Thromboxane A2 synthase (TXA2 synthase) [1]

In vitro activity: Ozagrel(OKY-046) is an antiplatelet agent working as a thromboxane A2synthesis inhibitor. Ozagrel was selected as the best compound of highly selective inhibitorsof TXA2 synthase. The inhibition of TXA2 synthase by ozagrel was moreeffective on human and rabbit enzymes than those of other species.Ozagrel increased 6-keto-PGF1 alpha, one of stable metabolites of PGI2,in various isolated cells and tissues perhaps via accumulated PGendoperoxides resulted by the inhibition of TXA2 synthase

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Ozagrel prevents oleic acid (OA) induced thromboxane A(2) generation and subsequently increased total protein concentration and the numbers of macrophages and neutrophils in bronchoalveolar lavage fluid and increased monocyte chemoattractant protein-1 andinterleukin-8 mRNA expression in the whole lung of guinea pigs. Ozagrel (3 mg/kg) decreases both the area and volume of the cortical infarction after ischemia-reperfusion of the middle cerebral artery in rat. Ozagrel also has suppressive effects on the neurologic deficits in the microthrombosis rat model. Ozagrel improves the reduced spontaneously locomotor activity and the obstruction of motor coordination in the conscious cerebral ischemia-reperfusion mouse model. Ozagrel suppresses the decrease in specific gravity of the brain tissue induced by the occlusion-reperfusion in the conscious cerebral ischemia-reperfusion SHR model, and recovers the postischemic decrease in cortical PO(2) after middle cerebral artery occlusion-reperfusion in cats. Ozagrel also increases the level of 6-keto-PGF(1alpha), a metabolite of prostaglandin I(2) (PGI(2)), in the brain tissue after cerebral ischemia-reperfusion, and the administration of PGI(2) improves the reduced spontaneous locomotor activity in the conscious cerebral ischemia-reperfusion mouse model. Ozagrel administered intravenously 30 min before oleic acid injection prevents the decrease in Pao(2) and pulmonary vascular hyper-permeability in guinea-pigs. Ozagrel also prevents increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB(2) and its weight ratio to 6-keto prostaglandin F(1alpha) in bronchoalveolar lavage fluid in guinea-pigs.

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Ozagrel (80 mg/kg, intravenously, 30 min prior to OA injection) significantly decreased monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) mRNA expression in whole lungs 3 hours after OA injection. [1]
Ozagrel markedly attenuated the increase in the number of macrophages and neutrophils in bronchoalveolar lavage fluid (BALF) induced by OA. [1]
Ozagrel reduced the increase in total protein concentration in BALF (a marker of pulmonary vascular hyper-permeability) 3 hours after OA injection. [1]
Ozagrel significantly inhibited the increase in thromboxane B2 (TXB2) levels in BALF 1.5 hours after OA injection and also prevented the increase in plasma TXB2 levels. [1]
Ozagrel administered 30 minutes before OA injection prevented lung injury manifested by pulmonary vascular hyper-permeability, chemokine expression, and leukocyte accumulation. [1]

The concentration of thromboxane B2 (TXB2), a stable metabolite of TXA2, was measured using an enzyme immunoassay. For BALF samples, after bronchoalveolar lavage with ice-cold saline containing EDTA and indomethacin, the fluid was immediately centrifuged, and the supernatant was collected for the assay. For plasma samples, blood was collected and plasma separated by centrifugation, then TXB2 levels were determined by the same enzyme immunoassay. [1]

For differential leukocyte count: Cells recovered from bronchoalveolar lavage fluid (BALF) were stained with Turk's stain solution and counted using a hemocytometer. A cytospin preparation was made, and cells were stained with May-Grünwald Giemsa stain. Differential counts of macrophages, neutrophils, eosinophils, and lymphocytes were determined by light microscopy with two blinded observers and a pathologist. [1]
For chemokine mRNA expression: Total RNA was extracted from whole lung tissue using TRIzol reagent. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using an RNA PCR kit. Oligo dT-adapter primer and reverse transcriptase were used for cDNA synthesis. Specific primers were designed for MCP-1 (210 bp), IL-8 (193 bp), eotaxin (290 bp), RANTES (190 bp), and β-actin (279 bp). PCR products were separated by electrophoresis, and band intensity was semiquantified by densitometric analysis normalized against β-actin expression. [1]

3 mg/kg
Rats

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Male Hartley guinea pigs (420-500 g) were anesthetized with pentobarbital sodium. Catheters were inserted into subclavian veins for injection of reagents. Lung injury was induced by intravenous injection of 15 μL/kg oleic acid (OA). Ozagrel was administered intravenously at a dose of 80 mg/kg, 30 minutes prior to OA injection. Control animals received saline. Bronchoalveolar lavage was performed at various time points (0.75, 1.5, 3, and 6 hours after OA injection) with ice-cold saline containing EDTA and indomethacin. The lungs were then removed for RNA extraction. [1]

J Pharmacol Sci.2009 Oct;111(2):211-5;Pharmacology.1999 Nov;59(5):257-65.

Ozagrel hydrochloride is an organic molecular entity.

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Ozagrel is a rapidly acting TXA2 synthase inhibitor. The study suggests that TXA2 is a pro-inflammatory mediator that facilitates, at least partly, chemokine expression and leukocyte activation in OA-induced lung injury. Prophylactic and/or therapeutic use of rapid TXA2 synthase inhibitors like Ozagrel is proposed as a promising strategy for the prevention of ARDS/ALI, especially in patients with critical illnesses or injuries such as sepsis, trauma, and fat emboli. Further basic and clinical experiments are needed to establish efficacy. [1]

C13H12N2O2.HCL

264.71

282.077

78712-43-3

Ozagrel;82571-53-7;Ozagrel sodium;189224-26-8

6438130

White to off-white solid powder

468ºC at 760 mmHg

217 °C

236.8ºC

2.766

2

3

4

18

283

0

C1=CC(=CC=C1CN2C=CN=C2)/C=C/C(=O)O.Cl

CWKFWBJJNNPGAM-IPZCTEOASA-N

InChI=1S/C13H12N2O2.ClH/c16-13(17)6-5-11-1-3-12(4-2-11)9-15-8-7-14-10-15;/h1-8,10H,9H2,(H,16,17);1H/b6-5+;

(E)-3-[4-(imidazol-1-ylmethyl)phenyl]prop-2-enoic acid;hydrochloride

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.86 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.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.86 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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

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Solubility in Formulation 4: 25 mg/mL (94.44 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)