Description
Reteplase was launched in Germany and the US for acute myocardial
infarction. Retevase is a single chain recombinant form of tissue plasminogen
activator (t-PA) with all except the kringle-2 and protease domains deleted. When
expressed in E. coli the inactive form is produced and stored in inclusion bodies.
After purification and an in vitro refolding process the active form is obtained. The
expression in E. coli gives rise to a non-glycosylated protein. This and the deletion of
several domains allows reteplase to have a longer half-life and a slower clearance.
Despite the deletions and refolding the catalytic center remains intact. The kringle-2
domain allows binding to lysine in fibrin which makes it effective for the rapid and
complete lysis of coronary thrombi. While it does not have a high affinity for binding
to fibrin, its activity is stimulated by it and has the same level of in vivo fibrin
selectivity as human t-PA. It has a low affinity for endothelial cells and can be
administered as a double bolus injection. Netaplase, a similar recombinant form of t-
PA, was launched by MitsuiIMochida in Japan.
Originator
Boehringer Mannheim (Germany)
Uses
Myocardial infarction therapy; plasminogen activator.
General Description
Reteplase (Retavase) is a deletion mutant variant of tPAthat is produced in recombinant E. coli. The deletions arein domains responsible for half-life, fibrin affinity, andthrombolytic potency. It consists of the kringle-2 domain and protease domain of tPA but lacks the kringle-1 domainand the growth factor domain. It is considered a thirdgenerationthrombolytic agent and has a mechanism of actionsimilar to that of alteplase. Reteplase acts directly bycatalyzing the cleavage of plasminogen and initiatingthrombolysis. It has high thrombolytic potency.
