| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Factor Xa (FXa). Betrixaban binds directly and reversibly to the active site of factor Xa with high affinity (Ki ≈ 0.1-0.5 nM). By blocking the active site of FXa, it prevents the conversion of prothrombin to thrombin, thereby inhibiting the final common pathway of the coagulation cascade. It does not require a cofactor such as antithrombin III for its antithrombotic activity. The D6 label does not alter binding affinity.
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|---|---|
| ln Vitro |
The D6-labeled compound is not used for in vitro activity assays because it serves as an internal standard. The unlabeled parent drug betrixaban inhibits factor Xa with a Ki of 0.1-0.5 nM and is at least 1000-fold selective for FXa over other serine proteases (thrombin, trypsin, plasmin, and activated protein C). In human plasma, betrixaban prolongs prothrombin time (PT) and activated partial thromboplastin time (aPTT) in a concentration-dependent manner. The D6-labeled version is chemically identical in biological activity but is distinguished by mass.
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| ln Vivo |
No in vivo activity studies have been performed with the deuterated compound. The unlabeled parent drug betrixaban is an oral, direct factor Xa inhibitor approved for the prophylaxis of venous thromboembolism (VTE) in acutely ill hospitalized medical patients. It is also investigated for stroke prevention in atrial fibrillation. It has an oral bioavailability of approximately 34% and a long terminal half-life of 35-40 hours, supporting once-daily dosing. The D6-labeled compound is not intended for in vivo use.
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| Enzyme Assay |
Not applicable, as this is a labeled internal standard for analytical chemistry, not a tool for studying enzyme binding in vitro. For the unlabeled betrixaban, factor Xa inhibition is measured in a chromogenic assay: purified human factor Xa (1 nM) is incubated with varying concentrations of betrixaban (0.01-100 nM) in 50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 0.1% PEG 8000, 0.1% BSA, and 5 mM CaCl2 for 10 minutes at 37degC. The chromogenic substrate S-2765 (200 uM) is added, and the release of p-nitroaniline is measured at 405 nm for 10-20 minutes. The inhibition constant (Ki) is calculated from the steady-state reaction rates.
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| Cell Assay |
Not applicable for the D6 compound. Betrixaban-d6 is used for method development and validation in LC-MS/MS bioanalysis rather than in cell-based assays. For cell-based assays, the unlabeled compound can be evaluated in whole blood coagulation assays, such as the rotational thromboelastometry (ROTEM) or thrombin generation assay (TGA) in human platelet-poor plasma (PPP). The D6-labeled compound itself is not used for cellular activity assessment.
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| Animal Protocol |
Not applicable. The D6-labeled compound is used as an internal standard in pharmacokinetic studies of betrixaban. In such studies, animals (rats, dogs, or non-human primates) are administered unlabeled betrixaban orally or intravenously. Blood samples are collected at multiple time points (0-72 hours), plasma is spiked with a known amount of Betrixaban D6 (e.g., 10-100 ng/mL), and the concentration of betrixaban is quantified by LC-MS/MS. The D6 compound itself is not dosed to animals. The parent drug, betrixaban, is studied in animal models of venous thrombosis and arterial thrombosis.
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| ADME/Pharmacokinetics |
Not applicable for the D6 compound. The unlabeled drug betrixaban has been extensively characterized: oral bioavailability is approximately 32-34% in humans, with a terminal half-life of 35-40 hours and a time to peak concentration (Tmax) of 2-4 hours. The volume of distribution is about 21 L, clearance is approximately 677 mL/min, and it is highly (∼90%) bound to plasma proteins, primarily albumin. It is not significantly metabolized by CYP450 enzymes but undergoes renal excretion and non-CYP hydrolysis (via gut microbiota). The D6 label does not alter PK properties.
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| Toxicity/Toxicokinetics |
No toxicity data for the D6 compound. The unlabeled drug betrixaban has a well-established safety profile based on clinical trials and its approved use. Common adverse effects include bleeding (epistaxis, hematuria, gastrointestinal hemorrhage), which is the most serious risk. Other adverse effects include headache, nausea, diarrhea, and back pain. In clinical trials, the incidence of major bleeding with betrixaban was comparable to or lower than that with enoxaparin. The deuterated compound is not expected to have an altered toxicity profile, as the label is non-radioactive and stable, posing no additional hazard.
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| References |
Nat Med.2013 Apr;19(4):446-51;Bioorg Med Chem Lett.2009 Apr 15;19(8):2179-85.
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| Additional Infomation |
Betrixaban D6 is a stable isotope-labeled internal standard for analytical chemistry applications, particularly in LC-MS/MS bioanalysis to support pharmacokinetic, toxicokinetic, and bioequivalence studies of the anticoagulant drug betrixaban. It is not a drug, has no therapeutic use, is not approved by any regulatory agency, and has never been tested in humans as a stand-alone entity. The parent drug, betrixaban, is approved by the FDA for VTE prophylaxis in acutely ill hospitalized medical patients and is marketed under the brand name Bevyxxa. The D6-labeled metabolite is sold by chemical suppliers for research use only.
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| Molecular Formula |
C23H16CLD6N5O3
|
|---|---|
| Molecular Weight |
457.95
|
| Exact Mass |
457.178
|
| CAS # |
2098655-51-5
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| Related CAS # |
Betrixaban;330942-05-7
|
| PubChem CID |
145925630
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| Appearance |
White to off-white solid powder
|
| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
32
|
| Complexity |
654
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1(=CC(=C(C=C1)NC(C1C=CC(C(N(C([2H])([2H])[2H])C([2H])([2H])[2H])=N)=CC=1)=O)C(NC1N=CC(=CC=1)Cl)=O)OC
|
| InChi Key |
PGOYJYHMBCZDLN-YJKHHXLJSA-N
|
| InChi Code |
InChI=1S/C23H22ClN5O3/c1-29(2)26-13-15-4-6-16(7-5-15)22(30)27-20-10-9-18(32-3)12-19(20)23(31)28-21-11-8-17(24)14-25-21/h4-14H,1-3H3,(H,27,30)(H,25,28,31)/b26-13+/i1D3,2D3
|
| Chemical Name |
2-[[4-[(E)-[bis(trideuteriomethyl)hydrazinylidene]methyl]benzoyl]amino]-N-(5-chloropyridin-2-yl)-5-methoxybenzamide
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| Synonyms |
Betrixaban D6PRT-054021 D6 MK4448 D6 PRT021 D6 MLN1021D6
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| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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 | 2.1836 mL | 10.9182 mL | 21.8364 mL | |
| 5 mM | 0.4367 mL | 2.1836 mL | 4.3673 mL | |
| 10 mM | 0.2184 mL | 1.0918 mL | 2.1836 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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