Peptidomimetic thrombin inhibitors
Drug development review published in Pathophysiol Haemost Thromb (2005)
Abstract
The central position of thrombin in the coagulation cascade has made it a popular target for discovery of novel antithrombotic agents. Starting with hirudin, a natural peptide isolated from the medicinal leech, its shorter synthetic analogue hirulog, and argatroban,the first therapeutically used synthetic small-molecule thrombin active site inhibitor, hundreds of direct thrombin inhibitors have been discovered over the last 20 years. Most of them are peptidomimetic compounds,based on the amino acid sequence of fibrinogen which binds into the thrombin active site. Since elucidation of the crystal structure of human thrombin in 1989, the structure-based design of low-molecular-weight peptidomimetic thrombin inhibitors has been greatly aided by the use of x-ray crystallographic analysis of thrombin-inhibitor complexes. The ultimate goal of most research programmes and drug optimization strategies is to develop an orally bioavailable, small-molecule,direct thrombin inhibitor that would be suitable for once or twice daily dosing. An overview of the most advanced peptidomimetic direct thrombin inhibitors bivalirudin, argatroban, ximelagatran and dabigatran is presented.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Reviews the development of direct thrombin inhibitors starting from leech-derived hirudin and its synthetic peptidomimetic descendants — hirulog, argatroban, bivalirudin, ximelagatran, dabigatran — culminating in orally bioavailable small-molecule scaffolds.
Warum dies für die Hirudotherapie relevant ist
This review surveys peptidomimetic direct thrombin inhibitors, tracing the field from hirudin, a natural peptide isolated from the medicinal leech, and related synthetic analogues such as hirulog, to small-molecule inhibitors including bivalirudin, argatroban, ximelagatran, and dabigatran. It emphasizes structure-based design informed by thrombin crystal structures and the goal of developing orally bioavailable direct thrombin inhibitors. This is relevant to ASH because it documents how a leech-derived molecule helped seed a major class of antithrombotic drug discovery. The caveat is that the article is a medicinal-chemistry review focused on synthetic inhibitors, not on leech therapy, the live leech secretome, or clinical hirudotherapy outcomes.
Zitation
Peptidomimetic thrombin inhibitors.
Kikelj D · Pathophysiology of haemostasis and thrombosis, 2005
Verwandter klinischer Kontext
Erfahren Sie, wie diese Forschung mit der klinischen Praxis verknüpft ist
Zur ASH-Bibliothek hinzugefügt: May 26, 2026 · Letzte Aktualisierung der Website: June 18, 2026