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
Lewis C. Cantley sites in an arbitrary protein. In later research, the oriented peptide library approach has also been used to characterize protease cleavage specificity. Modification of the original oriented peptide approach has allowed for large scale, kinome-wide determination of protein kinase specificity. In 1997, the Cantley lab discovered that the enzymes that had been referred to as type II PIP-kinases, instead of using PtdIns(4)P as a substrate, in fact required PtdIns(5)P as a substrate to produce PtdIns(4,5)P2. Further research demonstrated that PtdIns(5)P is naturally occurring in all eukaryotes. It is remarkable that of the seven naturally occurring phosphoinositides, the existence of four