| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
As the active metabolite of Edoxaban, D21-2393 targets and inhibits coagulation factor Xa (FXa), a serine protease that converts prothrombin to thrombin in the coagulation cascade. By binding to the active site of FXa, D21-2393 prevents thrombin generation, thereby inhibiting fibrin clot formation. This anticoagulant effect is dose-dependent and reversible. The metabolite retains high affinity and selectivity for FXa over other serine proteases.
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| ln Vitro |
In vitro, D21-2393 is a potent inhibitor of FXa with an IC50 of 1.8 nM, which is more potent than the parent Edoxaban (IC50 = 3 nM) and another metabolite M6 (IC50 = 6.9 nM). It exhibits concentration-dependent inhibition in chromogenic substrate assays. The compound also shows reproducible matrix effects in plasma, requiring careful method validation for accurate quantification.
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| ln Vivo |
In vivo, D21-2393 contributes to the overall anticoagulant activity of Edoxaban. The metabolite is present in plasma after oral administration of Edoxaban, and its exposure correlates with the prolongation of prothrombin time and inhibition of factor Xa activity. The metabolite's half-life and area under the curve are important parameters for predicting the duration of the anticoagulant effect.
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| Enzyme Assay |
In cell-free enzymatic assays, D21-2393 activity is measured by its inhibition of FXa catalytic activity. Purified human FXa is incubated with a chromogenic substrate (e.g., S-2222) in the presence of varying concentrations of D21-2393. The hydrolysis of the substrate liberates p-nitroaniline, which is monitored at 405 nm. The IC50 is calculated from the inhibition curve. The assay is performed in 96-well plates with appropriate controls.
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| Cell Assay |
D21-2393 is not typically used in cell-based functional assays because it is a metabolite standard. However, it may be spiked into plasma or serum samples for bioanalytical method validation. Cells such as hepatocytes may be used to study the metabolism of Edoxaban to D21-2393, but the metabolite itself is primarily quantified by LC-MS/MS in biological matrices.
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| Animal Protocol |
In animal studies, D21-2393 is not administered directly; instead, it is measured as an analyte after dosing Edoxaban to rats, dogs, or monkeys. Blood samples are collected at various time points, and plasma concentrations of D21-2393 are determined by validated LC-MS/MS methods to assess metabolite exposure, pharmacokinetic parameters, and potential drug-drug interactions.
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| ADME/Pharmacokinetics |
The pharmacokinetics of D21-2393 are characterized as part of Edoxaban's overall profile. The metabolite is formed primarily via hydrolysis of the parent drug. It has a half-life similar to Edoxaban and is eliminated via renal and biliary routes. D21-2393 exhibits linear pharmacokinetics over the therapeutic dose range. Its plasma protein binding is moderate, and it is not extensively metabolized further.
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| Toxicity/Toxicokinetics |
D21-2393's toxicity is evaluated as part of the safety profile of Edoxaban. As an FXa inhibitor, the primary adverse effect is bleeding. In preclinical studies, high exposure to the metabolite was associated with increased bleeding risk. The compound is not directly administered, so its intrinsic toxicity is considered minimal. It is not mutagenic in standard genotoxicity assays.
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| References |
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| Additional Infomation |
D21-2393 is the major active metabolite of Edoxaban, also known as Edoxaban M4, with molecular formula C22H25ClN6O5S and molecular weight 521.0. It is a critical reference standard for LC-MS/MS methods in clinical pharmacology and therapeutic drug monitoring. The compound is used exclusively for research and diagnostic purposes, not as a therapeutic agent. It is supplied as a dry powder for analytical use.
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| Molecular Formula |
C22H25CLN6O5S
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|---|---|
| Molecular Weight |
520.99
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| Exact Mass |
520.129
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| CAS # |
834919-19-6
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| PubChem CID |
59676899
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.669
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| LogP |
1.7
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
836
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CN1CCC2=C(C1)SC(=N2)C(=O)N[C@@H]3C[C@H](CC[C@@H]3NC(=O)C(=O)NC4=NC=C(C=C4)Cl)C(=O)O
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| InChi Key |
QPYMJNYAASVNAP-CORIIIEPSA-N
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| InChi Code |
InChI=1S/C22H25ClN6O5S/c1-29-7-6-14-16(10-29)35-21(27-14)20(32)26-15-8-11(22(33)34)2-4-13(15)25-18(30)19(31)28-17-5-3-12(23)9-24-17/h3,5,9,11,13,15H,2,4,6-8,10H2,1H3,(H,25,30)(H,26,32)(H,33,34)(H,24,28,31)/t11-,13-,15+/m0/s1
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| Chemical Name |
(1S,3R,4S)-4-[[2-[(5-chloropyridin-2-yl)amino]-2-oxoacetyl]amino]-3-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-2-carbonyl)amino]cyclohexane-1-carboxylic acid
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| Synonyms |
UNII-IV344R972X; D21 2393; D21-2393
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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 : ~25 mg/mL (~47.99 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 | 1.9194 mL | 9.5971 mL | 19.1942 mL | |
| 5 mM | 0.3839 mL | 1.9194 mL | 3.8388 mL | |
| 10 mM | 0.1919 mL | 0.9597 mL | 1.9194 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02047565 | Completed | Drug: 60mg edoxaban | Bleeding | Daiichi Sankyo | October 2013 | Phase 1 |
| NCT01857583 | Completed | Drug: 15mg DU-176b Drug: 30mg DU-176b |
Venous Thromboembolism | Daiichi Sankyo Co., Ltd. | March 2012 | Phase 3 |
| NCT02964949 | Completed | Drug: Edoxaban | Atrial Fibrillation | Daiichi Sankyo | January 24, 2017 | Not Applicable |
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