Thromboxane A2 synthase (TXAS) and Thromboxane A2 receptor (TBXA2R / TP receptor). Ridogrel is a dual inhibitor that both inhibits the synthesis of thromboxane A2 and blocks its receptor. Thromboxane A2 is a potent vasoconstrictor and platelet aggregator, and its inhibition reduces platelet aggregation and thrombus formation.

Rats' tail bleeding time was prolonged by R 68 070 alone (1.25 mg/kg orally, -2 hours), which was in line with TXA2 synthase inhibition (darzoxiben 10 mg/kg) and TXA2/prostaglandin. The combination of superoxide receptor blocker (BM 13177 40 mg) also had a similar effect. /Kilogram. In dogs, the chemical inhibits electrical injury-induced coronary thrombosis (1.25 mg/kg iv) and prevents occlusion/reperfusion-induced arrhythmias from evolving into ventricular fibrillation (2.5 mg/kg iv) [2.

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In vitro, Ridogrel demonstrates potent inhibition of thromboxane A2 synthase and antagonist activity at the thromboxane A2/prostaglandin endoperoxide receptor. Its dual mechanism of action provides more complete inhibition of thromboxane A2-mediated effects compared to single-target inhibitors. The compound's antiplatelet activity has been confirmed in platelet aggregation assays.

In vivo, Ridogrel has been evaluated as an adjunctive therapy with streptokinase to reduce the formation and size of blood clots. The compound's dual mechanism of action provides both inhibition of thromboxane synthesis and blockade of its receptor, offering comprehensive anti-thrombotic effects. However, there are currently no clinical indications for preferential use of Ridogrel over aspirin.

Cell-free enzyme assays for Ridogrel use purified thromboxane A2 synthase or microsomal preparations rich in the enzyme. The enzyme is incubated with its substrate (prostaglandin H2) in the presence of varying concentrations of Ridogrel (0.001-100 μM) for 15-30 minutes at 37°C. Thromboxane A2 production is measured by radioimmunoassay or ELISA for its stable metabolite (thromboxane B2). IC50 values are calculated from dose-response curves.

Cellular assays for Ridogrel use platelets isolated from human or animal blood. Platelets are pre-incubated with Ridogrel at concentrations ranging from 0.01-100 μM for 10-30 minutes, then stimulated with platelet agonists such as collagen, ADP, or arachidonic acid. Platelet aggregation is measured using a platelet aggregometer (light transmission aggregometry). Inhibition of aggregation is calculated from dose-response curves. Thromboxane B2 production in the supernatant is measured by ELISA to confirm thromboxane synthase inhibition.

In vivo efficacy studies are conducted in animal models of thrombosis, such as the ferric chloride-induced arterial thrombosis model or the arteriovenous shunt model in rats or rabbits. Ridogrel is administered orally or intravenously at doses typically ranging from 1-30 mg/kg. Thrombus formation is measured by weighing the thrombus or by assessing blood flow using Doppler ultrasound. Bleeding time is measured to assess the antiplatelet effect. In models of thrombolysis, Ridogrel is administered in combination with streptokinase to assess its adjunctive effects.

Absorption, Distribution and Excretion
Rapidly absorbed after oral administration (30-60 minutes)

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Pharmacokinetic studies of Ridogrel demonstrate that the compound is orally active. PK parameters such as Cmax, Tmax, AUC, half-life, and oral bioavailability are determined in preclinical species and in clinical studies. The compound's favorable PK properties support oral dosing for antiplatelet therapy. Metabolism and elimination pathways are characterized to assess its suitability for clinical use.

Toxicity Summary
Lidogre inhibits thromboxane A2 synthase and blocks the thromboxane A2/prostaglandin intracellular peroxidase receptor. Thrombosome synthase produces thromboxane in platelets. Thrombosome is a vasoconstrictor that promotes platelet aggregation. Therefore, by inhibiting thromboxane production and promoting its production, thrombolysis can be enhanced. Protein Binding Approximately 60% is bound to plasma proteins.

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Toxicology studies of Ridogrel were conducted as part of its clinical development program. As a thromboxane synthase inhibitor and receptor antagonist, potential toxicities may include bleeding complications and effects on vascular tone. Standard toxicology studies (acute, subchronic, and chronic) were performed in rodents and non-human primates. The compound's safety profile was evaluated in clinical trials. Specific toxicity findings are not widely reported in public sources.

[1]. R 68 070: thromboxane A2 synthetase inhibition and thromboxane A2/prostaglandin endoperoxide receptor blockade combined in one molecule--II. Pharmacological effects in vivo and ex vivo. Thromb Haemost. 1989;61(1):43-49.

