| Size | Price | |
|---|---|---|
| 1mg | ||
| 5mg | ||
| Other Sizes |
| Targets |
Target: Thrombin (direct competitive inhibitor). Dabigatran-d4 shares the same mechanism as its unlabeled parent; Ki against human thrombin is 4.5 nM. It also inhibits thrombin-induced platelet aggregation with an IC50 of 10 nM. No specific isotope effect alterations to target engagement are expected under normal analytical usage conditions.
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| ln Vitro |
In vitro, dabigatran (BIBR 953) concentration-dependently inhibits the activity of soluble thrombin and thrombin-mediated fibrin clot formation. It blocks thrombin-induced platelet aggregation with an IC50 of 10 nM. The compound demonstrates high selectivity for thrombin over other trypsin-like serine proteases. These properties are retained by the deuterium-labeled version, though the d4 compound itself is primarily used as an analytical standard rather than for primary activity profiling.
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| ln Vivo |
In vivo, dabigatran (the parent molecule) exhibits potent anticoagulant effects with a rapid onset of action. After oral administration of dabigatran etexilate prodrug, peak plasma concentrations of active dabigatran are achieved within 0.5-2.0 hours. The direct thrombin inhibitor has proven effective in primary and secondary stroke prevention in nonvalvular atrial fibrillation patients. In various animal models, dabigatran produces dose-dependent prolongation of clotting parameters such as thrombin time (TT), ecarin clotting time (ECT), and activated partial thromboplastin time (aPTT).
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| Enzyme Assay |
For receptor binding assays, the unlabeled dabigatran is typically used. The direct inhibition is evaluated using chromogenic substrate-based assays. Specifically, various concentrations of the inhibitor are pre-incubated with human alpha-thrombin (e.g., 1 nM) in assay buffer (50 mM Tris-HCl, pH 7.4, containing 150 mM NaCl, 0.1% PEG 6000) for 5-10 minutes. A chromogenic substrate (e.g., S-2238; 50-200 microM) is then added, and residual thrombin activity is measured by monitoring absorbance at 405 nm. The inhibition constant Ki is determined by fitting the data to a competitive inhibition model.
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| Cell Assay |
Standard in vitro cellular assays for dabigatran-d4 are not commonly established as its primary role is analytical. As an internal standard for LC-MS/MS workflows, the general protocol involves spiking a stable isotope-labeled internal standard into biological matrices (plasma, urine, tissue homogenates) containing the analyte of interest. After sample preparation (protein precipitation with acetonitrile, liquid-liquid extraction, or solid-phase extraction), the reconstituted samples are analyzed by LC-MS/MS, quantifying the analyte against the fixed concentration of d4 standard to correct for matrix effects and extraction efficiency.
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| Animal Protocol |
For the unlabeled parent drug, efficacy in animal thrombosis models (e.g., rat venous stasis model or rabbit jugular vein model) is assessed. A typical protocol involves orally administering dabigatran etexilate to male rats at doses ranging from 1-10 mg/kg, followed by induction of venous thrombosis via ligation. After 15-60 minutes, the formed thrombus is weighed. Plasma samples are collected at various time points for drug concentration analysis, and anticoagulant biomarkers (aPTT, ECT, TT) are measured to establish PK/PD relationships.
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| ADME/Pharmacokinetics |
As a deuterated internal standard, dabigatran-d4 is intended to mimic the physicochemical and chromatographic behavior of dabigatran. Pharmacokinetic parameters of the unlabeled parent in humans: After intravenous administration of 5 mg, Cmax is approximately 293 ng/mL (coefficient of variation ~28%), with a clearance of 2.3-3.1 L/h and a terminal half-life of 7-9 hours. Following oral administration of 300 mg as the prodrug, absolute bioavailability is ~6.5% due to incomplete absorption. The parent drug dabigatran exhibits low plasma protein binding (~35%) and is primarily excreted unchanged in urine (approximately 80%).
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| Toxicity/Toxicokinetics |
Dabigatran-d4 is a stable isotopologue and poses minimal toxicological risk at its intended analytical usage level (pg/mL to ng/mL range), far below any pharmacologically active concentrations. The unlabeled parent drug dabigatran has an acceptable safety profile in patients, with the most significant adverse events being bleeding complications, including gastrointestinal hemorrhage and intracranial hemorrhage. Other potential adverse effects include dyspepsia, gastritis-like symptoms, and abnormal hepatic function.
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| Additional Infomation |
Dabigatran itself is a direct thrombin inhibitor. Its prodrug, dabigatran etexilate (BIBR 1048), is orally administered and hydrolyzed by carboxylesterases to the active dabigatran. The active form reversibly binds to the active site of thrombin, inhibiting fibrinogen cleavage and platelet activation. Dabigatran is not metabolized by CYP450 isozymes, thus exhibiting low potential for drug-drug interactions. It has received widespread approval for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation, treatment of deep vein thrombosis and pulmonary embolism, and prophylaxis of venous thromboembolism following major orthopedic surgery. Dabigatran-d4 is strictly for research use only.
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| Molecular Formula |
C25H22D4CLN7O3
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|---|---|
| Molecular Weight |
512.00
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| Related CAS # |
Dabigatran;211914-51-1;Dabigatran etexilate;211915-06-9;Dabigatran etexilate mesylate;872728-81-9;Dabigatran (ethyl ester);429658-95-7;Dabigatran-d4;1618637-32-3
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| Appearance |
Typically exists as solid 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 | 1.9531 mL | 9.7656 mL | 19.5312 mL | |
| 5 mM | 0.3906 mL | 1.9531 mL | 3.9062 mL | |
| 10 mM | 0.1953 mL | 0.9766 mL | 1.9531 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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