Bivalirudin Bivalirudin Bivalirudin (Angiomax or Angiox, manufactured by The Medicines Company) is a direct thrombin inhibitor (DTI). Chemically, it is a synthetic congener of the naturally occurring drug hirudin (found in the saliva of the medicinal leech "Hirudo medicinalis"). Bivalirudin is a DTI that overcomes many limitations seen with indirect thrombin inhibitors, such as heparin. Bivalirudin is a short, synthetic peptide. It is a potent and highly specific inhibitor of thrombin. It inhibits both circulating and clot-bound thrombin, while also inhibiting thrombin-mediated platelet activation and aggregation. Bivalirudin has a quick onset of action and a short half-life. It does not bind
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