Factor IXa Inhibitors as Novel Anticoagulants

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 27; no. 4; pp. 722 - 727
• Main Authors: Howard, Emily L, Becker, Kristian C.D, Rusconi, Christopher P, Becker, Richard C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.04.2007; Hagerstown, MD Lippincott
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Anticoagulants - pharmacology; Aptamers, Nucleotide - pharmacology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Coagulation - physiology; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Factor IX - chemistry; Factor IX - physiology; Factor IXa - antagonists & inhibitors; Factor IXa - immunology; Heart; Humans; Medical sciences; Pharmacology. Drug treatments; Structure-Activity Relationship; Vascular disease; RNA aptamers; Factor IX; Atherosclerosis; Cardiovascular disease; Anticoagulant; Monoclonal antibody; anticoagulants■ coagulation■ factor IX (fIX); monoclonal antibodies (mAb); Coagulation factor
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000259363.91070.f1

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 tissue factor (TF)–mediated 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.