| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Ranolazine-d3 targets the cardiac sodium channel (late INa current) and the potassium channel (IKr). It also inhibits fatty acid oxidation (FAO). The parent compound ranolazine achieves its anti-anginal and anti-ischemic effects primarily through inhibition of the late sodium current in cardiomyocytes, which reduces intracellular calcium overload and improves myocardial relaxation.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
In vitro, ranolazine inhibits the late sodium current (INa) with an IC50 of 6 µM and the rapid delayed rectifier potassium current (IKr) with an IC50 of 12 µM. It reduces intracellular calcium overload in cardiomyocytes. As a deuterium-labeled compound, ranolazine-d3 exhibits similar in vitro activity to the non-labeled parent compound, with the isotopic substitution primarily affecting analytical detection rather than biological activity. |
| ln Vivo |
In vivo, ranolazine has demonstrated anti-anginal and anti-ischemic effects in animal models without affecting heart rate or blood pressure. It has been shown to reduce myocardial infarct size and cardiac troponin T release in rat models. The deuterium labeling in ranolazine-d3 is not expected to significantly alter the in vivo pharmacological profile compared to the parent compound, though deuteration can potentially affect pharmacokinetic and metabolic profiles.
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| Enzyme Assay |
For non-cell-based receptor binding assays, ranolazine-d3 can be evaluated using radioligand binding displacement studies with membrane preparations from cells expressing sodium or potassium channels. Competitive binding experiments are performed with increasing concentrations of the test compound and a fixed concentration of a radiolabeled ligand specific to the channel of interest. Incubation is carried out at room temperature or 37°C for a determined period, followed by filtration through glass fiber filters to separate bound from free radioligand. Nonspecific binding is determined in the presence of excess unlabeled ligand. IC50 values are calculated from dose-response curves using nonlinear regression analysis.
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| Cell Assay |
For in vitro cellular assays, cardiomyocytes or cell lines expressing cardiac sodium channels are cultured in appropriate medium and treated with ranolazine-d3 at various concentrations. The late sodium current is measured using patch-clamp electrophysiology techniques in voltage-clamp mode. Cells are depolarized to activate sodium channels, and the late current component is measured at the end of the depolarizing pulse. Alternatively, intracellular calcium levels can be measured using fluorescent calcium indicators such as Fura-2 or Fluo-4. Cells are pre-incubated with the compound for a specified duration, and calcium influx is stimulated by depolarization or agonist application. Fluorescence intensity is recorded and compared to control untreated cells.
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| Animal Protocol |
For in vivo animal studies, ranolazine-d3 can be administered to animal models via oral gavage or intravenous injection. In rat models of myocardial ischemia, the compound is given at various doses, and infarct size is measured using triphenyltetrazolium chloride (TTC) staining following coronary artery ligation. Cardiac troponin T levels are measured in serum as a biomarker of myocardial injury. Hemodynamic parameters including heart rate and blood pressure are monitored continuously throughout the experiment. For pharmacokinetic studies, blood samples are collected at predetermined time points post-administration for LC-MS/MS analysis.
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| ADME/Pharmacokinetics |
As a deuterium-labeled compound, ranolazine-d3 is primarily used as an analytical standard rather than for therapeutic pharmacokinetic studies. Deuteration can alter the pharmacokinetic profile of drugs by affecting metabolic stability, potentially reducing the rate of metabolism and extending half-life. The parent compound ranolazine has a bioavailability of approximately 75% and is extensively metabolized in the liver. Ranolazine-d3 would be expected to have similar absorption and distribution characteristics, with the deuterium atoms potentially slowing CYP450-mediated metabolism at the labeled positions.
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| Toxicity/Toxicokinetics |
The toxicity profile of ranolazine-d3 is expected to be similar to that of the parent compound ranolazine. Ranolazine has a well-established safety profile in clinical use for angina, with common adverse effects including dizziness, nausea, and constipation. In preclinical studies, ranolazine has shown no significant genotoxicity or carcinogenicity. The deuterium substitution in ranolazine-d3 is not expected to introduce new toxicities, as deuterium is a stable, non-radioactive isotope of hydrogen that is generally considered safe for use in research and pharmaceutical applications. Standard safety pharmacology studies would include assessment of cardiovascular, respiratory, and central nervous system effects.
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| References |
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| Additional Infomation |
Ranolazine (CVT 303) is an anti-angina agent originally developed by CV Therapeutics and approved by the FDA in 2006 for the treatment of chronic stable angina. It is marketed under the brand name Ranexa and is used as add-on therapy for patients with chronic stable angina who are not adequately controlled on other anti-anginal medications. Ranolazine-d3 is the deuterium-labeled version used primarily as an internal standard in analytical method development and pharmacokinetic studies. The mechanism of action involves inhibition of the late sodium current, which reduces sodium-dependent calcium overload during ischemia.
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| Molecular Formula |
C24H30D3N3O4
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|---|---|
| Molecular Weight |
430.56
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| Exact Mass |
430.266
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| CAS # |
1054624-77-9
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| Related CAS # |
Ranolazine;95635-55-5
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| PubChem CID |
25160824
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| Appearance |
White to off-white solid powder
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| LogP |
2.833
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
31
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| Complexity |
531
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])OC1=CC=CC=C1OCC(CN2CCN(CC2)CC(=O)NC3=C(C=CC=C3C)C)O
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| InChi Key |
XKLMZUWKNUAPSZ-HPRDVNIFSA-N
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| InChi Code |
InChI=1S/C24H33N3O4/c1-18-7-6-8-19(2)24(18)25-23(29)16-27-13-11-26(12-14-27)15-20(28)17-31-22-10-5-4-9-21(22)30-3/h4-10,20,28H,11-17H2,1-3H3,(H,25,29)/i3D3
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| Chemical Name |
N-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-[2-(trideuteriomethoxy)phenoxy]propyl]piperazin-1-yl]acetamide
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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) |
DMSO: ≥ 100 mg/mL (232.26 mM)
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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 | 2.3226 mL | 11.6128 mL | 23.2256 mL | |
| 5 mM | 0.4645 mL | 2.3226 mL | 4.6451 mL | |
| 10 mM | 0.2323 mL | 1.1613 mL | 2.3226 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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