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Inhibitors of Thrombin and Factor Xa

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Book cover Proteases as Targets for Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 140))

Abstract

In medicine today, much effort is being made to develop new protease inhibitors for use as anticoagulants in multiple disease states. Deep venous thrombosis and pulmonary embolism, in particular, are major medical problems in the developed world. Similarly, myocardial infarction, stroke, and peripheral vascular disease are arterial thromboses for which the addition of anticoagulant/antiplatelet agents have resulted in reduction of adverse events upon presentation and improved treatment outcomes. Therapies for both venous and arterial thrombosis represent major growth areas in the pharmaceutical industry. The basis for many of these anticoagulant agents has arisen from naturally occurring protease inhibitors in man and in other creatures. This interest arises from a need in clinical medicine to improve anticoagulant therapeutics for both naturally occurring disease processes and new medical therapeutic interventions. Characterization of nature’s inhibitors can provide for the development of important therapeutics. Development of novel anticoagulants needs to consider the major clot-forming enzymes in the hemostatic system, thrombin and factor Xa. Thus, protease inhibitors to these two enzymes have the potential to serve as anticoagulants, i.e., to inhibit hemostatic clot formation. In this manuscript, the term “anticoagulants” will be used to describe agents that interfere with proteins that participate in the plasma coagulation system which has been traditionally termed the coagulation cascade. The term “antiplatelet agents” will be used to describe entities that specifically interfere with platelet activation only. Both anticoagulants and antiplatelet agents prevent thrombosis in blood vessels. The term “antithrombotics” will be used in this manuscript to indicate combined anticoagulant and antiplatelet activity of agents.

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Authors and Affiliations

  1. Department of Internal Medicine and Pathology, University of Michigan, 5301 MSRB III, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109-0640, USA

    A. H. Schmaier

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  1. A. H. Schmaier
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  1. Max-von-Pettenkofer Institut für medizinische Mikrobiologie, LM Universität, LS Virologie Pettenkoferstr. 9a, D-80336, München, Germany

    Klaus von der Helm Ph.D., M.D.

  2. DuPont Pharmaceutical Co Research and Development, Edperimental Station, E336/31B, Wilmington, DE, 19880-0336, USA

    Bruce D. Korant Ph.D.

  3. Drug Discovery and Development, Source Precision Medicine, 2425 N. 55th Street, Suite 111, Boulder, CO, 80301, USA

    John C. Cheronis M.D., Ph.D. (Vice President) (Vice President)

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© 2000 Springer-Verlag Berlin Heidelberg

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Schmaier, A.H. (2000). Inhibitors of Thrombin and Factor Xa. In: von der Helm, K., Korant, B.D., Cheronis, J.C. (eds) Proteases as Targets for Therapy. Handbook of Experimental Pharmacology, vol 140. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57092-6_15

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  • DOI: https://doi.org/10.1007/978-3-642-57092-6_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63023-1

  • Online ISBN: 978-3-642-57092-6

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