title: Alfimeprase: a novel recombinant direct-acting fibrinolytic.
abstract: Alfimeprase is a recombinant, direct-acting fibrinolytic zinc metalloprotease. Alfimeprase has direct proteolytic activity primarily against the fibrin(ogen) Aalpha chain. Alfimeprase is covalently bound and neutralised by serum alpha(2)-macroglobulin, a prevalent mammalian protease inhibitor. Preclinical pharmacology studies have shown that fibrinolysis with alfimeprase is up to sixfold more rapid than with select plasminogen activators, such as tissue-type plasminogen activator and urokinase. Alfimeprase directly delivered to a site of thrombosis has the potential to be a fast and effective fibrinolytic, which does not generate the systemic lytic state seen with plasminogen activators that is associated with major bleeding, including intracerebral haemorrhage. Phase I and II studies in individuals with arterial or venous thrombotic events indicate that alfimeprase is active and generally well tolerated.
authors.affiliation: Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070, USA. sdeitcher@nuvelo.com
authors.forename: Steven R
authors.initials: SR
authors.lastname: Deitcher
authors.forename: Walter D
authors.initials: WD
authors.lastname: Funk
authors.forename: James
authors.initials: J
authors.lastname: Buchanan
authors.forename: Shouchun
authors.initials: S
authors.lastname: Liu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Levy
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Toombs
mesh_terms: D000818:Animals; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008666:Metalloendopeptidases / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015507:Drugs, Investigational; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C436755:alfimeprase