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| 10mg |
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| Other Sizes |
| Targets |
IC50: 45 nM (αIIbβ3)[1]
Zalunfiban selectively targets the alphaIIbbeta3 integrin (also known as the glycoprotein IIb/IIIa receptor or GPIIb/IIIa) on the surface of platelets. It is a potent antagonist with an IC50 of 45 nM. alphaIIbbeta3 is the final common pathway for platelet aggregation, mediating cross-linking of platelets via fibrinogen binding. Zalunfiban is a non-RGD-mimetic antagonist, meaning it does not mimic the arginine-glycine-aspartate (RGD) motif. It shows selectivity for alphaIIbbeta3 over alphaVbeta3 receptors (no activity), reducing off-target effects. |
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| ln Vitro |
In vitro, Zalunfiban dihydrochloride is a potent and selective platelet alphaIIbbeta3 antagonist, with an IC50 of 45 nM. It shows no activity on alphaVbeta3 receptors, indicating selectivity. The compound blocks platelet aggregation and has potential for the treatment of acute coronary syndromes such as myocardial infarction (MI). As a non-RGD-mimetic, it may have a different binding mode and potentially reduced immunogenicity compared to RGD-based antagonists like abciximab.
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| ln Vivo |
Platelet aggregation occurs when zalunfiban dihydrochloride (1~3.86 mg/kg; sc; 24 hours) is administered[1]. High-grade suppression of platelet aggregation is initiated within 15–30 minutes by Zalunfiban dihydrochloride (1~3.86 mg/kg; im; 4.5 hours), and it lasts from ~2 to >4.5 hours in a dose-dependent manner[1].
In vivo, Zalunfiban dihydrochloride (1-3.86 mg/kg, subcutaneous) causes platelet aggregation inhibition in cynomolgus monkeys. Subcutaneous administration at 1-3.86 mg/kg results in high levels of platelet aggregation inhibition starting within 15-30 minutes, lasting for 2 to >4.5 hours in a dose-dependent manner. The compound is being studied for the treatment of myocardial infarction (MI) and has potential as a rapid-acting, reversible platelet inhibitor. |
| Enzyme Assay |
For in vitro platelet aggregation assays, human platelet-rich plasma (PRP) is prepared from freshly drawn blood anticoagulated with sodium citrate. Platelet count is adjusted to approximately 2-3 × 10^8 platelets/mL. Varying concentrations of Zalunfiban dihydrochloride (0.01-1000 nM) are pre-incubated with PRP for 1-5 minutes at 37degC. Platelet aggregation is induced by the addition of an agonist (e.g., ADP 5-20 microM, collagen 1-5 microg/mL, or thrombin 0.1-1 U/mL). Aggregation is measured using a light transmission aggregometer or by impedance in whole blood. The IC50 for inhibition of aggregation is calculated. For receptor binding assays, the affinity of Zalunfiban for alphaIIbbeta3 is measured using competitive radioligand binding. Purified alphaIIbbeta3 receptor or activated platelet membranes are incubated with [125I]-labeled RGD peptide or [3H]-labeled non-peptide antagonist in the presence of increasing concentrations of Zalunfiban (0.01-10000 nM). After incubation, bound radioligand is separated by filtration, and radioactivity is counted. The IC50 and Ki values are calculated.
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| Animal Protocol |
Animal/Disease Models: Cynomolgus Monkey
Doses: 1~ 3.86 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: Sc; 24 hrs (hours) Experimental Results: Platelet aggregation was performed. For in vivo efficacy studies in animal models of thrombosis, Zalunfiban is formulated in a suitable vehicle (e.g., PBS or saline). For ferric chloride-induced arterial thrombosis models in rats or mice, an artery (e.g., carotid or mesenteric artery) is exposed, and a filter paper soaked in FeCl3 is applied to induce vessel injury and thrombus formation. Zalunfiban is administered intravenously, subcutaneously, or intraperitoneally at doses of 0.1-10 mg/kg, either before or after injury. Blood flow is monitored by Doppler flow probe. Time to occlusion (thrombosis) or bleeding time is measured. Efficacy is determined by the prevention of occlusion or reduction in thrombus weight. Bleeding time is measured as a safety endpoint. For myocardial infarction models, coronary artery ligation is performed in rats or pigs. Zalunfiban is administered pre- or post-ligation. Infarct size is measured by triphenyltetrazolium chloride (TTC) staining. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for Zalunfiban are limited. The molecular weight of the dihydrochloride salt is 459.35, and the molecular formula is C16H20Cl2N8O2S. The compound is soluble in DMSO. For in vivo studies, it is typically formulated in saline or PBS. Following subcutaneous or intramuscular administration in cynomolgus monkeys at doses of 1-3.86 mg/kg, Zalunfiban produces rapid absorption and dose-dependent exposure. Peak platelet aggregation inhibition occurs within 15-30 minutes, and the effect lasts for 2-4.5 hours. Detailed PK parameters (t1/2, Cmax, AUC) should be obtained from primary literature.
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| Toxicity/Toxicokinetics |
Toxicological data for Zalunfiban are limited. As an alphaIIbbeta3 antagonist, the primary on-target toxicity is bleeding. In animal studies at effective antithrombotic doses, a dose-dependent increase in bleeding time is observed. No other severe toxicities have been reported. The compound's selectivity for alphaIIbbeta3 over alphaVbeta3 may reduce the risk of off-target effects. Comprehensive toxicology studies have been conducted to support clinical development.
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| References | |
| Additional Infomation |
Zalunfiban is a research compound and has been studied in preclinical models for acute myocardial infarction. It is not yet approved for clinical use. It is a potent, selective, non-RGD-mimetic alphaIIbbeta3 antagonist with an IC50 of 45 nM. Its rapid onset and reversible action make it a promising candidate for pre-hospital treatment of ST-segment elevation myocardial infarction (STEMI). The CAS number is 2815778-41-5. Store at -20degC as a powder, protected from light and moisture.
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| Molecular Formula |
C16H20CL2N8O2S
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| Molecular Weight |
459.35
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| CAS # |
2815778-41-5
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| Related CAS # |
Zalunfiban;1448313-27-6
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| Appearance |
Light yellow to green yellow 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, 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)
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| Solubility (In Vitro) |
DMSO :~6.67 mg/mL (~14.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.67 mg/mL (1.46 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 6.7 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: ≥ 0.67 mg/mL (1.46 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 6.7 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: ≥ 0.67 mg/mL (1.46 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 | 2.1770 mL | 10.8849 mL | 21.7699 mL | |
| 5 mM | 0.4354 mL | 2.1770 mL | 4.3540 mL | |
| 10 mM | 0.2177 mL | 1.0885 mL | 2.1770 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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