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 some aspects, hirudin has advantages over more commonly used anticoagulants and thrombolytics, such as heparin, as it does not interfere with the biological activity of other serum proteins, and can also act on complexed thrombin. It is difficult to extract large amounts of hirudin from natural sources, so a method for producing and purifying this protein using recombinant biotechnology has been developed. This has led to the development and marketing of a number of hirudin-based anticoagulant pharmaceutical products, such as lepirudin (Refludan), hirudin derived from "Hansenula" (Thrombexx, Extrauma) and desirudin (Revasc/Iprivask). Several other direct thrombin inhibitors are derived chemically from