecular target. This enzyme catalyzes the final step of the mevalonate pathway, converting mevalonate pyrophosphate to isopentenyl pyrophosphate (IPP), a key building block for cholesterol, dolichol, ubiquinone (CoQ10), and protein prenylation. Inhibition of this enzyme blocks the synthesis of all downstream isoprenoid products.
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| ln Vitro |
In cell-free assays, 6-Fluoromevalonate acts as a competitive inhibitor of mevalonate-pyrophosphate decarboxylase, with an IC50 in the low micromolar range (1-10 uM). It blocks the conversion of mevalonate pyrophosphate to IPP, leading to depletion of cholesterol and other isoprenoids. The inhibition is irreversible, as the fluorine atom prevents the decarboxylation reaction.
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| ln Vivo |
In vivo, 6-Fluoromevalonate (10-50 mg/kg IP in mice) inhibits sterol synthesis and reduces plasma cholesterol levels. Importantly, it has been used to study the role of the mevalonate pathway in lymphocyte proliferation, where it was demonstrated that mevalonate or one of its phosphorylated derivatives is essential for cell growth. It also affects brain tumor-initiating cell growth.
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| Enzyme Assay |
For enzyme inhibition studies, mevalonate-pyrophosphate decarboxylase (purified from liver or recombinant) is incubated with varying concentrations of 6-Fluoromevalonate (0-100 uM) in an assay buffer (50 mM potassium phosphate, pH 7.0, containing 5 mM MgCl2, 0.1 mM NADPH) and the substrate mevalonate pyrophosphate. Activity is measured by quantifying the production of IPP or the consumption of NADPH by spectrophotometry at 340 nm.
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| Cell Assay |
For cellular studies, cells (e.g., lymphocytes, cancer cells, or primary neurons) are treated with 6-Fluoromevalonate (1-100 uM) for 24-72 hours. Mevalonate pathway inhibition is assessed by measuring cell proliferation (by MTT or [3H]-thymidine incorporation), monitoring protein prenylation (by western blot for Rab or Ras GTPases), or by measuring cholesterol synthesis using [14C]-acetate incorporation.
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| Animal Protocol |
In animal models, 6-Fluoromevalonate is administered by intraperitoneal injection (10-100 mg/kg in saline or PBS). Tissue samples (liver, brain, tumor) are collected after 2-24 hours to measure sterol synthesis by [3H] or [14C]-acetate incorporation. In vivo efficacy studies in mouse xenograft models (e.g., patient-derived brain tumor-initiating cells) involve daily IP injections for 2-4 weeks to assess tumor growth inhibition.
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| ADME/Pharmacokinetics |
PK properties: 6-Fluoromevalonate is a small, polar molecule (MW 148.13) with good water solubility. After IP administration in rodents, it is rapidly absorbed (Tmax 15-30 min) and distributed to tissues, with a plasma half-life of 1-2 hours. It is metabolized to the active pyrophosphate form intracellularly. Formulation is in saline or PBS for injection.
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| Toxicity/Toxicokinetics |
Toxicity of 6-Fluoromevalonate is moderate. At high doses (>100 mg/kg), it can cause growth arrest and apoptosis in rapidly dividing cells due to depletion of essential isoprenoids (dolichol, ubiquinone, and prenylated proteins). It is not approved for human use. Standard safety precautions for enzyme inhibitors should be observed.
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| Additional Infomation |
4-(fluoromethyl)-4-hydroxy-2-oxacyclohexanone is a δ-lactone.
6-Fluoromevalonate is a valuable research tool for studying the mevalonate pathway, which is a key target for cholesterol-lowering drugs (statins) and for anticancer agents. Statins inhibit HMG-CoA reductase, an upstream enzyme; FMev works downstream, providing a distinct mechanism for dissecting the roles of specific isoprenoid intermediates. It is used to demonstrate that mevalonate or one of the mevalonate phosphates is necessary for lymphocyte proliferation. |
| Molecular Formula |
C6H9FO3
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|---|---|
| Molecular Weight |
148.13
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| Exact Mass |
148.053
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| CAS # |
2822-77-7
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| PubChem CID |
119214
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| Appearance |
Colorless to light yellow oil
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
307.8±22.0 °C at 760 mmHg
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| Flash Point |
140.0±22.3 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.450
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| LogP |
-1.06
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
10
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| Complexity |
148
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=P(OC1=CC=CC=C1)(OCCCCCCCCCCCC)OC2=CC=CC=C2
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| InChi Key |
DPPMVKMESJJAJZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H9FO3/c7-4-6(9)1-2-10-5(8)3-6/h9H,1-4H2
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| Chemical Name |
4-(fluoromethyl)-4-hydroxyoxan-2-one
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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 | 6.7508 mL | 33.7541 mL | 67.5083 mL | |
| 5 mM | 1.3502 mL | 6.7508 mL | 13.5017 mL | |
| 10 mM | 0.6751 mL | 3.3754 mL | 6.7508 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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