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Progress Article : Allosteric inhibitors of thrombin
Preetpal S Sidhu
University of Wisconsin
Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, WI, 53211, USA.
Thrombotic disorders such as deep vein thrombosis and venous thrombosis are one of the leading causes of death in the modern society. It is estimated that the mortality may reach 23.6 million by the end of 2030. 1 in 1000 people suffers from thrombotic disorder. Treatment of thrombotic diseases heavily relied on heparin and coumarin from the last five decades. Recently, hirudin, argatroban and dabigatran were approved for few thrombotic conditions. However, all of these drugs are associated with serious life-threatening side effects and need medical supervision for patients on therapy. Despite enormous effort and advancement in understanding the coagulation cascade, no significant progress has been made. Thrombin is the most important and highly targeted protease in the coagulation cascade. Structurally, thrombin displays multiple distinct ligand-binding sites that can modulate its activity and interactions with other molecules in the blood.

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