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Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

PAI-1 Antagonists: Predictable Indications and Unconventional Applications

Author(s): Douglas E. Vaughan, Bart M. De Taeye and Mesut Eren

Volume 8 , Issue 9 , 2007

Page: [962 - 970] Pages: 9

DOI: 10.2174/138945007781662364

Price: $65

Abstract

At present, thrombolytic agents represent the only direct way of augmenting fibrinolytic activity in humans. While these agents are proven to be efficacious in the treatment of acute thrombotic events, they are not a viable option for long-term administration. There are numerous drugs available that indirectly to increase fibrinolytic activity by reducing plasma levels of plasminogen activator inhibitor-1 (PAI-1), including ACE inhibitors, insulin-sensitizing agents, and hormone replacement therapy in women. At present, efforts are underway to develop and test synthetic, selective PAI-1 antagonists. The potential applications of PAI-1 antagonists include thrombotic disorders (arterial and venous), amyloidosis, obesity, polycystic ovarian syndrome, and perhaps even type 2 diabetes mellitus. The availability of specific PAI-1 antagonists promises to expand the limits of understanding the role the fibrinolytic system plays in human disease and break through the current confines of therapeutic options that can effectively restore and augment the activity of the fibrinolytic system.

Keywords: Plasminogen activator inhibitor-1 (PAI-1), fibrinolysis, thrombosis, arteriosclerosis


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