Direct thrombin inhibitors.
Thrombin not only plays an important role in thrombosis and haemostasis but may also be involved in other pathological situations such as the progression of atherosclerotic plaque formation, inflammatory response and neurodegenerescence. It is therefore important to be able to control the action and/or the generation of this enzyme. With this aim in view, a great number of synthetic or recombinant direct thrombin inhibitors have recently been made. They block either the thrombin catalytic site or an anion-binding exosite which is a recognition site for some of its substrates (fibrinogen, thrombin receptor, thrombomodulin, heparin cofactor II) or act on both sites. Some of these inhibitors have revealed a number of advantages over heparin in experimental animal models of thrombosis and haemorrhagic risk. On-going clinical studies with some candidates will establish their real interest for patients.
Maffrand
J P
JP
Sanofi Recherche, Toulouse, France.
D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006487:Hemostasis; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry
D000925:Anticoagulants; D000991:Antithrombins; D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D013917:Thrombin