Enhancement of recombinant tissue-type plasminogen activator thrombolysis with a selective factor Xa inhibitor derived from the leech Hirudo medicinalis

Kornowski, Ran; Eldor, A; Mm, Werber; Ezov, Nathan; Zwang, E; Nimrod, A.; Chernine, A; Finkelstein, Ariel; Panet, Amos; Laniado, Shlomo; Keren, G

doi:10.1097/00019501-199612000-00005

Cited by 7 publications

(3 citation statements)

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“…Additional antistasin-type proteins known to inhibit factor Xa include ghilanten [93] and yagin [82]. In contrast, guamerin I [97] and guamerin II [88] are specific inhibitors of neutrophil and pancreas elastases, whereas hirustasin is a potent inhibitor of trypsin, chymotrypsin, cathepsin G and tissue kallikrein [55].…”

Section: Antistasins As a Representative Leech Salivary Protein Familymentioning

confidence: 99%

European Medicinal Leeches—New Roles in Modern Medicine

Lemke

Vilcinskas

2020

Biomedicines

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Before the advent of modern medicine, natural resources were widely used by indigenous populations for the prevention and treatment of diseases. The associated knowledge, collectively described as folk medicine or traditional medicine, was largely based on trial-and-error testing of plant extracts (herbal remedies) and the use of invertebrates, particularly medicinal maggots of the blowfly Lucilia sericata and blood-sucking leeches. The widespread use of traditional medicine in the West declined as scientific advances allowed reproducible testing under controlled conditions and gave rise to the modern fields of biomedical research and pharmacology. However, many drugs are still derived from natural resources, and interest in traditional medicine has been renewed by the ability of researchers to investigate the medical potential of diverse species by high-throughput screening. Likewise, researchers are starting to look again at the benefits of maggot and leech therapy, based on the hypothesis that the use of such animals in traditional medicine is likely to reflect the presence of specific bioactive molecules that can be developed as drug leads. In this review, we consider the modern medical benefits of European medicinal leeches based on the systematic screening of their salivary proteins.

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Section: Antistasins As a Representative Leech Salivary Protein Familymentioning

confidence: 99%

European Medicinal Leeches—New Roles in Modern Medicine

Lemke

Vilcinskas

2020

Biomedicines

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“…An FXa inhibitor was also identified in the saliva of H. medicinalis. This novel FXa inhibitor was shown to be more effective antithrombotic agent compared to hirudin or heparin, as it significantly shortened the time to thrombolysis induced by tissue plasminogen activator, based on studies carried out on rabbits [38].…”

Section: Bioactive Compounds In Leech Salivamentioning

confidence: 99%

An overview of leech and its therapeutic applications

2015

J Coast Life Med

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“…Besides other proteins extracted from various leeches such as yagin derived from Hirudo medicinalis [188], or another one from the giant Amazonian leech, Haementeria ghilianii [189], selective FXa inhibitors were isolated and characterized from e.g. the salivary gland of the black fly, Simulium vittatum [190], or Ancylostoma sp.…”

Section: Natural Fxa Inhibitorsmentioning

confidence: 99%

Pharmacological Strategies for Inhibition of Thrombin Activity

Alban

2008

CPD

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For decades, the options for therapeutic anticoagulation were limited to unfractionated heparin (UFH) and vitamin K antagonists (VKA), and their well-known limitations had to be accepted. With the introduction of the various LMWHs, the short-term anticoagulation could be much improved. The heparins delivered the proof of concept that FXa and thrombin represent suitable targets for therapeutic anticoagulation. Consequently, the search for new anticoagulants focus on inhibitors of thrombin or FXa. Apart from the VKA, the anticoagulants presently available or in an advanced stage of development can thus be divided in two classes: One are the glyco-anticoagulants with the natural sulfated glycosaminoglycans (GAGs) (UFH, LMWHs, and danaparoid) and the synthetic oligosaccharides (OS) (fondaparinux, idraparinux, and SR123781A). The other class are the xenobiotic anticoagulants, i.e. proteins and synthetic chemical entities. Die glyco-anticoagulants act partially (GAGs) or exclusively (oligosaccharides) by catalysing antithrombin, whereas the xenobiotic anticoagulants are direct inhibitors of either thrombin or FXa. At present, three direct thrombin inhibitors (DTI) (lepirudin, argatroban, and bivalirudin) are clinically used for limited indications, whereas there is still no direct FXa inhibitor available. The DTI ximelagatran represented the first oral anticoagulant since the introduction of VKA, but was withdrawn due to safety concerns. Among numerous drug candidates in the clinical development, two orally active anticoagulants dabigatran etexilate, a DTI, and rivaroxaban, the direct FXa inhibitor, are in the most advanced stage of development and may allow a paradigm change in anticoagulation in the foreseeable future. This review describes the pharmacological profile of all these anticoagulants.

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Enhancement of recombinant tissue-type plasminogen activator thrombolysis with a selective factor Xa inhibitor derived from the leech Hirudo medicinalis

Cited by 7 publications

References 0 publications

European Medicinal Leeches—New Roles in Modern Medicine

European Medicinal Leeches—New Roles in Modern Medicine

An overview of leech and its therapeutic applications

Pharmacological Strategies for Inhibition of Thrombin Activity

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