| Targets |
Acetyl-CoA is a central molecule in metabolism, acting as a substrate for the TCA cycle (citrate synthase), fatty acid synthesis (ACC), and acetylation reactions (histone acetyltransferases). The d3-labeled version targets the same enzymes but is used only as an analytical tracer; its biological activity is not exploited.
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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.
In vitro, the d3 standard is chemically identical to natural Acetyl-CoA. It is a substrate for all Acetyl-CoA-dependent enzymes. For example, in a citrate synthase assay, it converts oxaloacetate to citrate, but at trace levels used in LC-MS, it has no pharmacological effect. It is non-toxic (IC₅0 >1 mM in MTT). |
| 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.
Not administered for therapeutic purposes. It can be used in a metabolic flux study: the compound is infused into animals, and the incorporation of the label into downstream metabolites (citrate, fatty acids) is tracked by LC-MS. This is a research tool to measure metabolic pathway activity in vivo. |
| Enzyme Assay |
No direct enzyme binding assay; the compound is used as an analytical standard. For LC-MS/MS method, prepare calibration standards by spiking known amounts of unlabeled Acetyl-CoA into a surrogate matrix (e.g., charcoal-stripped plasma). Add a fixed concentration of Acetyl-CoA-d3 (e.g., 100 nM) to all samples. Extract and analyze.
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| Cell Assay |
Not performed for the d3 standard. For a cell-based metabolic assay, cells are incubated with labeled glucose or acetate, then intracellular Acetyl-CoA is extracted. The d3 standard is added during extraction to correct for loss. It is not used in viability assays.
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| Animal Protocol |
In a metabolic tracer study, mice are infused with [¹3C]glucose, and then Acetyl-CoA-d3 (0.5 mg/kg, i.v.) can be used as a spike to measure recovery. However, the standard is typically added ex vivo. For a pharmacokinetic study of an Acetyl-CoA precursor, the d3 standard is used in the bioanalysis of plasma samples.
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| ADME/Pharmacokinetics |
Acetyl-CoA is a polar, negatively charged molecule that does not cross cell membranes. It is rapidly metabolized. The d3 standard is unstable in solution and must be stored at -80degC. In plasma, it has a half-life of minutes due to degradation by plasma esterases. For analytical use, it is added after sample collection.
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| Toxicity/Toxicokinetics |
Acetyl-CoA-d3 is non-toxic and non-genotoxic at the concentrations used (nM to uM). It is an endogenous molecule. Standard laboratory handling is safe. It is not a controlled substance. For impurity qualification, it is not applicable.
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| References | |
| Additional Infomation |
Acetyl-CoA-d3 is supplied as a sodium salt, a white powder. It is stored at -80degC under an inert atmosphere. It is crucial for accurate metabolomics studies, as it allows precise quantitation of this labile metabolite. The deuterium label is stable and does not back-exchange.
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| Molecular Formula |
C23H35D3N7O17P3S
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|---|---|
| Molecular Weight |
812.59
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| CAS # |
121443-44-5
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| Related CAS # |
Acetyl coenzyme A-13C2 lithium; Acetyl coenzyme A; 72-89-9
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| Appearance |
Typically exists as solids at room temperature
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| Synonyms |
Acetyl-CoA-d3
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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 | 1.2306 mL | 6.1532 mL | 12.3063 mL | |
| 5 mM | 0.2461 mL | 1.2306 mL | 2.4613 mL | |
| 10 mM | 0.1231 mL | 0.6153 mL | 1.2306 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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