title: Dose-dependent antithrombotic activity of an orally active tissue factor/factor VIIa inhibitor without concomitant enhancement of bleeding propensity.
abstract: The discovery of a highly potent and selective tissue factor/factor VIIa inhibitor is described. Upon oral administration of its double prodrug in the guinea pig, a dose-dependent antithrombotic effect is observed in an established model of arterial thrombosis without prolonging bleeding time. The pharmacodynamic properties of this selective inhibitor are compared to the behaviour of a mixed factor VIIa/factor Xa inhibitor.
authors.affiliation: F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. katrin.groebke_zbinden@roche.com
authors.forename: Katrin
authors.initials: K
authors.lastname: Groebke Zbinden
authors.forename: David W
authors.initials: DW
authors.lastname: Banner
authors.forename: Kurt
authors.initials: K
authors.lastname: Hilpert
authors.forename: Jacques
authors.initials: J
authors.lastname: Himber
authors.forename: Thierry
authors.initials: T
authors.lastname: Lavé
authors.forename: Markus A
authors.initials: MA
authors.lastname: Riederer
authors.forename: Martin
authors.initials: M
authors.lastname: Stahl
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Tschopp
authors.forename: Ulrike
authors.initials: U
authors.lastname: Obst-Sander
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001760:Bleeding Time; D019774:Blood Coagulation Factor Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013925:Thromboplastin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D019774:Blood Coagulation Factor Inhibitors; D011355:Prodrugs; D013925:Thromboplastin; D015942:Factor VIIa