Chemical Property of Vorapaxar
Chemical Property:
- Vapor Pressure:0mmHg at 25°C
- Refractive Index:1.594
- Boiling Point:676 °C at 760 mmHg
- PKA:12.49±0.60(Predicted)
- Flash Point:362.632 °C
- PSA：77.52000
- Density:1.25 g/cm3
- LogP:6.02040
- Solubility.:≥24.65 mg/mL in DMSO; insoluble in H2O; ≥10.64 mg/mL in EtOH with ultrasonic
- XLogP3:5.3
- Hydrogen Bond Donor Count:1
- Hydrogen Bond Acceptor Count:6
- Rotatable Bond Count:6
- Exact Mass:492.24243570
- Heavy Atom Count:36
- Complexity:821
- Purity/Quality:
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99%min *data from raw suppliers
Vorapaxar >98% *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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SDS file from LookChem
Useful:
- Drug Classes:Antithrombotic Agents
- Canonical SMILES:CCOC(=O)NC1CCC2C(C1)CC3C(C2C=CC4=NC=C(C=C4)C5=CC(=CC=C5)F)C(OC3=O)C
- Isomeric SMILES:CCOC(=O)N[C@@H]1CC[C@@H]2[C@@H](C1)C[C@@H]3[C@H]([C@H]2/C=C/C4=NC=C(C=C4)C5=CC(=CC=C5)F)[C@H](OC3=O)C
- Recent ClinicalTrials:Vorapaxar on Thrombin Generation and Coagulability
- Recent EU Clinical Trials:Vorapaxar in the human endotoxemia model
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Description
Vorapaxar is a clinically approved PAR-1 antagonist for cardiovascular protection.
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Uses
Vorapaxar is a selective, reversible, potent, saturable PAR-1 antagonist and inhibits receptor-mediated effects on human platelets. FDA and EMA approved vorapaxar in 2014 to prevent thrombotic cardiovascular events in high-risk patients. Vorapaxar is a classic orthosteric antagonist that interacts with the ligand-binding site of PAR-1 and inhibits all downstream signals from this receptor.
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Mechanism of Action
In recent years, several protease-activated receptor 1 antagonists have been designed, among which Vorapaxar is a reversible Food and Drug Administration (FDA)-approved antagonist of PAR-1. Vorapaxar can effectively inhibit thrombin-mediated platelet activation, but does not reduce thrombin production or thrombin level. Vorapaxar has nearly 100% bioavailability and has been well tolerated in long-term trials of more than 40,000 atherosclerotic patients. Currently, Vorapaxar has been approved for use in previous MI and/or PAD in addition to aspirin and/or clopidogrel. Vorapaxar has been reported to be able to improve renal injury and tubulointerstitial fibrosis by inhibiting Smad signal transduction mediated by transforming growth factor-β (TGF-β). Additionally, in the experimental animal model, Vorapaxar can effectively alleviate bleomycin (BLM)-induced pulmonary fibrosis. Treatment with 2.5, 5 or 10 mg/kg Vorapaxar once a day reduced the degree of fibrosis in a dose-dependent manner. The expression of fibronectin, collagen and α smooth muscle actin decreased significantly at the messenger RNA (mRNA) and protein levels in treated mice. In vitro, our results showed that Vorapaxar could inhibit the activation of fibroblasts induced by thrombin in a dose-dependent manner. In terms of mechanism, Vorapaxar inhibits the signal transduction of JAK2/STAT1/3 by inhibiting the activation of protease activated receptor 1, which reduces the expression of HSP90β and the interaction between HSP90β and transforming growth factor-β (TGFβ) receptor II and inhibits the TGFβ/Smad signaling pathway. In conclusion, Vorapaxar inhibits the activation of pulmonary fibroblasts induced by thrombin by targeting protease activated receptor 1 and alleviates BLM-induced pulmonary fibrosis in mice.
