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.
| Original language | English |
|---|---|
| Pages (from-to) | 285-299 |
| Number of pages | 15 |
| Journal | Thrombosis and Haemostasis |
| Volume | 116 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 1 2016 |
| Externally published | Yes |
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Keywords
- Benzimidazole
- Mouse thrombotic model
- Thromboxane receptor antagonist
ASJC Scopus subject areas
- Hematology
Cite this
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.
In: Thrombosis and Haemostasis, Vol. 116, No. 2, 01.08.2016, p. 285-299.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models
AU - Huang, Shiu Wen
AU - Kuo, Heng Lan
AU - Hsu, Ming Tsung
AU - Tseng, Yufeng Jane
AU - Lin, Shu Wha
AU - Kuo, Sheng Chu
AU - Peng, Hui Chin
AU - Lien, Jin Cherng
AU - Huang, Tur Fu
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Benzimidazole
KW - Mouse thrombotic model
KW - Thromboxane receptor antagonist
UR - http://www.scopus.com/inward/record.url?scp=84980348304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84980348304&partnerID=8YFLogxK
U2 - 10.1160/TH15-12-0993
DO - 10.1160/TH15-12-0993
M3 - Article
VL - 116
SP - 285
EP - 299
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 2
ER -