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| Targets |
Thromboxane A₂ (TXA₂) synthase (CYP5A1). Dazoxiben HCl is a potent, selective, and orally active inhibitor of thromboxane (TX) synthase. TXA₂ synthase is the terminal enzyme responsible for synthesizing TXA₂ from prostaglandin H₂ (PGH₂). Dazoxiben HCl is a competitive inhibitor that does not bind to TXA₂/PG-endoperoxide receptors at concentrations ≤10 μM, unlike dual-action agents such as ridogrel. By inhibiting TXA₂ synthase, Dazoxiben HCl blocks the production of TXA₂, a potent vasoconstrictor and platelet aggregator. This leads to a parallel elevation of PGE2 and other prostaglandins. The compound's mechanism of action is centered on enzyme inhibition rather than receptor antagonism.
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| ln Vitro |
During human whole blood coagulation, dazoxiben inhibits TXB2 production with an IC50 of 0.3 μM, which leads to a parallel elevation of PGE2 larger than PGF2 alpha and greater than 6-keto-PGF1 alpha production [1]. Dazoxiben interacts with PGE2, PGF2 α, and 6-keto-PGF1 α Changes are unimportant. It suppresses TXB2 synthesis in rat glomeruli (IC50 = 1.60 μM) and in rat whole blood (IC50 = 0.32 μM).
Dazoxiben HCl demonstrates potent in vitro inhibition of thromboxane synthase. It inhibits TXB₂ production in clotting human whole blood with an IC50 of 0.3 μM. The compound exhibits an in vitro IC50 of approximately 70 nM against human microsomal thromboxane synthase. By inhibiting TXA₂ synthase, Dazoxiben HCl causes a parallel elevation of PGE2 production. The compound does not bind to TXA₂/PG-endoperoxide receptors at concentrations ≤10 μM. Its selectivity for TXA₂ synthase makes it a valuable tool for studying the role of TXA₂ in platelet function and vascular biology. |
| ln Vivo |
Tail bleeding duration was dramatically extended by dazoxiben (ip; 100 μg/kg) by 96.8 ± 10.8 seconds [2].
Dazoxiben HCl has been studied in vivo for its thrombolytic effects. In a cat extracorporeal circulation model, the compound exhibited a thrombolytic ED50 of 3.8 mg/kg i.v.. As an orally active inhibitor, Dazoxiben HCl has been investigated for its potential to reduce blood clot formation. The compound reached Phase 2 clinical development. Its effects on platelet aggregation and vascular function have been evaluated in preclinical models. Detailed pharmacokinetic and pharmacodynamic data are available from preclinical and clinical studies. Dazoxiben HCl is for research use only and is not for human therapeutic use. |
| Enzyme Assay |
Thromboxane synthase enzyme activity assays are performed using human microsomal thromboxane synthase or clotting human whole blood. The enzyme is incubated with the substrate prostaglandin H₂ (PGH₂) in assay buffer. The production of TXB₂ (the stable metabolite of TXA₂) is quantified by ELISA or radioimmunoassay. Dazoxiben HCl is serially diluted in DMSO and added to the reaction mixture to determine IC50 values. The IC50 for TXB₂ production in clotting human whole blood is 0.3 μM. The IC50 against human microsomal thromboxane synthase is approximately 70 nM. Each concentration is tested in duplicate, and IC50 values are calculated by non-linear regression analysis. Appropriate positive controls and vehicle controls are included to validate the assay.
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| Cell Assay |
Cellular thromboxane synthase inhibition is evaluated in platelets or other TXA₂-producing cells. Cells are cultured in appropriate media and treated with Dazoxiben HCl at various concentrations. Thromboxane B₂ (TXB₂) production is measured by ELISA. Prostaglandin E2 (PGE2) levels are also measured to assess eicosanoid redirection. Platelet aggregation assays are performed using platelet-rich plasma (PRP) and aggregometry. Cell viability is assessed using MTT or LDH assays. Each experiment includes vehicle controls and appropriate positive controls to validate the assay systems.
