Mönnich Denise, Nagl Martin, Forster Lisa, Rosier Niklas, Igel Patrick, Pockes Steffen
Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany.
Department of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota 55414, United States.
ACS Med Chem Lett. 2023 Oct 17;14(11):1589-1595. doi: 10.1021/acsmedchemlett.3c00413. eCollection 2023 Nov 9.
Radioligands used previously for histamine H receptor (HR) are accompanied by a number of disadvantages. In this study, we report the synthesis of the new HR radioligand [H]UR-MN259 ([H]) with high (radio)chemical purity and stability. The radioligand exhibits sub-nanomolar affinity for the target receptor (p (HR) = 9.56) and displays an outstanding selectivity profile within the histamine receptor family (>100,000-fold selective). [H]UR-MN259 is ideally suitable for the characterization of HR ligands in competition binding and shows one-site binding to the HR in saturation binding experiments. The radiotracer shows fast association to the receptor (τ = 6.11 min), as well as full dissociation from the receptor (τ = 14.48 min) in kinetic binding studies. The distinguished profile of [H]UR-MN259 makes it a highly promising pharmacological tool to further investigate the role of the HR in the CNS.
先前用于组胺H受体（HR）的放射性配体存在许多缺点。在本研究中，我们报告了具有高（放射）化学纯度和稳定性的新型HR放射性配体[H]UR-MN259（[H]）的合成。该放射性配体对靶受体表现出亚纳摩尔亲和力（p（HR）= 9.56），并且在组胺受体家族中显示出出色的选择性（选择性>100,000倍）。[H]UR-MN259非常适合在竞争结合中表征HR配体，并且在饱和结合实验中显示出与HR的单点结合。在动力学结合研究中，该放射性示踪剂显示出与受体的快速结合（τ = 6.11分钟），以及从受体的完全解离（τ = 14.48分钟）。[H]UR-MN259的独特特性使其成为进一步研究HR在中枢神经系统中作用的极具前景的药理学工具。
