| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg |
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| Targets |
The primary target of Darexaban is coagulation Factor Xa. It is a competitive, reversible inhibitor that binds to the active site of Factor Xa, preventing its interaction with prothrombin. Factor Xa is a serine protease that plays a pivotal role in the coagulation cascade, as one molecule of Factor Xa can generate many molecules of thrombin. By inhibiting this enzyme, Darexaban attenuates the coagulation process without directly affecting thrombin itself.
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| ln Vitro |
When taken orally, darexaban, an inhibitor of factor Xa (FXa), is quickly and thoroughly metabolized to produce its glucuronide conjugate, YM-222714. In addition to inhibiting prothrombin activation caused by the prothrombinase complex or entire blood clots with potency comparable to that of free FXa, darexaban also specifically and competitively inhibits human FXa [2].
In vitro, Darexaban demonstrates potent inhibition of Factor Xa with an IC₅₀ in the nanomolar range. It exhibits high selectivity for Factor Xa over other serine proteases such as thrombin, trypsin, and plasmin. In human plasma-based assays, it prolongs prothrombin time (PT) and activated partial thromboplastin time (aPTT) in a concentration-dependent manner. Its activity is characterized using chromogenic substrates. |
| ln Vivo |
In mice, Darexaban decreased FXa activity in plasma with an ED50 value of 24.8 mg/kg. Darexaban 3 mg/kg can extend prothrombin time (PT) [2]. In a mouse model of pulmonary thromboembolism (PE), darexaban dosage-dependently reduced mortality, with a substantial impact at a dose of 10 mg/kg [2]. In a mouse model of FeCl3-induced venous thrombosis (VT), Darexaban (0.3-10 mg/kg) dose-dependently reduced thromboprotein content, with significant effects at doses of 3 mg/kg or higher [2].
In vivo, Darexaban has been evaluated in various animal models of thrombosis, including rat and rabbit models of venous and arterial thrombosis. Oral administration resulted in dose-dependent antithrombotic efficacy with an acceptable safety profile. It showed a favorable pharmacokinetic profile with good oral bioavailability and a half-life suitable for once-daily dosing. Clinical trials were conducted, but development was later discontinued. |
| Enzyme Assay |
In vitro enzyme assays for Darexaban measure its inhibition of Factor Xa activity using a chromogenic substrate. The enzyme is incubated with various concentrations of the compound and the substrate, and the rate of chromophore release is monitored spectrophotometrically. IC₅₀ values are determined. Selectivity is assessed by testing against a panel of other serine proteases. These assays are standard for FXa inhibitors.
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| Cell Assay |
In vitro cell-based assays for Darexaban are not typical, as it acts on a plasma protein rather than a cellular target. However, its effects on platelet aggregation can be assessed in platelet-rich plasma by measuring aggregation in response to agonists. The compound's ability to reduce thrombin generation in whole blood or plasma can be measured using thrombin generation assays (calibrated automated thrombography).
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| Animal Protocol |
In vivo animal studies for Darexaban involve models of thrombosis, such as the rat vena cava ligation model or the ferric chloride-induced arterial thrombosis model. The compound is administered orally, and thrombus weight or vessel patency is assessed. Bleeding time is measured as a safety parameter. Pharmacokinetic and pharmacodynamic correlations are established. All procedures follow institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Darexaban include good oral bioavailability in preclinical species, with a half-life of several hours. It is metabolized primarily by CYP3A4 and CYP2J2. The compound is highly protein-bound. Its molecular weight is 487.55 g/mol. Storage is recommended at -20°C. Further PK details are available from published clinical trial data.
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| Toxicity/Toxicokinetics |
The toxicity profile of Darexaban was evaluated in preclinical studies; it showed a dose-dependent increase in bleeding time, which is a common side effect of anticoagulants. No significant organ toxicity was reported at therapeutic doses. However, as with all anticoagulants, there is a risk of hemorrhage. The compound was discontinued in clinical development for strategic reasons.
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| References |
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| Additional Infomation |
Darexaban has been used in numerous studies, including preventative and basic scientific research, involving Japanese, Caucasian, thromboembolic, pharmacodynamics, and pharmacokinetics. Darexaban is an orally effective inhibitor of coagulation factor Xa (activating factor X) with anticoagulant activity. Darexaban is extensively metabolized in the liver to its active metabolites and excreted via the kidneys and feces.
Additional information: Darexaban is also known as YM150. It was studied in Phase II clinical trials for the prevention of stroke in atrial fibrillation and for venous thromboembolism. Its development was halted, but it remains a research compound for studying Factor Xa inhibition. This product is for research use only and is not approved for clinical or therapeutic applications. |
| Molecular Formula |
C27H30N4O4
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|---|---|
| Molecular Weight |
474.5515
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| Exact Mass |
474.227
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| CAS # |
365462-23-3
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| PubChem CID |
9912771
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.196
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
691
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IJNIQYINMSGIPS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H30N4O4/c1-30-15-4-16-31(18-17-30)21-11-7-19(8-12-21)27(34)29-25-23(5-3-6-24(25)32)28-26(33)20-9-13-22(35-2)14-10-20/h3,5-14,32H,4,15-18H2,1-2H3,(H,28,33)(H,29,34)
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| Chemical Name |
N-[2-hydroxy-6-[(4-methoxybenzoyl)amino]phenyl]-4-(4-methyl-1,4-diazepan-1-yl)benzamide
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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 : ~250 mg/mL (~526.81 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1073 mL | 10.5363 mL | 21.0726 mL | |
| 5 mM | 0.4215 mL | 2.1073 mL | 4.2145 mL | |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1073 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 |
| NCT01405989 | Completed | Drug: darexaban Drug: ketoconazole |
Pharmacokinetics of Darexaban and Metabolites |
Astellas Pharma Inc | January 2010 | Phase 1 |
| NCT01406002 | Completed | Drug: darexaban Drug: Rifampicin |
Pharmacokinetics of Darexaban and Metabolites |
Astellas Pharma Inc | January 2010 | Phase 1 |
| NCT01514825 | Completed | Drug: YM150 Drug: Placebo |
Healthy Elderly Subject Pharmacokinetic of YM150 |
Astellas Pharma Inc | November 2006 | Phase 1 |
| NCT01424332 | Completed | Drug: Darexaban Drug: Acetyl Salicylic Acid (ASA) |
Pharmacodynamic and Pharmacokinetic Interaction |
Astellas Pharma Inc | December 2007 | Phase 1 |
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