[2]. Ridogrel, una nuova molecula antiaggregante piastrinica a doppio meccanismo d'azione. Profilo farmacologico e clinico [Ridogrel, a new platelet antiaggregant molecule with a double mechanism of action. A pharmacological and clinical pro.

[3]. Ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist: anti-inflammatory profile in inflammatory bowel disease. Aliment Pharmacol Ther. 2000;14(6):807-817.

Ridogrel belongs to the (trifluoromethyl)benzene family of compounds. Ridogrel is a dual-action drug used to prevent systemic thromboembolism and as adjunctive therapy in thrombolytic therapy for acute myocardial infarction. However, there is currently no clinical evidence that Ridogrel is superior to aspirin. Ridogrel has only been found in individuals who have taken the drug. It is a dual-action drug used to prevent systemic thromboembolism and as adjunctive therapy in thrombolytic therapy for acute myocardial infarction. However, there is currently no clinical evidence that Ridogrel is superior to aspirin. Ridogrel inhibits thromboxane A2 synthase and blocks the thromboxane A2/prostaglandin intraperoxide receptor. Thromboboxane synthase produces thromboxane in platelets. Thromboboxane is a vasoconstrictor that promotes platelet aggregation. Therefore, by inhibiting thromboxane production and promoting its aggregation, the thrombolytic effect can be enhanced. Drug Indications: For adjunctive treatment of patients with acute myocardial infarction to induce thrombolysis. Mechanism of Action Lidogre inhibits thromboxane A2 synthase and blocks the thromboxane A2/prostaglandin/internal peroxide receptor. Thrombosome synthase produces thromboxane in platelets. Thrombosome is a vasoconstrictor that promotes platelet aggregation. Therefore, by inhibiting and promoting thromboxane production, thrombolysis can be enhanced. Pharmacodynamics Lidogre is a combination of a thromboxane synthase inhibitor and a receptor antagonist, used in combination with streptokinase as adjunctive therapy to reduce thrombus formation and volume. Thrombi can lead to ischemic cardiac events (myocardial infarction). Lidogre has a dual action, inhibiting both thromboxane synthesis and blocking the thromboxane/prostaglandin/internal peroxide receptor. Studies have shown that Ridogrel can accelerate recanalization and delay or prevent re-occlusion during systemic thrombolytic therapy with tissue-type plasminogen activator (streptokinase). Ridogrel is a more effective antiplatelet drug than aspirin, and therefore may be more advantageous than aspirin in thrombolytic therapy for patients with acute myocardial infarction. Aspirin works by inhibiting cyclooxygenase (an enzyme responsible for thromboxane production), while Ridogrel directly inhibits thromboxane synthesis. A recent study comparing aspirin and Ridogrel as adjunctive thrombolytic agents in patients with acute myocardial infarction showed that Ridogrel was not superior to aspirin in enhancing the thrombolytic efficacy of streptokinase, but it may be more effective in preventing new ischemic events. Currently, clinical experience with this drug remains relatively limited.

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Ridogrel is a combined thromboxane synthase inhibitor and thromboxane receptor antagonist that was developed as an antiplatelet agent. It was investigated as adjunctive therapy with streptokinase for the reduction of clot formation and size. Although there are currently no clinical indications for its preferential use over aspirin, Ridogrel remains a valuable research tool for studying thromboxane-mediated platelet aggregation and thrombosis. The compound is available for research purposes.

C18H17F3N2O3

366.3344

366.119

C, 59.02; H, 4.68; F, 15.56; N, 7.65; O, 13.10

110140-89-1

5362391

White to light yellow solid powder

1.26g/cm3

495.2ºC at 760mmHg

253.3ºC

1.26E-10mmHg at 25°C

1.531

4.124

1

8

8

26

483

0

C1=CC(=CC(=C1)C(F)(F)F)/C(=N\OCCCCC(=O)O)/C2=CN=CC=C2

GLLPUTYLZIKEGF-HAVVHWLPSA-N

InChI=1S/C18H17F3N2O3/c19-18(20,21)15-7-3-5-13(11-15)17(14-6-4-9-22-12-14)23-26-10-2-1-8-16(24)25/h3-7,9,11-12H,1-2,8,10H2,(H,24,25)/b23-17+

5-[(E)-[pyridin-3-yl-[3-(trifluoromethyl)phenyl]methylidene]amino]oxypentanoic acid

R68070; R-68070; RIDOGREL; 110140-89-1; Ridogrelum; R-68,070; QTS5QOO42O; R 68070

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~100 mg/mL (~272.98 mM)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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