This Article Full Text Full Text (PDF) All Versions of this Article: 27/9/1895    most recent ATVBAHA.107.148304v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shirk, R. A. Articles by Vlasuk, G. P. Search for Related Content PubMed PubMed Citation Articles by Shirk, R. A. Articles by Vlasuk, G. P.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1895.)
© 2007 American Heart Association, Inc.

Brief Reviews

Inhibitors of Factor VIIa/Tissue Factor

Rebecca A. Shirk; George P. Vlasuk

From the Department of Cardiovascular and Metabolic Diseases Research, Wyeth Research, Collegeville, Pa.

Correspondence to Rebecca A. Shirk, PhD, Wyeth Research, P.O. Box 42528, Philadelphia, PA 19101-2528. E-mail shirkr{at}wyeth.com

Series Editor: Jeffrey I. Weitz
Emerging Anticoagulant Drugs
ATVB In Focus

Previous Brief Reviews in this Series:

•Turpie AGG. Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol. 2007;27:1238–1247.
•Howard EL, Becker KCD, Rusconi CP, Becker RC. Factor IXa inhibitors as novel anticoagulants. Arterioscler Thromb Vasc Biol. 2007;27:722–727.
•Weitz J. Emerging anticoagulant drugs. Arterioscler Thromb Vasc Biol. 2007;27:721.

The formation of the proteolytic complex composed of the serine protease Factor VIIa and the cell-associated glycoprotein tissue factor (FVIIa/TF) initiates a cascade of amplified zymogen activation reactions leading to thrombus formation. The critical role of the coagulation cascade in pathological thrombosis has been the basis for significant efforts to design selective inhibitors of the protease components as new anticoagulant alternatives for the treatment of thrombotic diseases. However, for the new generation of anticoagulant drugs in development that primarily target protease complexes distal from FVIIa/TF, the differential between efficacy and safety as defined by bleeding is unresolved. Targeting the FVIIa/TF complex has several theoretical advantages that exploit the amplified nature of the coagulation cascade. However, progress on the development of clinical-stage FVIIa/TF-based anticoagulants has not been as successful to date. This review summarizes recent efforts in the discovery of synthetic inhibitors of FVIIa/TF.

The factor VIIa/tissue factor complex is an attractive target for novel anticoagulants. This review summarizes recent efforts to discover synthetic inhibitors of factor VIIa/tissue factor and the remaining challenges to developing a novel drug.

Key Words: anticoagulants • factor VIIa (FVIIa) • tissue factor • serine protease inhibitors • coagulation