Factor Xa inhibitors

Abstract

Factor Xa is the serine protease that activates prothrombin to yield thrombin. Inhibitors of factor Xa play a crucial role in curtailing thrombin generation. Major factor Xa inhibitors present in blood are antithrombin III (ATIII) and tissue factor pathway inhibitor (TFPI). Substances inhibiting factor Xa are also found in certain hematophagous animals to facilitate feeding. Evaluation of tick anticoagulant peptide (TAP), leech-derived antistatin (ATS), and ecotin using animal thrombic models has confirmed that specific blockage of factor Xa activity is an effective antithrombotic strategy. Recombinant compounds of TAP and ATS have also been evaluated on thrombotic models. In recent years, several laboratories have been engaged in the design of low molecular weight synthetic factor Xa inhibitors for use as anticoagulants in the treatment and/or prevention of thrombosis.