Discovery and development of direct Xa inhibitors Xa was identified as a promising target for the development of new anticoagulants in the early 1980s. In 1987 the first factor Xa inhibitor, the naturally occurring compound antistasin, was isolated from the salivary glands of the Mexican leech "Haementeria officinalis". Antistasin is a polypeptide and a potent Xa inhibitor. In 1990 another naturally occurring Xa inhibitor was isolated, tick anticoagulant peptide (TAP) from extracts of the tick "Ornithodoros moubata". TAP and antistasin were used to estimate factor Xa as a drug target. Blood coagulation is a complex process by which the blood forms clots. It is an essential part
Hirudin a helical loop that forms many hydrophobic contacts. Natural rudin contains a mixture of various isoforms of the protein. However, recombinant techniques can be used to produce homogeneous preparations of hirudin. A key event in the final stages of blood coagulation is the conversion of fibrinogen into fibrin by the serine protease enzyme thrombin. Thrombin is produced from prothrombin, by the action of an enzyme, prothrombinase (Factor Xa along with Factor Va as a cofactor), in the final states of coagulation. Fibrin is then cross linked by factor XIII (Fibrin Stabilizing Factor) to form a blood clot. The principal inhibitor