| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Methyltransferases (enzymes that transfer methyl groups). S-adenosyl-L-methionine (SAMe) is the universal methyl donor in biological methylation reactions, transferring its methyl group to a wide range of substrates including DNA, RNA, proteins, phospholipids, and small molecules. The reaction yields S-adenosyl-L-homocysteine (SAH). SAMe is also involved in polyamine synthesis and transsulfuration pathways. (RS)-S-Adenosyl-L-methionine-d3 is used as a tracer to study these methylation dynamics in biochemical systems.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
As a deuterium-labeled tracer, (RS)-S-Adenosyl-L-methionine-d3 has nearly identical biochemical properties to the non-deuterated SAMe. SAMe is the major methyl donor in cells; its methyl group is transferred to substrates by methyltransferases. In cell-free systems, SAMe is used as a cofactor for DNA methyltransferase, histone methyltransferase, and small molecule methyltransferase assays. The d3 label allows tracking of the methyl group by mass spectrometry, enabling precise quantification of methylation reactions. |
| ln Vivo |
The parent compound S-adenosyl-L-methionine (SAMe) has in vivo activity as a metabolic cofactor. When administered exogenously, SAMe is used as a dietary supplement and has been studied as a therapeutic agent for depression, liver disease, and osteoarthritis. In animals, SAMe administration can increase global methylation status and has shown hepatoprotective effects. However, (RS)-S-Adenosyl-L-methionine-d3 is a labeled tracer intended for analytical and metabolic flux studies, not for therapeutic in vivo activity assessment.
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| Enzyme Assay |
For methyltransferase activity assays, non-cell enzyme systems are used. Recombinant DNA methyltransferase (e.g., DNMT1) or histone methyltransferase (e.g., EZH2) is incubated with substrate DNA or histone peptides, (RS)-S-Adenosyl-L-methionine-d3 (0.1-100 uM), and assay buffer at 37degC for 30-120 minutes. The reaction is quenched, and the product is analyzed by LC-MS/MS. The incorporation of deuterium-labeled methyl groups into the substrate is quantified, and kinetic parameters are calculated. The tetra-toluenesulfonate salt form improves solubility in aqueous buffers.
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| Cell Assay |
For cellular methylation studies, cells (e.g., HeLa, HEK293, or primary cells) are cultured in media supplemented with (RS)-S-Adenosyl-L-methionine-d3 (10-500 uM) for 2-48 hours. The labeled SAMe is taken up by cells and incorporated into the intracellular SAMe pool. Cells are harvested, and DNA is extracted for analysis of 5-methylcytosine by LC-MS/MS. Histones are extracted for analysis of methylated histone marks (H3K4me3, H3K9me3, H3K27me3, etc.). Small molecule metabolites are also analyzed. The d3 label allows precise quantification of methylation flux.
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| Animal Protocol |
For in vivo metabolic tracer studies, laboratory animals (typically mice or rats) are administered (RS)-S-Adenosyl-L-methionine-d3 via intravenous (IV), intraperitoneal (IP), or oral (PO) routes at doses of 10-100 mg/kg. Blood samples are collected at various time points (0-48 hours). At study termination, tissues (liver, brain, kidney, spleen) are collected. SAMe, SAH, and methylated products are extracted and analyzed by LC-MS/MS. The d3 label allows tracking of methyl group incorporation into various metabolites and measurement of methyl flux rates through metabolic pathways.
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| ADME/Pharmacokinetics |
The tetra-toluenesulfonate salt form is designed to improve the solubility and stability of the compound for use in biochemical research. For in vivo administration, the compound can be formulated in sterile saline or PBS. The deuterium label does not significantly alter the pharmacokinetics of SAMe compared to the non-labeled form. SAMe has short half-life in plasma (approximately 30-60 minutes in rodents) due to rapid metabolism. It is taken up by most tissues, with highest accumulation in the liver.
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| Toxicity/Toxicokinetics |
Deuterium is a stable, non-radioactive isotope, and the d3-labeled compound is not toxic at the concentrations used for tracer studies (typically 10-100 mg/kg in animals). The parent compound SAMe is well-tolerated and has an excellent safety profile. In clinical use as a dietary supplement, SAMe is generally well-tolerated with mild gastrointestinal side effects (nausea, diarrhea) at higher doses. No significant hepatotoxicity, nephrotoxicity, or genotoxicity has been observed. The tetra-toluenesulfonate counterion is also well-tolerated at low concentrations.
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| References | |
| Additional Infomation |
S-adenosyl-L-methionine (SAMe) is the universal methyl donor in biological systems and is essential for DNA methylation, histone methylation, neurotransmitter synthesis, and polyamine biosynthesis. The tetra-toluenesulfonate salt form (also known as ademetionine tetratosylate) is used to improve SAMe's stability and solubility. SAMe is marketed as a dietary supplement for depression, liver disease, and osteoarthritis in the US, and as a prescription drug (Ademetionine) in several countries. This deuterium-labeled version is for research use only, for studies of methylation dynamics, metabolic flux, and epigenetic regulation. It is not FDA-approved for human therapy.
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| Molecular Formula |
C43H51D3N6O17S5
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| Molecular Weight |
1090.26
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| Appearance |
Solid powder
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | 0.9172 mL | 4.5861 mL | 9.1721 mL | |
| 5 mM | 0.1834 mL | 0.9172 mL | 1.8344 mL | |
| 10 mM | 0.0917 mL | 0.4586 mL | 0.9172 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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