| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Kd: 148 nM (human platelet GP IIb/IIIa complex)[1]
Fradafiban targets the platelet glycoprotein IIb/IIIa complex (GP IIb/IIIa, also known as integrin alphaIIbbeta3). This integrin receptor is expressed on the surface of activated platelets and is the final common pathway for platelet aggregation. By binding to GP IIb/IIIa, Fradafiban competitively inhibits the binding of fibrinogen and other adhesive proteins that crosslink platelets, thereby preventing platelet aggregation and thrombus formation. |
|---|---|
| ln Vitro |
The arginine-glycine-aspartate recognition sequence is mimicked by the non-peptide mimetic frazafiban hydrochloride. Human platelet aggregation is successfully inhibited in vitro by farafiban hydrochloride, which binds to the human platelet GP IIb/IIIa complex with great affinity and selectivity. The human platelet GP IIb/IIIa complex is reversibly bound to farracafiban hydrochloride at a Kd of 148 nM [1].
In vitro, Fradafiban hydrochloride binds with high affinity and selectivity to the human platelet GP IIb/IIIa complex with a Kd of 148 nM. It potently inhibits human platelet aggregation in vitro as a reversible antagonist. The compound is a non-peptide mimetic of the RGD recognition sequence that mediates the binding of fibrinogen, von Willebrand factor, and other adhesive proteins to GP IIb/IIIa, thereby blocking platelet aggregation at the final common pathway. |
| ln Vivo |
Oral administration of farafiban hydrochloride results in poor absorption owing to its strong polarity, which likely limits its oral action [1].
In vivo, Fradafiban hydrochloride has only very limited oral activity likely due to its high polarity leading to poor absorption after oral ingestion. An orally active prodrug, Lefradafiban, was developed to overcome this limitation. Fradafiban itself is primarily used for in vitro studies of platelet aggregation inhibition, while Lefradafiban was developed for oral antithrombotic therapy. The compound was evaluated for thrombosis treatment but discontinued. |
| Enzyme Assay |
For GP IIb/IIIa binding assays, isolate human platelets from fresh blood by centrifugation. Prepare platelet membrane extracts or use purified GP IIb/IIIa protein. Incubate with 1-10 nM radiolabeled ligand (e.g., 125I-fibrinogen or 3H-Fradafiban) and varying concentrations of unlabeled Fradafiban hydrochloride (0.1 nM-10 uM) in binding buffer (50 mM Tris-HCl, 100 mM NaCl, 1 mM CaCl2, 0.5% BSA, pH 7.4) for 2 hours at 25degC. Separate bound from free by filtration through glass fiber filters and count radioactivity. Determine Kd and IC50 by nonlinear regression.
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| Cell Assay |
Culture human umbilical vein endothelial cells (HUVEC) or use freshly isolated human platelets. For platelet aggregation assays, prepare platelet-rich plasma (PRP) by centrifuging human whole blood at 200g for 10 minutes. Add Fradafiban hydrochloride (10 nM-10 uM) to PRP and incubate for 5 minutes at 37degC. Induce aggregation with agonists such as ADP (10 uM), collagen (2 ug/mL), or thrombin. Measure light transmission using a platelet aggregometer. Determine IC50 as the concentration required to inhibit maximal aggregation by 50%. Assess reversibility by washing treated platelets.
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| Animal Protocol |
For thrombosis models, use hamsters or dogs for ex vivo platelet aggregation studies following oral or intravenous administration of the prodrug Lefradafiban (Fradafiban's orally active form). To study Fradafiban itself, administer intravenously to anesthetized dogs or rats at doses of 0.1-1 mg/kg. For platelet aggregation studies, collect blood samples before and after treatment at timed intervals. Prepare PRP and measure agonist-induced aggregation ex vivo. For efficacy, use a canine coronary artery thrombosis model or ferric chloride-induced arterial thrombosis model. Assess thrombus weight and occlusion time. For bleeding time, measure tail transection bleeding time in treated vs. control animals.
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| ADME/Pharmacokinetics |
Fradafiban is a hydrophilic, non-peptide molecule with high polarity, which contributes to its poor oral bioavailability. Following intravenous administration, Fradafiban has a half-life of approximately 2-4 hours in animal models. The compound is primarily eliminated via renal excretion. The prodrug Lefradafiban is designed to have improved oral absorption and is converted to Fradafiban in vivo. DMSO solubility: 180 mg/mL (445.70 mM). Storage: 4degC, sealed, away from moisture and light; in solvent at -80degC for 6 months or -20degC for 1 month.
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| Toxicity/Toxicokinetics |
Fradafiban hydrochloride is generally well-tolerated in preclinical studies. The primary toxicity concern is bleeding due to its antiplatelet activity. At therapeutic concentrations, the risk of bleeding is elevated, as with other GP IIb/IIIa antagonists. In animal models, no severe organ toxicity was observed at doses up to 10 mg/kg. No genotoxicity or carcinogenicity data are publicly available. The compound is not intended for human consumption as a research reagent. Standard laboratory safety precautions should be used.
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| References | |
| Additional Infomation |
Fradafiban hydrochloride (BIBU-52 hydrochloride) was developed by Boehringer Ingelheim as a non-peptide GP IIb/IIIa antagonist for the treatment of thrombotic disorders. The compound's development was discontinued due to poor oral absorption. An orally active prodrug, Lefradafiban, was subsequently developed. Fradafiban is a research tool for studying platelet aggregation and GP IIb/IIIa receptor pharmacology. The compound is the subject of patent EP0486667B1.
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| Molecular Formula |
C20H22CLN3O4
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|---|---|
| Molecular Weight |
403.86
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| Related CAS # |
Fradafiban;148396-36-5
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| Appearance |
White to off-white solid powder
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
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
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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 | 2.4761 mL | 12.3805 mL | 24.7611 mL | |
| 5 mM | 0.4952 mL | 2.4761 mL | 4.9522 mL | |
| 10 mM | 0.2476 mL | 1.2381 mL | 2.4761 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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