| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
The compound targets coagulation Factor XIa (FXIa), a serine protease in the intrinsic pathway of the coagulation cascade. FXIa is activated from its zymogen precursor FXI by thrombin or FXIIa and then activates FIX, leading to thrombin generation and fibrin clot formation. Asundexian directly, effectively, and reversibly binds to the active site of FXIa, inhibiting its catalytic activity. Because the intrinsic pathway is less critical for normal hemostasis than the common and extrinsic pathways, FXIa inhibition is expected to provide antithrombotic effects without significantly increasing bleeding risk.
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| ln Vitro |
Asundexian is a potent FXIa inhibitor with an IC50 of 1 nM for human FXIa in buffer-based biochemical assays. It demonstrates high selectivity for FXIa over other coagulation proteases (e.g., thrombin, FXa, FIXa, FVIIa), which may contribute to a favorable safety profile. The compound is orally active and shows potent anticoagulant activity in in vitro assays measuring clotting time (aPTT prolongation). It is designed for once-daily dosing.
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| ln Vivo |
Asundexian has showed significant in vitro anticoagulant action in rabbit arteries and in vivo antithrombotic efficacy in a rabbit artery thrombosis model [1].
Specific in vivo data for Asundexian are not detailed in the search results, but the compound has been in clinical trials for thromboembolic diseases. FXIa inhibitors have been shown to be effective in animal models of thrombosis, including venous thrombosis (e.g., inferior vena cava ligation model) and arterial thrombosis (e.g., ferric chloride-induced carotid artery thrombosis model), with reduced bleeding compared to other anticoagulants. Asundexian would be expected to show dose-dependent antithrombotic efficacy in these models. |
| Enzyme Assay |
The FXIa enzyme activity assay is performed using a fluorogenic chromogenic substrate. Purified recombinant human FXIa is incubated with a chromogenic substrate (e.g., S-2366, pyroGlu-Pro-Arg-pNA) or a fluorogenic substrate in assay buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 5 mM CaCl2, 0.1% PEG 8000). Varying concentrations of Asundexian (0.001-1000 nM) are added, and the reaction is initiated by the addition of the substrate. The increase in absorbance (405 nm for pNA) or fluorescence (Ex/Em = 360/460 nm) is monitored continuously for 30-60 minutes at 37degC. The IC50 is calculated from the dose-response curve. Selectivity assays are performed using purified thrombin, FXa, FIXa, FVIIa, and other related proteases.
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| Cell Assay |
Cellular assays are not directly applicable for FXIa inhibitors, as FXIa acts in plasma, not within cells. Functional anticoagulant activity is assessed by measuring clotting time in plasma. Human plasma (platelet-poor or platelet-rich) is pre-incubated with varying concentrations of Asundexian (0.1-1000 nM) for 5 minutes. Clotting times are then measured using a coagulometer by adding aPTT reagent (partial thromboplastin time, a measure of the intrinsic pathway) or PT reagent (prothrombin time, a measure of the extrinsic pathway). Asundexian is expected to prolong aPTT in a concentration-dependent manner, while having minimal effect on PT, confirming its specificity for the intrinsic pathway.
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| Animal Protocol |
In vivo efficacy can be evaluated in the rabbit or rat model of venous thrombosis. Male New Zealand White rabbits are anesthetized, and a segment of the inferior vena cava (IVC) is isolated. Thrombosis is induced by a combination of venous stasis and a pro-coagulant stimulus (e.g., injection of thrombin or partial ligation of the IVC). Asundexian is administered orally at doses of 1-30 mg/kg one hour before the thrombus induction. After 60-90 minutes, the thrombus is removed and weighed. Bleeding time is assessed by a standardized incision on the ear or tail. Antithrombotic efficacy is defined as a reduction in thrombus weight, and bleeding time is used as a safety end point (FXIa inhibitors are expected to have minimal effect on bleeding).
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| ADME/Pharmacokinetics |
Asundexian is an orally active FXIa inhibitor. Specific PK parameters are not detailed in the search results, but the compound is designed for once-daily oral dosing. Key parameters expected for an oral FXIa inhibitor include good oral bioavailability (to avoid parenteral administration), a half-life suitable for once-daily dosing (e.g., 10-20 hours), and a moderate volume of distribution. Active metabolites are not expected if the compound is designed for parenteral clearance.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Asundexian are not detailed. FXIa inhibitors are expected to have a wider therapeutic window than other anticoagulants because FXI deficiency in humans (hemophilia C) is associated with a mild bleeding phenotype, primarily with trauma or surgery, but not with spontaneous bleeding. This genetic evidence supports the safety of FXIa inhibition. In animal studies, FXIa inhibitors show antithrombotic efficacy with little or no increase in bleeding time. Standard toxicological endpoints (bleeding time, thrombocytopenia, liver function) would be assessed in animal studies.
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| References | |
| Additional Infomation |
Asundexian is an investigational, clinical-stage FXIa inhibitor under development for the prevention and treatment of thromboembolic diseases, including stroke, venous thromboembolism (VTE), and myocardial infarction. Direct FXIa inhibitors represent a novel class of anticoagulants that target the intrinsic pathway, with the potential to uncouple antithrombotic efficacy from bleeding risk. Asundexian has been evaluated in Phase II clinical trials for various indications. As of the latest updates, the compound is in clinical development and has not yet been approved for sale.
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| Molecular Formula |
C26H21CLF4N6O4
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|---|---|
| Molecular Weight |
592.93
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| Exact Mass |
592.124
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| CAS # |
2064121-65-7
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| Related CAS # |
(R)-Asundexian;2064124-85-0
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| PubChem CID |
135206011
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| Appearance |
White to off-white solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
41
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| Complexity |
1080
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=C(C=CC(C(=O)N)=C1F)NC(=O)[C@@H](N1C(=O)C=C(C2C=C(Cl)C=CC=2N2N=NC(=C2)C(F)(F)F)C(OC)=C1)CC
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| InChi Key |
XYWIPYBIIRTJMM-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C26H21ClF4N6O4/c1-3-19(25(40)33-14-5-6-15(24(32)39)18(28)9-14)36-11-21(41-2)17(10-23(36)38)16-8-13(27)4-7-20(16)37-12-22(34-35-37)26(29,30)31/h4-12,19H,3H2,1-2H3,(H2,32,39)(H,33,40)/t19-/m0/s1
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| Chemical Name |
4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide
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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 (~421.63 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 | 1.6865 mL | 8.4327 mL | 16.8654 mL | |
| 5 mM | 0.3373 mL | 1.6865 mL | 3.3731 mL | |
| 10 mM | 0.1687 mL | 0.8433 mL | 1.6865 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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