Ueber den die Blutgerinnung auf hebenden Bestandtheil des medicinischen Blutegels

Franz, F.

doi:10.1007/bf01825055

Cited by 44 publications

(4 citation statements)

References 3 publications

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“…The question arises: What makes a hirudin a hirudin? Historically, the term ‘hirudin’ was introduced by Franz and Jacoby and simply refers to the genus of the respective source, the European medicinal leech, H. medicinalis . A more advanced definition of hirudin may be based on a combination of biological, functional, structural, and evolutionary properties.…”

Section: Discussionmentioning

confidence: 99%

Hirudin or hirudin‐like factor ‐ that is the question: insights from the analyses of natural and synthetic HLF variants

et al. 2019

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The hirudin‐like factor 1 (HLF1) of Hirudo medicinalis belongs to a new class of leech‐derived factors. In previous investigations, HLF1 did not exhibit anticoagulatory activities. Here, we describe the analysis of natural and synthetic variants of HLF1 and HLF‐Hyb, a yet uncharacterized member of the HLF family. Modifications within the N terminus of HLF1 have a strong impact on its activity. Some variants of HLF1 exhibit thrombin‐inhibiting activity comparable to hirudins, whereas others have reduced or no activity. The analyses of HLF‐Hyb variants revealed a strong impact of the central globular domain on activity. Our results indicate a comparable mode of action of hirudins and thrombin‐inhibiting HLF variants. Finally, we propose and discuss criteria for classifying hirudins and HLFs.

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Section: Discussionmentioning

confidence: 99%

Hirudin or hirudin‐like factor ‐ that is the question: insights from the analyses of natural and synthetic HLF variants

et al. 2019

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“…1 An anticoagulant extract was isolated from these leeches in 1903 for which the name hirudin was suggested. 3 At that time, the structure of the anticoagulant was unknown, but it was presumed to be a protein.…”

Section: Hirudinmentioning

confidence: 99%

“…1 This finding subsequently led to the development of hirudin, which was initially extracted from leeches and later obtained via rDNA technology. [2][3][4][5] The second observation, made in 1956 by Bettelheim, was that fibrinopeptide A, a small peptide released from fibrinogen by the action of thrombin, inhibited thrombin activity. 6 The third key event in the development of DTIs was the elucidation of the 3-dimensional structure of thrombin, first through molecular modeling and then by x-ray crystallographic analysis of thrombin and the hirudin/thrombin complex in 1989 and 1990, respectively.…”

mentioning

confidence: 99%

Translational Success Stories

Coppens

Eikelboom

Gustafsson

et al. 2012

Circulation Research

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ReviewTranslational Success Stories highlight how basic discoveries have led to clinical advances (such as the use of new drugs or diagnostic modalities in patients). This initiative reflects the renewed emphasis of our journal on translational research. It is hoped that these articles will stimulate efforts to translate basic insights into clinical practice. Translational Success Stories Development of Direct Thrombin InhibitorsMichiel Coppens, John W. Eikelboom, David Gustafsson, Jeffrey I. Weitz, Jack Hirsh Abstract: Anticoagulants are the cornerstone of therapy for conditions associated with arterial and venous thrombosis.Direct thrombin inhibitors (DTIs) are anticoagulants that bind to thrombin and block its enzymatic activity. The bivalent parenteral DTIs hirudin and bivalirudin were based on the observation that the salivary extracts of medicinal leeches prevented blood from clotting. Key events that facilitated the subsequent development of small molecule active site inhibitors, such as argatroban, were the observation that fibrinopeptide A had antithrombotic properties and determination of the crystal structure of thrombin. Hirudin and argatroban have found their niche for the treatment of patients with heparin-induced thrombocytopenia, whereas bivalirudin is approved as an alternative to heparin for patients undergoing percutaneous coronary intervention. The development of orally active direct thrombin inhibitors was challenging because of the need to convert water-soluble, poorly absorbable, active site inhibitors into fat-soluble prodrugs that were then transformed back to the active drug after intestinal absorption. Dabigatran etexilate was the first new oral anticoagulant to be approved for long-term anticoagulant treatment in 6 decades. This Review highlights the development of DTIs as a translational success story; an example in which the combination of scientific ingenuity, structure-based design, and rigorous clinical trials has created a new class of anticoagulants that has improved patient care. (Circ Res. 2012;111:920-929.) Key Words: thrombin Ⅲ anticoagulant Ⅲ drug development D irect thrombin inhibitors (DTIs) are anticoagulants that bind directly to thrombin and block its activity. Prior to their development, the injectable anticoagulants in clinical use were heparin and low-molecular-weight heparins (LMWHs). Both are classified as indirect inhibitors because they have no intrinsic activity; instead, they produce their anticoagulant effect by activating antithrombin. The only class of oral anticoagulants that was available at that time was the vitamin K antagonists (VKAs), such as warfarin.Several key events led to the development of DTIs. The first was the observation in 1884 that salivary secretions of the medicinal leech, Hirudo medicinalis, prevented blood from clotting. 1 This finding subsequently led to the development of hirudin, which was initially extracted from leeches and later obtained via rDNA technology. [2][3][4][5] The second observation, made in 1956 by Bettelheim, was th...

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“…Nach weiteren In-vitro-Studien (18,29,51) wurde die erste parenterale Antikoagulation 1909 bei Frauen vorgenommen, die an Eklampsie litten (21). Sie erhielten kommerzielles »Hirudin« (Sachse und Co., Deutschland), das aus einem einfachen Blutegelextrakt bestand.…”

Section: Pharmakologieunclassified

Hirudine zur Behandlung der heparininduzierten Thrombozytopenie und zur Thromboseprophylaxe

Lübenow¹,

Greinacher²

2002

Hamostaseologie

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ZusammenfassungDie in Deutschland zugelassenen Indikationen für die rekombinanten Hirudine Lepirudin (Refludan®) und Desirudin (Revasc®) sind Therapie der heparininduzierten Thrombozytopenie (HIT) bzw. Thromboseprophylaxe nach knie- oder hüftendoprothetischem Eingriff. Besonderheiten dieser Pharmaka sind ihre stark nierenabhängige Pharmakokinetik und ihre Fähigkeit, gegen Hirudin gerichtete Antikörper zu induzieren. Enges Monitoring der Dosis gestattet jedoch die sichere und effektive Anwendung. Während Lepirudin neben Danaparoid einen festen Platz bei der Behandlung der HIT einnimmt, konnte sich Desirudin zur Thromboseprophylaxe nach knie- oder hüftendoprothetischen Eingriffen bisher nicht durchsetzen.

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Ueber den die Blutgerinnung auf hebenden Bestandtheil des medicinischen Blutegels

Cited by 44 publications

References 3 publications

Hirudin or hirudin‐like factor ‐ that is the question: insights from the analyses of natural and synthetic HLF variants

Hirudin or hirudin‐like factor ‐ that is the question: insights from the analyses of natural and synthetic HLF variants

Translational Success Stories

Hirudine zur Behandlung der heparininduzierten Thrombozytopenie und zur Thromboseprophylaxe

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