Tropmann, Katharina and Hoering, Carina and Plank, Nicole and Pockes, Steffen (2020) Discovery of a G Protein-Biased Radioligand for the Histamine H-2 Receptor with Reversible Binding Properties. JOURNAL OF MEDICINAL CHEMISTRY, 63 (21). pp. 13090-13102. ISSN 0022-2623, 1520-4804
Full text not available from this repository. (Request a copy)Abstract
Currently employed histamine H-2 receptor (H2R) radioligands possess several drawbacks, for example, high nonspecificity, insurmountable binding, or short half-life. We report the synthesis and the chemical and pharmacological characterization of the highly stable carbamoylguanidine-type radioligand [H-3]UR-KAT479 ([H-3]23), a subtype selective histamine H-2 receptor G protein-biased agonist. [H-3]23 was characterized by saturation, kinetic, and competition binding assays at the human, guinea pig, and mouse H-2 receptors (co-)expressed in HEK293(T) cells. [H-3]23 reversibly bound to the respective H(2)Rs with moderate to high affinity (human/guinea pig/mouse Kd: 24/28/94 nM). In order to investigate the applicability of carbamoylguanidine-type ligands in animal studies elucidating the role of the H2R in the brain, we performed a preliminary partitioning experiment in the whole human/mouse blood, which indicated a low binding of [H-3]23 to red blood cells. These properties turn [H-3]23 into a powerful tool for the determination of binding affinities and demonstrate the promising pharmacokinetic profile of carbamoylguanidine-type ligands.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2021 08:15 |
| Last Modified: | 08 Mar 2021 08:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43381 |
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