New derivative of staphylokinase SAK-RGD-K2-Hirul exerts thrombolytic effects in the arterial thrombosis model in rats
Comparative study published in Pharmacological reports : PR (2011)
Abstract
SAK-RGD-K2-Hir and SAK-RGD-K2-Hirul are recombinant proteins that are derivatives of r-SAK (recombinant staphylokinase). They are characterized by their fibrin-specific plasminogen activation properties and their antithrombin and antiplatelet activities. The difference between these proteins is the presence of the antithrombotic fragment (hirudin or hirulog) in the C-terminal portion of the r-SAK. The aim of the present study was to examine the thrombolytic potentials of SAK-RGD-K2-Hir and SAK-RGD-K2-Hirul in an electrically induced carotid artery thrombosis model in rats and to compare the potentials to that of r-SAK. We determined that a bolus injection of SAK-RGD-K2-Hirul was more effective than one of r-SAK in the improvement and maintenance of carotid patency and in arterial thrombus weight reduction; however, it had the same potency as SAK-RGD-K2-Hir. The bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in the animals that were treated with either dose (1.5 or 3.0 mg/kg) of SAK-RGD-K2-Hir or SAK-RGD-K2-Hirul, whereas no changes were observed in the plasma fibrinogen concentration or the α2 plasmin inhibitor level. r-SAK alone did not change the bleeding time or coagulation parameters. In conclusion, our findings demonstrate the thrombolytic activity of intravenous bolus injection of the novel thrombolytic agent SAK-RGD-K2-Hirul in rats. Although this protein compares favorably with r-SAK, we were unable to show the presence of any beneficial effects of SAK-RGD-K2-Hirul over those of SAK-RGD-K2-Hir. Furthermore, our results suggest that high doses of SAK-RGD-K2-Hirul bear the risk of bleeding.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
SAK-RGD-K2-Hir and SAK-RGD-K2-Hirul are recombinant proteins that are derivatives of r-SAK (recombinant staphylokinase).
Por qué esto importa para la hirudoterapia
Este estudio examinó el potencial trombolítico de un derivado recombinante de estafilocinasa, SAK-RGD-K2-Hirul, que incorpora un fragmento antitrombótico de tipo hirulog (derivado de hirudina), en un modelo de trombosis de la arteria carótida inducida eléctricamente en ratas. Una inyección en bolo de SAK-RGD-K2-Hirul fue más eficaz que la r-SAK sola para mejorar la permeabilidad carotídea y reducir el peso del trombo, comparable a la variante SAK-RGD-K2-Hir que contiene el fragmento de hirudina, pero las dosis elevadas conllevaron riesgo hemorrágico. Esto demuestra la contribución funcional de un péptido derivado de hirudina dentro de una proteína de fusión trombolítica multimodal, relevante para el diseño de fármacos antitrombóticos basados en hirudina. Advertencia: se trata de un estudio en animales (ratas) sobre una proteína de fusión recombinante, no sobre hirudina natural ni sobre hirudoterapia con sanguijuelas vivas, y no se demostró ninguna ventaja sobre la variante con el fragmento de hirudina.
Citación
New derivative of staphylokinase SAK-RGD-K2-Hirul exerts thrombolytic effects in the arterial thrombosis model in rats
Szemraj J et al. · Pharmacological reports : PR, 2011
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026