Factor IXa Inhibitors as Novel Anticoagulants R1 Howard Factor IXa Inhibitors
نویسندگان
چکیده
Currently available anticoagulants are limited by modest therapeutic benefits, narrow clinical applications, increased bleeding risk, and drug-induced thrombophilia. Because factor IX plays a pivotal role in thrombin generation, it may represent a promising target for drug development. Several methods of attenuating factor IX activity, including monoclonal antibodies, synthetic active site-blocked competitive inhibitors, oral inhibitors, and RNA aptamers, have undergone investigation. This review summarizes present knowledge of factor IX inhibitors with emphasis on biology, pharmacology, preclinical data, and early-phase clinical experience in humans. (Arterioscler Thromb Vasc Biol. 2007; 27:000-000.)
منابع مشابه
Coagulation factor IXa as a target for treatment and prophylaxis of venous thromboembolism.
Venous thromboembolism remains a frequent cause of vascular death. Despite advances in anticoagulant drug development, unmet needs remain, including limited treatment options for patients with severe renal impairment and the inability to fully reverse the effects of anticoagulants approved or in late-stage development. Because coagulation factor IXa plays a pivotal role in tissue factor-mediate...
متن کاملDVT: A New Era in Anticoagulant Therapy Coagulation Factor IXa as a Target for Treatment and Prophylaxis of Venous Thromboembolism
Venous thromboembolism remains a frequent cause of vascular death. Despite advances in anticoagulant drug development, unmet needs remain, including limited treatment options for patients with severe renal impairment and the inability to fully reverse the effects of anticoagulants approved or in late-stage development. Because coagulation factor IXa plays a pivotal role in tissue factor-mediate...
متن کاملRapid Publication Protease Nexin-2/Amyloid ft Protein Precursor A Tight-binding Inhibitor of Coagulation Factor IXa
Protease nexin-2/amyloid 6 protein precursor (PN-2/A#PP) is an abundant, secreted platelet protein which is a potent inhibitor of coagulation Factor XIa. We examined other potential anticoagulant activities of PN-2/Ai8PP. Purified Kunitz protease inhibitor domain of PN-2/A8PP and PN-2/ABPP itself were found to prolong the coagulation time of plasma and pure Factor IXa. The Kunitz protease inhib...
متن کاملDesign and prediction of new anticoagulants as a selective Factor IXa inhibitor via three-dimensional quantitative structure-property relationships of amidinobenzothiophene derivatives
Factor IXa (FIXa), a blood coagulation factor, is specifically inhibited at the initiation stage of the coagulation cascade, promising an excellent approach for developing selective and safe anticoagulants. Eighty-four amidinobenzothiophene antithrombotic derivatives targeting FIXa were selected to establish three-dimensional quantitative structure-activity relationship (3D-QSAR) and three-dime...
متن کاملExploring potential anticoagulant drug formulations using thrombin generation test
Many anticoagulant drugs inhibiting proteins of the coagulation cascade have been developed. The main targets of anticoagulant drugs are thrombin and factor Xa; inhibiting these factors delays thrombus growth, thus preventing thrombosis while increasing bleeding risk. A balance between thrombosis and bleeding is ensured in the 'therapeutic window' of the anticoagulant drug concentration range. ...
متن کامل