Alfimeprase: pharmacology of a novel fibrinolytic metalloproteinase for thrombolysis.
Alfimeprase is a recombinantly produced, truncated form of fibrolase, a known directly fibrinolytic zinc metalloproteinase that was first isolated from the venom of the southern copperhead snake (Agkistrodon contortrix contortrix). Both fibrolase and alfimeprase have been shown to have direct proteolytic activity against the fibrinogen Aalpha chain. In vivo pharmacology studies have shown that thrombolysis with alfimeprase is up to 6 times more rapid than with plasminogen activators. Alfimeprase can be bound and neutralized by serum alpha(2)-macroglobulin, a prevalent mammalian protease inhibitor which is capable of forming a macromolecular complex with alfimeprase. As a result, systemic bleeding complications have been greatly reduced due to the inhibitory effects of alpha(2)-macroglobulin. This article reviews the biochemical in vitro and in vivo characteristics of this novel acting thrombolytic.
Toombs
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Product Development/Mailstop 27-5-A, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA 91320, USA. ctoombs@amgen.com
D000818:Animals; D005343:Fibrinolytic Agents / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015912:Thrombolytic Therapy / Q000379:methods; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000494:pharmacology
D005343:Fibrinolytic Agents; D000511:alpha-Macroglobulins; D008666:Metalloendopeptidases; C436755:alfimeprase; C058789:fibrolase