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A Versatile Sub-Nanomolar Fluorescent Ligand Enables NanoBRET Binding Studies and Single-Molecule Microscopy at the Histamine H3 Receptor

Rosier, Niklas ; Grätz, Lukas ; Schihada, Hannes ; Möller, Jan ; Işbilir, Ali ; Humphrys, Laura J. ; Nagl, Martin ; Seibel, Ulla ; Lohse, Martin J. ; Pockes, Steffen


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 ...


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