The derivatives of hirudin-like peptides from the Poecilobdella manillensis exhibit antithrombotic and anti-ischemic stroke effects
Research article published in International journal of biological macromolecules (2025)
Abstract
Almost all currently approved anticoagulants interfere with hemostasis and increase the risk of bleeding complications. Thus, there is a critical need for safer anti-thrombotic drugs without bleeding risk. Hirudin has demonstrated potent antithrombotic properties, but is clinically limited due to its high bleeding risk. Hirudin variants such as bivalirudin have been developed to address this issue, yet present a similar proportional risk of bleeding. In this study, several hirudin-like peptides were identified from the salivary gland transcriptome of Poecilobdella manillensis. Guided by the structural design principles of bivalirudin, derivatives of these hirudin-like peptides were synthesized and evaluated for their antithrombotic efficacy and safety in thrombosis and ischemic stroke. Results suggested that derived peptides PM3, PM4, PM6 and PM7 can effectively inhibited the activity of thrombin in vitro. Furthermore, PM4, PM6 and PM7 exhibited robust anticoagulant activity in vivo. Importantly, PM4 and PM7 exhibited significantly lower bleeding risk compared to bivalirudin, as well as comparable efficacy in mitigating intracerebral thrombosis in a transient middle cerebral artery occlusion mouse model, without inducing intracerebral hemorrhage. These findings highlight the therapeutic potential of hirudin-like peptide derivatives as promising candidates for the treatment of thrombosis and ischemic stroke, combining efficacy with an improved safety profile.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Almost all currently approved anticoagulants interfere with hemostasis and increase the risk of bleeding complications.
Por qué esto importa para la hirudoterapia
Este estudio identificó péptidos tipo hirudina a partir del transcriptoma de la glándula salival de Poecilobdella manillensis y sintetizó derivados guiados por principios de diseño estructural de la bivalirudina. Los derivados PM3, PM4, PM6 y PM7 inhibieron eficazmente la trombina in vitro; PM4, PM6 y PM7 exhibieron actividad anticoagulante in vivo; y PM4 y PM7 mostraron un riesgo hemorrágico significativamente menor que la bivalirudina, a la vez que demostraron una eficacia comparable en la mitigación de la trombosis intracerebral en un modelo murino de oclusión transitoria de la arteria cerebral media, sin inducir hemorragia intracerebral. Esto es directamente relevante para el dominio de la ASH, ya que explora variantes de hirudina derivadas de sanguijuelas como agentes antitrombóticos y anti-ictus potencialmente más seguros. Salvedad: Los hallazgos son preclínicos, se basan en modelos murinos de trombosis e ictus isquémico con derivados peptídicos sintéticos, no con terapia con sanguijuelas vivas; no se presentan datos de seguridad ni de eficacia en humanos.
Citación
The derivatives of hirudin-like peptides from the Poecilobdella manillensis exhibit antithrombotic and anti-ischemic stroke effects
Khalid M et al. · International journal of biological macromolecules, 2025
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026