Human in vitro pharmacodynamic profile of the selective Factor Xa inhibitor ZK-807834 (CI-1031)

Joseph M. Post; Mark E. Sullivan; Dana Abendschein; Janice Ewing; Josephine W. Hinchman; David R. Light

doi:10.1016/S0049-3848(02)00024-5

Human in vitro pharmacodynamic profile of the selective Factor Xa inhibitor ZK-807834 (CI-1031)

Joseph M. Post
, Mark E. Sullivan
, Dana Abendschein
, Janice Ewing
, Josephine W. Hinchman
, David R. Light

Division of Cardiology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

ZK-807834 (also known as CI-1031) is a small molecule that potently and selectively inhibits Factor Xa. Studies in animals have shown that ZK-807834 attenuates thrombosis and thrombus progression after fibrinolysis and exhibits an increased antithrombotic-to-bleeding risk ratio compared with conventional agents. The present study describes the human in vitro anticoagulant and pharmacodynamic profile ZK-807834. Consistent with its selective inhibition of Factor Xa, ZK-807834 in the range of 0.3-0.5 μM prolonged prothrombin time (PT) and activated partial thromboplastin time (aPPT) twofold without affecting thrombin time (TT). Intersubject variability of in vitro anticoagulant activity was nominal and gender-independent. ZK-807834 inhibited Factor Xa in clot-bound prothrombinase with an average IC₅₀ of 10±7 (S.D.) nM. ZK-807834 exhibited no direct effect on ADP- or collagen-induced platelet aggregation. Based on the potency and specificity, ZK-807834 may represent an important advance in the development of selective and safe antithrombotics.

Original language	English
Pages (from-to)	347-352
Number of pages	6
Journal	Thrombosis Research
Volume	105
Issue number	4
DOIs	https://doi.org/10.1016/S0049-3848(02)00024-5
State	Published - Feb 15 2002

Keywords

Anticoagulant
Factor Xa inhibitor
ZK-807834

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10.1016/S0049-3848(02)00024-5

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title = "Human in vitro pharmacodynamic profile of the selective Factor Xa inhibitor ZK-807834 (CI-1031)",

abstract = "ZK-807834 (also known as CI-1031) is a small molecule that potently and selectively inhibits Factor Xa. Studies in animals have shown that ZK-807834 attenuates thrombosis and thrombus progression after fibrinolysis and exhibits an increased antithrombotic-to-bleeding risk ratio compared with conventional agents. The present study describes the human in vitro anticoagulant and pharmacodynamic profile ZK-807834. Consistent with its selective inhibition of Factor Xa, ZK-807834 in the range of 0.3-0.5 μM prolonged prothrombin time (PT) and activated partial thromboplastin time (aPPT) twofold without affecting thrombin time (TT). Intersubject variability of in vitro anticoagulant activity was nominal and gender-independent. ZK-807834 inhibited Factor Xa in clot-bound prothrombinase with an average IC50 of 10±7 (S.D.) nM. ZK-807834 exhibited no direct effect on ADP- or collagen-induced platelet aggregation. Based on the potency and specificity, ZK-807834 may represent an important advance in the development of selective and safe antithrombotics.",

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AU - Post, Joseph M.

AU - Sullivan, Mark E.

AU - Abendschein, Dana

AU - Ewing, Janice

AU - Hinchman, Josephine W.

AU - Light, David R.

PY - 2002/2/15

Y1 - 2002/2/15

N2 - ZK-807834 (also known as CI-1031) is a small molecule that potently and selectively inhibits Factor Xa. Studies in animals have shown that ZK-807834 attenuates thrombosis and thrombus progression after fibrinolysis and exhibits an increased antithrombotic-to-bleeding risk ratio compared with conventional agents. The present study describes the human in vitro anticoagulant and pharmacodynamic profile ZK-807834. Consistent with its selective inhibition of Factor Xa, ZK-807834 in the range of 0.3-0.5 μM prolonged prothrombin time (PT) and activated partial thromboplastin time (aPPT) twofold without affecting thrombin time (TT). Intersubject variability of in vitro anticoagulant activity was nominal and gender-independent. ZK-807834 inhibited Factor Xa in clot-bound prothrombinase with an average IC50 of 10±7 (S.D.) nM. ZK-807834 exhibited no direct effect on ADP- or collagen-induced platelet aggregation. Based on the potency and specificity, ZK-807834 may represent an important advance in the development of selective and safe antithrombotics.

AB - ZK-807834 (also known as CI-1031) is a small molecule that potently and selectively inhibits Factor Xa. Studies in animals have shown that ZK-807834 attenuates thrombosis and thrombus progression after fibrinolysis and exhibits an increased antithrombotic-to-bleeding risk ratio compared with conventional agents. The present study describes the human in vitro anticoagulant and pharmacodynamic profile ZK-807834. Consistent with its selective inhibition of Factor Xa, ZK-807834 in the range of 0.3-0.5 μM prolonged prothrombin time (PT) and activated partial thromboplastin time (aPPT) twofold without affecting thrombin time (TT). Intersubject variability of in vitro anticoagulant activity was nominal and gender-independent. ZK-807834 inhibited Factor Xa in clot-bound prothrombinase with an average IC50 of 10±7 (S.D.) nM. ZK-807834 exhibited no direct effect on ADP- or collagen-induced platelet aggregation. Based on the potency and specificity, ZK-807834 may represent an important advance in the development of selective and safe antithrombotics.

KW - Anticoagulant

KW - Factor Xa inhibitor

KW - ZK-807834

UR - https://www.scopus.com/pages/publications/0037082373

U2 - 10.1016/S0049-3848(02)00024-5

DO - 10.1016/S0049-3848(02)00024-5

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AN - SCOPUS:0037082373

SN - 0049-3848

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SP - 347

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JO - Thrombosis Research

JF - Thrombosis Research

IS - 4

ER -

Human in vitro pharmacodynamic profile of the selective Factor Xa inhibitor ZK-807834 (CI-1031)

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Keywords

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