Rosier, Niklas ; Grätz, Lukas ; Schihada, Hannes 
; Möller, Jan ; Işbilir, Ali ; Humphrys, Laura J. ; Nagl, Martin ; Seibel, Ulla ; Lohse, Martin J. ; Pockes, Steffen
Alternative Links zum Volltext:DOIVerlag
| Dokumentenart: | Artikel |
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| Titel eines Journals oder einer Zeitschrift: | Journal of Medicinal Chemistry |
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| Verlag: | AMER CHEMICAL SOC |
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| Ort der Veröffentlichung: | WASHINGTON |
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| Band: | 64 |
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| Nummer des Zeitschriftenheftes oder des Kapitels: | 15 |
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| Seitenbereich: | S. 11695-11708 |
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| Datum: | 2021 |
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| Institutionen: | Chemie und Pharmazie > Institut für Pharmazie |
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| Identifikationsnummer: | | Wert | Typ |
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| 10.1021/acs.jmedchem.1c01089 | DOI |
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| Stichwörter / Keywords: | HIGHLY POTENT; GPCR LIGANDS; H-2-RECEPTOR; ANTAGONISTS; ASSAY; INHIBITION; RELEASE; SURFACE; TOOLS; RAT; |
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| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie |
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| Status: | Veröffentlicht |
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| Begutachtet: | Ja, diese Version wurde begutachtet |
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| An der Universität Regensburg entstanden: | Ja |
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| Dokumenten-ID: | 51108 |
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Web of Science
Zusammenfassung
The histamine H-3 receptor (H3R) is considered an attractive drug target for various neurological diseases. We here report the synthesis of UR-NR266, a novel fluorescent H3R ligand. Broad pharmacological characterization revealed UR-NR266 as a sub-nanomolar compound at the H3R with an exceptional selectivity profile within the histamine receptor family. The presented neutral antagonist showed ...
Zusammenfassung
The histamine H-3 receptor (H3R) is considered an attractive drug target for various neurological diseases. We here report the synthesis of UR-NR266, a novel fluorescent H3R ligand. Broad pharmacological characterization revealed UR-NR266 as a sub-nanomolar compound at the H3R with an exceptional selectivity profile within the histamine receptor family. The presented neutral antagonist showed fast association to its target and complete dissociation in kinetic binding studies. Detailed characterization of standard H3R ligands in NanoBRET competition binding using UR-NR266 highlights its value as a versatile pharmacological tool to analyze future H3R ligands. The low nonspecific binding observed in all experiments could also be verified in TIRF and confocal microscopy. This fluorescent probe allows the highly specific analysis of native H3R in various assays ranging from optical high throughput technologies to biophysical analyses and single-molecule studies in its natural environment. An off-target screening at 14 receptors revealed UR-NR266 as a selective compound.
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