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 nor its structure fully determined until 1976. Full length hirudin is made up of 65 amino acids. These amino acids are organized into a compact N-terminal domain containing three disulfide bonds and a C-terminal domain that is completely disordered when the protein is un-complexed in solution. Amino acid residues 1-3 form a parallel beta- strand with residues 214-217 of thrombin, the nitrogen atom of residue 1 making a hydrogen bond with the Ser-195 O gamma atom of the catalytic site. The C-terminal domain makes numerous electrostatic interactions with an anion-binding exosite of thrombin, while the last five residues are in