Protease-Activated Receptor Antagonist for Reducing Cardiovascular Events – A Review on Vorapaxar

Gupta, Rahul; Lin, Muling; Mehta, Anila; Aedma, Surya Kiran; Shah, Rita; Ranchal, Purva; Vyas, Apurva; Singh, Shailendra; Kluck, Bryan; Combs, William; Patel, Nainesh C

doi:10.1016/j.cpcardiol.2021.101035

Cited by 6 publications

(2 citation statements)

References 35 publications

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“…By inhibiting thrombin activity, the pathological process of atherosclerosis can be improved, and the risk of cardiovascular events can be reduced [14]. Thrombin is a serine protease that can hydrolyze various substrates, such as coagulation factors, fibrinolytic system factors, complement system factors, growth factors, and so on [15].…”

Section: Discovery and Characterization Of Panaxatriol As A Novel Thr...mentioning

confidence: 99%

Discovery and Characterization of Panaxatriol as a Novel Thrombin Inhibitor from Panax notoginseng Using a Combination of Computational and Experimental Approaches

Wang,

Ma,

Zuo

et al. 2024

Planta Med

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Thrombin is a crucial enzyme in the coagulation cascade, and inhibitors of thrombin have been extensively studied as potential antithrombotic agents. The objective of this study was to identify natural inhibitors of thrombin from Panax notoginseng and evaluate their biological activity in vitro and binding characteristics. A combined approach involving molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation was utilized to identify natural thrombin inhibitors. The results demonstrated that that panaxatriol directly inhibits thrombin with an IC50 of 10.3 μM. Binding studies using SPR revealed that panaxatriol interacts with thrombin with a KD value of 7.8 μM. Molecular dynamics analysis indicated that the thrombin-panaxatriol system reached equilibrium rapidly with minimal fluctuations, and the calculated binding free energy was -23.8 kcal/mol. The interaction between panaxatriol and thrombin involves the amino acid residues Glu146, Glu192, Gly216, Gly219, Tyr60A, and Trp60D. This interaction provides a mechanistic basis for further optimizing panaxatriol as a thrombin inhibitor. Our study has shown that panaxatriol serves as a direct thrombin inhibitor, laying the groundwork for further research and development of novel thrombin inhibitor.

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Section: Discovery and Characterization Of Panaxatriol As A Novel Thr...mentioning

confidence: 99%

Discovery and Characterization of Panaxatriol as a Novel Thrombin Inhibitor from Panax notoginseng Using a Combination of Computational and Experimental Approaches

Wang,

Ma,

Zuo

et al. 2024

Planta Med

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“…PAR-1 can be activated by thrombin to regulate platelet aggregation and endothelial permeability, so it is clinically used as a target for anti-platelet drugs to prevent thrombosis (125)(126)(127). Vorapaxar is a representative drug (128). IR induction was performed in rat lung models by perfusion in vitro.…”

Section: The Par-1 Antagonistmentioning

confidence: 99%

Research progress of NF-κB signaling pathway and thrombosis

Wang,

Fang,

Yao

et al. 2023

Front. Immunol.

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Venous thromboembolism is a very common and costly health problem. Deep-vein thrombosis (DVT) can cause permanent damage to the venous system and lead to swelling, ulceration, gangrene, and other symptoms in the affected limb. In addition, more than half of the embolus of pulmonary embolism comes from venous thrombosis, which is the most serious cause of death, second only to ischemic heart disease and stroke patients. It can be seen that deep-vein thrombosis has become a serious disease affecting human health. In recent years, with the deepening of research, inflammatory response is considered to be an important pathway to trigger venous thromboembolism, in which the transcription factor NF-κB is the central medium of inflammation, and the NF-κB signaling pathway can regulate the pro-inflammatory and coagulation response. Thus, to explore the mechanism and make use of it may provide new solutions for the prevention and treatment of thrombosis.

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