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| Animal Protocol |
In vivo efficacy of Dazoxiben HCl is evaluated in animal models of thrombosis and cardiovascular disease. The compound is administered intravenously or orally at doses determined by preclinical studies. In a cat extracorporeal circulation model, Dazoxiben HCl exhibited a thrombolytic ED50 of 3.8 mg/kg i.v.. Platelet aggregation and TXB₂ levels are measured ex vivo. The compound's effects on vascular function and thrombus formation are assessed. Sample sizes typically range from 6-10 animals per group. The compound reached Phase 2 clinical development.
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| ADME/Pharmacokinetics |
Molecular Weight: 268.69 g/mol. Formula: C12H13ClN2O3. CAS No.: 74226-22-5. Synonyms: UK-37248, UK-37,248-01. Appearance: Solid powder. Solubility: Soluble in DMSO, not in water. Storage: Dry, dark, and at 0-4°C for short term or -20°C for long term. Dazoxiben HCl is an orally active, imidazole-based competitive inhibitor of thromboxane A₂ (TXA₂) synthase with an IC50 of 0.3 μM in clotting human whole blood.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available for Dazoxiben HCl. The compound is intended for research use only and has not undergone full preclinical toxicology evaluation required for clinical development. As a thromboxane synthase inhibitor, potential toxicities may include effects on platelet function and bleeding risk. Standard toxicity studies would include acute toxicity assessment in rodents, repeated dose toxicity studies (14-day and 28-day), and genotoxicity screening (Ames test, micronucleus assay). The compound is for research use only and not for human therapeutic use.
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| References |
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| Additional Infomation |
Dazoxiben HCl is also known as UK-37248, UK-37,248-01. Its IUPAC name is 4-(2-(1H-imidazol-1-yl)ethoxy)benzoic acid hydrochloride. Dazoxiben HCl is an orally active, imidazole-based competitive inhibitor of thromboxane A₂ (TXA₂) synthase (CYP5A1). It inhibits TXB₂ production in clotting human whole blood with an IC50 of 0.3 μM. The compound reached Phase 2 clinical development. No regulatory approvals have been reported. Dazoxiben HCl is for research use only.
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| Molecular Formula |
C₁₂H₁₃CLN₂O₃
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| Molecular Weight |
268.70
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| Exact Mass |
268.061
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| CAS # |
74226-22-5
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| Related CAS # |
74226-22-5 (HCl);78218-09-4;
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| PubChem CID |
53000
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| Appearance |
White to off-white solid powder
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| Boiling Point |
491.2ºC at 760 mmHg
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| Flash Point |
250.9ºC
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| LogP |
2.462
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
18
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| Complexity |
252
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.N1(CCOC2C=CC(C(O)=O)=CC=2)C=CN=C1
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| InChi Key |
PVKDFUXBDJPRGU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H12N2O3.ClH/c15-12(16)10-1-3-11(4-2-10)17-8-7-14-6-5-13-9-14/h1-6,9H,7-8H2,(H,15,16)1H
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| Chemical Name |
4-(2-(1H-Imidazol-1-yl)ethoxy)benzoic acid hydrochloride
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| Synonyms |
UK-37248 HCl UK37248 UK-37,248-01.
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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) |
H2O : ≥ 100 mg/mL (~372.16 mM)
DMSO : ~25 mg/mL (~93.04 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.74 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 20.8 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: ≥ 2.08 mg/mL (7.74 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 20.8 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: ≥ 2.08 mg/mL (7.74 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 | 3.7216 mL | 18.6081 mL | 37.2162 mL | |
| 5 mM | 0.7443 mL | 3.7216 mL | 7.4432 mL | |
| 10 mM | 0.3722 mL | 1.8608 mL | 3.7216 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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