| Size | Price | |
|---|---|---|
| 5mg | ||
| 10mg | ||
| 50mg | ||
| Other Sizes |
| Targets |
IC50: Factor Xa[1]
Factor Xa (FXa). Otamixaban is a direct and selective inhibitor of the active site of FXa, a key serine protease in the coagulation cascade. By binding to FXa, it blocks the conversion of prothrombin to thrombin, thereby reducing fibrin generation and platelet activation. |
|---|---|
| ln Vitro |
Otamixaban is a potent inhibitor of human Factor Xa in cell-free enzyme assays. It demonstrates excellent selectivity for FXa over other serine proteases in the coagulation pathway. This high potency translates into strong ex vivo anticoagulant activity, as confirmed by the prolongation of clotting times in human plasma samples.
|
| ln Vivo |
In a Phase 2 clinical trial (SEPIA-ACS1 TIMI 42), otamixaban significantly reduced the levels of the coagulation activation marker prothrombin fragment 1+2 (F1+2) compared to unfractionated heparin (UFH). The primary efficacy composite outcome showed a 42% relative risk reduction (RRR) with the highest infusion doses. Efficacy was also confirmed in a rat model of venous thrombosis.
|
| Enzyme Assay |
A standard assay involves incubating human Factor Xa (FXa) with a chromogenic substrate in 96-well plates. Varying concentrations of Otamixaban are added to the reaction mixture containing buffer (e.g., Tris-HCl, pH 7.4, 150 mM NaCl). The reaction is initiated by adding the substrate. The rate of pNA release is measured at 405 nm, and the IC50 is calculated from the resulting inhibition curve to confirm direct target engagement.
|
| Cell Assay |
For anticoagulation efficacy assays, human platelet-poor plasma (PPP) is spiked with Otamixaban at clinically relevant concentrations. Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) are measured using a coagulometer. The prolongation of these clotting times serves as a functional readout of FXa inhibition in a biological matrix, confirming the drug's effect on the coagulation cascade.
|
| Animal Protocol |
Animal efficacy studies involved intravenous administration of otamixaban in rat models of venous thrombosis or arterio-venous shunt thrombosis. The primary endpoint was thrombus weight reduction. For PK/PD correlation, serial blood samples were collected to measure plasma drug concentration (via LC-MS/MS) and ex vivo clotting times (e.g., aPTT and PT).
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| ADME/Pharmacokinetics |
Pharmacokinetic analysis in animal models and humans confirmed that otamixaban has a fast onset and offset of action following intravenous administration, as expected for a short-acting, reversible direct FXa inhibitor. The half-life is short (approximately 1-2 hours in humans). It displayed linear pharmacokinetics, making it suitable for weight-adjusted, continuous intravenous infusion.
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| Toxicity/Toxicokinetics |
Toxicological data are derived from the terminated clinical trial. While the drug demonstrated potent anticoagulant effects, it was associated with a significantly higher rate of bleeding compared to the control group. The Phase III trial (SEPIA-ACS1 TIMI 42) showed that bleeding events requiring discontinuation of the study drug were 4.7% in the otamixaban group versus 1.7% in the UFH-plus-epitfibatide group (p < 0.001).
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| References | |
| Additional Infomation |
Otamixaban was developed by Sanofi. It completed Phase II trials with promising efficacy signals, but development was discontinued in 2013 following poor performance in a Phase III trial for acute coronary syndrome. It represents a potent, direct FXa inhibitor whose clinical development was hindered by its bleeding risk. Its mechanism is similar to that of approved oral anticoagulants like apixaban and rivaroxaban.
|
| Molecular Formula |
C25H27CLN4O4
|
|---|---|
| Molecular Weight |
482.96
|
| Exact Mass |
482.172
|
| CAS # |
409081-12-5
|
| PubChem CID |
50899073
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
5.209
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
34
|
| Complexity |
671
|
| Defined Atom Stereocenter Count |
2
|
| 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-].Cl
|
| InChi Key |
ROKCPUOLRIBSQQ-BYYQELCVSA-N
|
| InChi Code |
InChI=1S/C25H26N4O4.ClH/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);1H/t16-,22-;/m1./s1
|
| Chemical Name |
methyl (2R,3R)-2-[(3-carbamimidoylphenyl)methyl]-3-[[4-(1-oxidopyridin-1-ium-4-yl)benzoyl]amino]butanoate;hydrochloride
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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
|
|---|---|
| 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 | 2.0706 mL | 10.3528 mL | 20.7056 mL | |
| 5 mM | 0.4141 mL | 2.0706 mL | 4.1411 mL | |
| 10 mM | 0.2071 mL | 1.0353 mL | 2.0706 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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