Ecotin: Exploring a feasible antithrombotic profile

Luciana Serrão Wermelinger, Flávia Serra Frattani, Tatiana Lobo, Charles S. Craik, Helena Carla Castro, Russolina Benedeta Zingali

Research output: Contribution to journalArticle


Ecotin is an Escherichia coli-derived protein that can inhibit serine proteases. It has been suggested that this protein (ecotin-WT) and some of its variants could be used to develop a prototype to treat thrombosis. In this work, the effect of ecotin-WT and a variant of this protein harboring two mutations (Met84Arg and Met85Arg, ecotin-RR) were analyzed to determine their ability to prevent thrombus formation using in vivo models. Ecotins were analyzed in vitro using the coagulation tests. An in vivo venous thrombosis rat model and a pulmonary thromboembolism mouse model were used to investigate the antithrombotic activity. The bleeding time in rats using a tail-transection model was evaluated as a possible side effect caused by the administration of these proteins. Ecotin-RR was more effective in inhibiting thrombin than ecotin-WT. Both ecotins presented similar mechanisms of anticoagulation activity and were able to decrease thrombus formation. In contrast, only ecotin-RR increased survival rates in the in vivo pulmonary thromboembolism model, reinforcing the antithrombotic activity of ecotin-RR. Ecotin-WT and more so ecotin-RR showed potent antithrombotic effects, not associated with bleeding. The presented results indicate that ecotin-WT and ecotin-RR may be new scaffolds that could be used to develop anticoagulation molecules.

Original languageEnglish
Pages (from-to)296-303
Number of pages8
JournalInternational Journal of Biological Macromolecules
Publication statusPublished - 1 Jul 2015
Externally publishedYes



  • Ecotin
  • Factor xa inhibitor
  • Thrombin inhibitor

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Wermelinger, L. S., Frattani, F. S., Lobo, T., Craik, C. S., Castro, H. C., & Zingali, R. B. (2015). Ecotin: Exploring a feasible antithrombotic profile. International Journal of Biological Macromolecules, 78, 296-303.