Alfimeprase: a novel recombinant direct-acting fibrinolytic.
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.
Deitcher
Steven R
SR
Nuvelo, Inc., 201 Industrial Road, Suite 310, San Carlos, CA 94070, USA. sdeitcher@nuvelo.com
Funk
Walter D
WD
Buchanan
James
J
Liu
Shouchun
S
Levy
Michael D
MD
Toombs
Christopher F
CF
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*
D015507:Drugs, Investigational; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C436755:alfimeprase