Factor IXa inhibitors as novel anticoagulants.
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.
Howard
Emily L
EL
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Becker
Kristian C D
KC
Rusconi
Christopher P
CP
Becker
Richard C
RC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000494:pharmacology; D001777:Blood Coagulation / Q000502:physiology; D005164:Factor IX / Q000737:chemistry / Q000502:physiology; D015949:Factor IXa / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D052157:Aptamers, Nucleotide; D005164:Factor IX; D015949:Factor IXa