Rosier, Niklas and Graetz, Lukas and Schihada, Hannes and Moeller, Jan and Isbilir, Ali and Humphrys, Laura J. and Nagl, Martin and Seibel, Ulla and Lohse, Martin J. and Pockes, Steffen (2021) A Versatile Sub-Nanomolar Fluorescent Ligand Enables NanoBRET Binding Studies and Single-Molecule Microscopy at the Histamine H-3 Receptor. JOURNAL OF MEDICINAL CHEMISTRY, 64 (15). pp. 11695-11708. ISSN 0022-2623, 1520-4804
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGHLY POTENT; GPCR LIGANDS; H-2-RECEPTOR; ANTAGONISTS; ASSAY; INHIBITION; RELEASE; SURFACE; TOOLS; RAT; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 07:05 |
| Last Modified: | 13 Sep 2022 07:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47265 |
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