| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
The primary molecular target of Otamixaban is coagulation factor Xa (fXa), a key serine protease in the blood coagulation cascade. fXa plays a central role in the conversion of prothrombin to thrombin, which is a critical step in the formation of a blood clot. By inhibiting fXa, Otamixaban effectively reduces the generation of thrombin, thereby preventing the formation of fibrin clots and inhibiting platelet aggregation. Its high selectivity for fXa over other proteases is a key feature that minimizes off-target effects and contributes to its favorable safety profile.
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| ln Vitro |
In vitro, Otamixaban is a highly potent inhibitor of factor Xa. Its inhibitory constant (Ki) is 0.5 nM, indicating extremely high affinity for the enzyme. It is a competitive inhibitor, meaning it binds to the active site of fXa and prevents the enzyme from interacting with its natural substrate, prothrombin. Furthermore, it is a reversible inhibitor, which allows for the rapid restoration of coagulation function upon drug clearance. Its activity against both free and prothrombinase-bound fXa is a significant advantage, as it ensures efficacy even in the context of an assembled prothrombinase complex, which is the physiologically relevant form of the enzyme.
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| ln Vivo |
In vivo, Otamixaban has demonstrated high efficacy as an antithrombotic agent in several animal models, including rodent, canine, and porcine models of thrombosis. Its rapid onset of action makes it particularly suitable for acute indications, such as acute coronary syndrome (ACS). Clinical studies have shown that Otamixaban is efficacious, safe, and well-tolerated in humans, highlighting its considerable potential for the treatment of thrombotic disorders. The compound's efficacy is directly linked to its ability to inhibit fXa and reduce thrombin generation in vivo.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, the activity of Otamixaban is assessed by measuring its inhibition of factor Xa. Standard protocols involve incubating purified human fXa with a chromogenic or fluorogenic substrate in the presence of varying concentrations of the inhibitor. The substrate is cleaved by fXa, releasing a detectable signal. The decrease in signal in the presence of Otamixaban is used to calculate the inhibition constant (Ki). These assays can be performed in the presence of prothrombinase complex components to evaluate its activity against the physiologically relevant form of the enzyme. Its selectivity is confirmed by testing against a panel of other serine proteases.
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| Cell Assay |
Cell-based in vitro assays for Otamixaban are not typically performed, as its mechanism of action is extracellular, involving the inhibition of a circulating coagulation factor. However, its activity can be assessed in plasma-based assays. For example, prothrombin time (PT) and activated partial thromboplastin time (aPTT) can be measured in human plasma spiked with Otamixaban. The prolongation of these clotting times is a functional measure of its anticoagulant activity. These assays are crucial for translating in vitro enzyme inhibition to a functional anticoagulant effect.
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| Animal Protocol |
In vivo animal experiments for Otamixaban are performed in various thrombosis models. In these studies, thrombosis is induced in animals (e.g., by vascular injury or by the injection of thrombogenic agents), and the compound is administered intravenously or orally. The primary endpoints include the reduction in thrombus formation, the prevention of vessel occlusion, and the effect on bleeding time. Its efficacy has been demonstrated in rodent, canine, and porcine models, confirming its broad-spectrum antithrombotic activity.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of Otamixaban have been characterized in preclinical and clinical studies. The compound is known for its rapid onset of action, which is a key feature for an acute care drug. Its PK profile likely includes a short half-life, allowing for rapid clearance and tight control of its anticoagulant effect. It is likely administered intravenously for acute indications. Specific parameters such as bioavailability, volume of distribution, and clearance would be established in clinical trials. Its reversible nature is an important PK property, as it allows for the rapid return of normal coagulation function.
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| Toxicity/Toxicokinetics |
Toxicology data for Otamixaban are derived from preclinical safety studies and clinical trials. As an anticoagulant, the primary safety concern is bleeding. However, clinical findings indicate that it is well-tolerated in humans, suggesting a manageable safety profile. Its high selectivity for fXa over other proteases is likely a contributing factor to its reduced off-target toxicity. Preclinical studies would have assessed its acute and chronic toxicity, genotoxicity, and reproductive toxicity.
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| References |
Anticoagulation therapy: Otamixaban fails in NSTE-ACS. Nat Rev Cardiol. 2013 Nov;10(11):615.
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| Additional Infomation |
Otamixaban is a novel direct factor Xa (FXa) inhibitor. Currently, the French pharmaceutical company Sanofi-Aventis is developing this drug for the treatment of acute coronary syndromes. Otamixaban is a factor Xa (activating factor X) inhibitor with anticoagulant activity. Otamixaban has a short half-life, ranging from 1.5 to 3 hours. Drug Indications It has been studied for the treatment of thrombosis.
In summary, Otamixaban (FXV-673) is a potent, selective, and rapid-acting direct inhibitor of factor Xa. It has a Ki of 0.5 nM and is highly selective for fXa over other serine proteases. Its efficacy has been demonstrated in various animal models of thrombosis and in clinical trials for acute coronary syndrome. The compound is a valuable tool for studying coagulation and has considerable potential for therapeutic use. It is available for research purposes and has undergone clinical investigation. |
| Molecular Formula |
C25H26N4O4
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|---|---|
| Molecular Weight |
C25H26N4O4
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| Exact Mass |
446.195
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| CAS # |
193153-04-7
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| Related CAS # |
409081-12-5 (HCl); 193153-04-7;
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| PubChem CID |
5496659
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.619
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| LogP |
0.58
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
33
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| Complexity |
671
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]([C@@H](CC1=CC(=CC=C1)C(=N)N)C(=O)OC)NC(=O)C2=CC=C(C=C2)C3=CC=[N+](C=C3)[O-]
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| InChi Key |
PFGVNLZDWRZPJW-OPAMFIHVSA-N
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| InChi Code |
InChI=1S/C25H26N4O4/c1-16(22(25(31)33-2)15-17-4-3-5-21(14-17)23(26)27)28-24(30)20-8-6-18(7-9-20)19-10-12-29(32)13-11-19/h3-14,16,22H,15H2,1-2H3,(H3,26,27)(H,28,30)/t16-,22-/m1/s1
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| Chemical Name |
Methyl (2R,3R)-2-(3-carbamimidoylbenzyl)-3-((4-(1-oxidopyridin-4-yl)benzoyl)amino)butanoate
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| Synonyms |
XRP673 XRP0673XRP-673 XRP-0673XRP 673 XRP 0673
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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 : ~50 mg/mL (~111.98 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.16 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 27.5 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: ≥ 2.75 mg/mL (6.16 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 27.5 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: ≥ 2.75 mg/mL (6.16 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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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