RPR120844, a Novel, Specific Inhibitor of Coagulation Factor Xa Inhibits Venous Thrombosis in the Rabbit

Bostwick, Jeffery; Bentley, Ross; Morgan, Susan; Brown, Karen; Chu, Valeria; Ewing, William R.; Spada, Alfred P.; Pauls, Henry W.; Perrone, Mark H.; Dunwiddie, Christopher T.; Leadley, Robert J.

doi:10.1055/s-0037-1614434

Cited by 18 publications

(1 citation statement)

References 13 publications

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“…Orally active pyrazole DPC423 attenuates electrically induced carotid artery thrombosis in rabbits (140). Isoxazolines and isoxazoles prevent A-V shuntthrombosis (141), while RPR120844 reduces venous thrombosis in rabbits (142).…”

Section: Anti-fxamentioning

confidence: 99%

Role of Tissue Factor in Thrombosis. Coagulation-Inflammation-Thrombosis circuit

Chu¹

2006

Front Biosci

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Tissue factor (TF) plays a role in thrombogenesis. TF initiates blood coagulation resulting in the generation of protease coagulant mediators (FVIIa, FXa, and FIIa) and fibrin production. TF hypercoagulablility directly contributes to thrombus formation resulting from the major events of fibrin deposition and FIIa-induced platelet activation/aggregation. In addition, blood coagulation indirectly promotes thrombogenicity via the coagulation-inflammation cycle in which TF plays a diverging and converging role. As the consequence of coagulation-dependent inflammation in which protease-activated receptor (PAR) mediates the coagulant signaling to elicit cytokines, selectins, and growth factors, such inflammation facilitates thrombosis by platelet aggregation and leukocyte recruitment. As TF hypercoagulability concerned, anti-thrombotic strategies involve the prevention by anticoagulation and PAR antagonism. Anticoagulants block the direct and indirect thrombotic contributions, while PAR antagonists arrest coagulation-dependent inflammation. With respect to both thrombosis and inflammation being cardiovascular risk factors, such strategies offer diverse benefits to cardioprotection.

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Section: Anti-fxamentioning

confidence: 99%

Role of Tissue Factor in Thrombosis. Coagulation-Inflammation-Thrombosis circuit

Chu¹

2006

Front Biosci

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Antithrombotic effects of YM466, a synthesized direct inhibitor of factor Xa, in an arterio‐venous shunt thrombosis model in squirrel monkeys

Iwatsuki¹,

Kaku²,

Moritani³

et al. 2003

Drug Development Research

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The antithrombotic effects of YM466, a synthetic direct inhibitor of human factor Xa (FXa), were evaluated in an arterio-venous shunt thrombosis model in squirrel monkeys. YM466 significantly inhibited thrombus formation after continuous IV zx infusion at doses of 3-30 mg/kg/h. Although prothrombin time (PT) was significantly prolonged at doses of 10 and 30 mg/kg/h, this effect was small (1.2-and 1.4-fold of the control, respectively). Furthermore, YM466 had no effect on template bleeding time and activated partial thromboplastin time at any dose. Plasma anti-FXa activity increased in a dosedependent manner correlating with the antithrombotic effect of YM466. Thrombin-antithrombin III complex levels decreased to less than normal levels at 30 mg/kg/h of YM466. Mean plasma concentrations of YM466 measured by LC/MS/MS were 2.5, 10.5, 27.4, and 75.5 ng/ml at doses of 1, 3, 10, and 30 mg/kg/ h, respectively. These results suggest that YM466 is a safe antithrombotic agent with low bleeding risk, and that plasma anti-FXa activity may be a suitable parameter for monitoring its antithrombotic effect. Drug Dev.

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In Vitro Characterization of a Novel Factor Xa Inhibitor, RPR 130737

Chu¹,

Brown²,

Colussi³

et al. 2000

Thrombosis Research

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RPR120844, a Novel, Specific Inhibitor of Coagulation Factor Xa Inhibits Venous Thrombosis in the Rabbit

Cited by 18 publications

References 13 publications

Role of Tissue Factor in Thrombosis. Coagulation-Inflammation-Thrombosis circuit

Role of Tissue Factor in Thrombosis. Coagulation-Inflammation-Thrombosis circuit

Antithrombotic effects of YM466, a synthesized direct inhibitor of factor Xa, in an arterio‐venous shunt thrombosis model in squirrel monkeys

In Vitro Characterization of a Novel Factor Xa Inhibitor, RPR 130737

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