The thrombin mutant W215A/E217A shows safe and potent anticoagulant and antithrombotic effects in vivo.

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Gruber A, Cantwell AM, Di Cera E, Hanson SR

The thrombin mutant W215A/E217A shows safe and potent anticoagulant and antithrombotic effects in vivo.

J Biol Chem. 2002 Aug 2;277(31):27581-4. Epub 2002 Jun 17.

PubMed ID
12070133 [ View in PubMed
]
Abstract

Administration of the thrombin mutant W215A/E217A (WE), rationally designed for selective activation of the anticoagulant protein C, elicits safe and potent anticoagulant and antithrombotic effects in a baboon model of platelet-dependent thrombosis. The lowest dose of WE tested (0.011 mg/kg bolus) reduced platelet thrombus accumulation by 80% and was at least as effective as the direct administration of 40-fold more (0.45 mg/kg bolus) activated protein C. WE-treated animals showed no detectable hemorrhage or organ failure. No procoagulant activity could be detected for up to 1 week in baboon plasma obtained following WE administration. These results show that engineered thrombin derivatives that selectively activate protein C may represent useful therapeutic agents for the treatment of thrombotic disorders.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Drotrecogin alfaProthrombinProteinHumans
Unknown
Not AvailableDetails