| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
4-Methoxyestradiol-d5 has no therapeutic target. The unlabeled parent compound, 4-Methoxyestradiol (4-MeOE2), has been reported to induce oxidative DNA damage in human lung epithelial cells (H1355). It increases the production of reactive oxygen species (ROS) and upregulates superoxide dismutase (SOD) activity. It is also a methoxy estrogen metabolite. The parent hormone, 17beta-estradiol, exerts its effects by binding to nuclear estrogen receptors (ERalpha and ERbeta). As a methoxylated derivative, 4-Methoxyestradiol has lower affinity for ERs and is considered a genotoxic metabolite. The labeled standard is used for quantification.
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| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools.
4-Methoxyestradiol-d5 itself is not biologically active. The unlabeled 4-Methoxyestradiol induces oxidative DNA damage in human lung epithelial cells (H1355) in vitro. It increases the levels of 8-oxo-dG (a marker of DNA damage) in a concentration-dependent manner. It also increases the activities of reactive oxygen species (ROS) and superoxide dismutase (SOD) in these cells. In contrast, the labeled d5 internal standard is chemically identical but is only used in LC-MS assays. It has the same chemical stability and solubility. |
| ln Vivo |
Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
4-Methoxyestradiol-d5 is not administered in vivo. The unlabeled metabolite, 4-Methoxyestradiol, is a natural endogenous metabolite of estrogen that circulates in the blood and is excreted in the urine. Its concentration is used as a biomarker for certain cancers (e.g., breast cancer) and for assessing estrogen metabolism pathways. The stable isotope-labeled form is used as an internal standard to improve the accuracy of these quantitative measurements. It corrects for the loss of the analyte during the sample preparation process. |
| Enzyme Assay |
4-Methoxyestradiol-d5 is an analytical standard, not a substrate for enzyme assays. For the quantification of 4-Methoxyestradiol in urine, an LC-MS/MS method is used. Human urine (0.5 mL) is spiked with 10 uL of 4-Methoxyestradiol-d5 (100 ng/mL). The sample is hydrolyzed with beta-glucuronidase (50 U/mL) in 0.1 M acetate buffer (pH 5.0) at 37degC for 2 h. The sample is then extracted by liquid-liquid extraction (ethyl acetate). The extract is injected onto a C18 reverse-phase column (2.1 × 100 mm, 1.7 um). A gradient mobile phase of water/acetonitrile with 0.1% formic acid is used. Detection is performed in negative ion mode using multiple reaction monitoring (MRM) transition m/z 303 → 269 (for 4-Methoxyestradiol) and m/z 308 → 274 (for the d5 internal standard).
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| Cell Assay |
4-Methoxyestradiol-d5 is not used in cell-based assays. For toxicity screening, HepG2 or HEK293 cells are seeded in 96-well plates (1×10⁴ cells/well) and treated with 4-Methoxyestradiol-d5 (1-1000 uM) for 24-72 h. Cell viability is measured by MTT assay. The CC₅0 is expected to be > 100 uM, indicating moderate cytotoxicity. The unlabeled compound (4-MeOE2) is used to induce DNA damage in H1355 cells. Cells are treated with the unlabeled compound (1-10 uM) for 24 h, and the presence of 8-oxo-dG is measured by immunofluorescence or HPLC-ECD. The labeled standard is not used in these studies.
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| Animal Protocol |
No in vivo animal protocol for 4-Methoxyestradiol-d5 exists. For pharmacokinetic studies of estrogen metabolites, female Sprague-Dawley rats (200-250 g, n=6/group) are administered 17beta-estradiol (0.5-2 mg/kg) subcutaneously. Blood samples are collected at various time points. 4-Methoxyestradiol-d5 is added to the plasma samples as an internal standard before extraction. The concentration of 4-Methoxyestradiol in plasma is quantified by LC-MS/MS. The pharmacokinetic parameters (Cmax, Tmax, AUC, t½) of the endogenous metabolite are calculated. This standard is used for bioanalytical method validation.
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| ADME/Pharmacokinetics |
4-Methoxyestradiol-d5 is not a drug. It is an analytical standard. It has the same molecular weight (307.44) as the unlabeled compound (302.41), with an increase of 5 Da due to the 5 deuterium atoms. It is supplied as a solid powder. The compound is stable at -20degC for several years. It is soluble in DMSO and ethanol. The isotope purity is > 99%. The compound is not intended for in vivo use. It is a research reagent for LC-MS method development.
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| Toxicity/Toxicokinetics |
For 4-Methoxyestradiol-d5, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: powder at -20degC, 4degC for 2 years; in solvent at -80degC for 6 months, -20degC for 1 month. Protect from light.
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| References | |
| Additional Infomation |
4-Methoxyestradiol-d5 (CAS# 1246818-62-5) is a research-grade stable isotope-labeled internal standard. It is not an FDA-approved drug. It is used for the quantification of the estrogen metabolite 4-Methoxyestradiol in biological matrices by LC-MS/MS for biomarker discovery in cancer and metabolic disorders. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C19H21D5O3
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|---|---|
| Molecular Weight |
307.44
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| Related CAS # |
4-Methoxyestradiol; 26788-23-8
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| Appearance |
Typically exists as solids at room temperature
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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 | 3.2527 mL | 16.2633 mL | 32.5267 mL | |
| 5 mM | 0.6505 mL | 3.2527 mL | 6.5053 mL | |
| 10 mM | 0.3253 mL | 1.6263 mL | 3.2527 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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