Factor VIIa and Factor IXa Inhibitors as Anticoagulants: A Review

Abstract:

Introduction: Anticoagulants are used as preventive agents in deep vein thrombosis to prevent blood clots, venous and arterial thromboembolism, but the current therapy of anticoagulants have several limitations like patient variable response, enhanced chances of bleeding and heparin-induced thrombocytopenia (HIT). Factor VIIa and factor IXa play an important role in coagulation cascade and hence are promising targets for drug development. FIXa has been targeted by various means including oral inhibitors (TTP889), monoclonal antibodies (SB249417) and RNA aptamers which have passed various phases of clinical trials. Objectives: Though advances in development of inhibitors of FVIIa/TF and FIXa have reached various phases of clinical trials none of the clinical trial candidates have reached the market. Methodology: This review summarizes available information on FVIIa/TF and FIXa, their active site, crystallographic structure, available inhibitors, earlyphase clinical trial study and also the recent efforts in the discovery of FVIIa/TF and FIXa inhibitors. Summary: Despite the fact that more complexity is observed in designing of anticoagulant as FVIIa/TF complex and FIXa inhibitors, these will remain an important and validated target for the design and development of anticoagulants.

Key words: Anticoagulants, FVIIa/TF, FIXa, Inhibitors, Serine protease.