A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models

Shiu Wen Huang, Heng Lan Kuo, Ming Tsung Hsu, Yufeng Jane Tseng, Shu Wha Lin, Sheng Chu Kuo, Hui Chin Peng, Jin Cherng Lien, Tur Fu Huang

研究成果: 雜誌貢獻文章

8 引文 (Scopus)

摘要

A novel benzimidazole derivative, nstpbp5185, was discovered through in vitro and in vivo evaluations for antiplatelet activity. Thro-maboxane receptor (TP) is important in vascular physiology, haemostasis and pathophysiological thrombosis. Nstpbp5185 concentration-dependently inhibited human platelet aggregation caused by collagen, arachidonic acid and U46619. Nstpbp5185 caused a right-shift of the concentration-response curve of U46619 and competitively inhibited the binding of3H-SQ-29548 to TP receptor expressed on HEK-293 cells, with an IC50 of 0.1 uM, indicating that nstpbp5185 is a TP antagonist. In murine thrombosis models, nstpbp5185 significantly prolonged the latent period in triggering platelet plug formation in mesenteric and FeCl3-induced thrombi formation, and increased the survival rate in pulmonary embolism model with less bleeding than aspirin. This study suggests nstpbp5185, an orally selective antithrombotic agent, acting through blockade of TXA2 receptor, may be efficacious for prevention or treatment of pathologic thrombosis.
原文英語
頁(從 - 到)285-299
頁數15
期刊Thrombosis and Haemostasis
116
發行號2
DOIs
出版狀態已發佈 - 八月 1 2016
對外發佈Yes

指紋

Thromboxane Receptors
Platelet Aggregation
Thrombosis
Animal Models
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Fibrinolytic Agents
HEK293 Cells
Hemostasis
Pulmonary Embolism
Arachidonic Acid
Aspirin
Inhibitory Concentration 50
Blood Vessels
Collagen
Blood Platelets
Hemorrhage

ASJC Scopus subject areas

  • Hematology

引用此文

A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models. / Huang, Shiu Wen; Kuo, Heng Lan; Hsu, Ming Tsung; Tseng, Yufeng Jane; Lin, Shu Wha; Kuo, Sheng Chu; Peng, Hui Chin; Lien, Jin Cherng; Huang, Tur Fu.

於: Thrombosis and Haemostasis, 卷 116, 編號 2, 01.08.2016, p. 285-299.

研究成果: 雜誌貢獻文章

Huang, Shiu Wen ; Kuo, Heng Lan ; Hsu, Ming Tsung ; Tseng, Yufeng Jane ; Lin, Shu Wha ; Kuo, Sheng Chu ; Peng, Hui Chin ; Lien, Jin Cherng ; Huang, Tur Fu. / A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models. 於: Thrombosis and Haemostasis. 2016 ; 卷 116, 編號 2. 頁 285-299.
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abstract = "A novel benzimidazole derivative, nstpbp5185, was discovered through in vitro and in vivo evaluations for antiplatelet activity. Thro-maboxane receptor (TP) is important in vascular physiology, haemostasis and pathophysiological thrombosis. Nstpbp5185 concentration-dependently inhibited human platelet aggregation caused by collagen, arachidonic acid and U46619. Nstpbp5185 caused a right-shift of the concentration-response curve of U46619 and competitively inhibited the binding of3H-SQ-29548 to TP receptor expressed on HEK-293 cells, with an IC50 of 0.1 uM, indicating that nstpbp5185 is a TP antagonist. In murine thrombosis models, nstpbp5185 significantly prolonged the latent period in triggering platelet plug formation in mesenteric and FeCl3-induced thrombi formation, and increased the survival rate in pulmonary embolism model with less bleeding than aspirin. This study suggests nstpbp5185, an orally selective antithrombotic agent, acting through blockade of TXA2 receptor, may be efficacious for prevention or treatment of pathologic thrombosis.",
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