Fakulteta za farmacijo, Ljubljana (FFALJ)
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Thrombin receptor antagonists; Recent advances in PAR-1 antagonist developmentAnderluh, Marko ; Sollner Dolenc, MarijaThe receptor for the serine protease thrombin, the protease-activated receptor-1 (PAR-1), has been recently characterized. Its key roles in thrombin-stimulated human platelet activation, vascular ... endothelial and smoothmuscle proliferation, inflammatory responses and neurodegeneration suggest receptor involvement in various disorders such as arterial thrombosis,atherosclerosis, restenosis, inflammation and myocardial infarction. It has been established that thrombin elicits the majority of its effects via PAR-1. PAR-1 has a novel mechanism of activation. The receptor, a member of the seven-transmembrane domain receptor family, is cleaved by thrombin at a specific site on the N-terminal extension, and a newly exposed N-terminus acts as a tethered ligand to activate the receptor itself. The need for development of a PAR-1 antagonist that may be valuable as a therapeutic agent has been recognized. An intriguing challenge is the necessity of the antagonist to compete with an intramolecular ligand while showing no intrinsic activity. The lead compounds were found to be synthetic peptides containing N-terminal hexapeptide or pentapeptide (Ser-Phe-Leu-Leu-Arg- Asn, Ser-Phe-Leu-Leu-Arg) or modified sequences (TRAPsč thrombin receptor-activating peptides), which exhibit full PAR-1 agonist activity. Selective PAR-1 antagonists have already been synthesized. Though their potency is still not enough to justify therapeutic use, it is clear thatfuture progress will bring a novel class of drugs-thrombin receptor antagonists. The emphasis of this review, therefore, will be placed on advances in the discovery of potent and selective PAR-1 antagonists.Vir: Current medicinal chemistry. - ISSN 0929-8673 (Vol. 9, no. 13, 2002, str. 1229-1250)Vrsta gradiva - članek, sestavni delLeto - 2002Jezik - angleškiCOBISS.SI-ID - 1170289
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Sollner Dolenc, Marija | 08519 |
Vir: Osebne bibliografije
in: SICRIS
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