GluN2A选择性负变构调节剂结构基础的研究进展
Advances in the Structural Basis of GluN2A-Selective Negative Allosteric Modulators.
作者信息
Li Yinlong, Yuan Hongjie, Liang Steven H
机构信息
Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States.
Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, Georgia 30322, United States.
出版信息
ACS Med Chem Lett. 2025 May 9;16(6):911-915. doi: 10.1021/acsmedchemlett.5c00226. eCollection 2025 Jun 12.
-Methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels that play a critical role in synaptic plasticity, learning, and memory in the central nervous system (CNS). These receptors assemble into functionally diverse complexes composed of GluN1, GluN2, and GluN3 subunits. Among them, GluN1/GluN2A is expressed predominantly in adult brain, and its dysfunction has been implicated in various neuropathological conditions. Recent advances have identified several GluN2A-targeted agents, including highly selective negative allosteric modulators (NAMs). Structure-activity relationship (SAR) studies of existing agents have provided valuable insights into structural modifications that enhance pharmacological properties, offering promising avenues for therapeutic development.
N-甲基-D-天冬氨酸受体（NMDARs）是配体门控离子通道，在中枢神经系统（CNS）的突触可塑性、学习和记忆中起关键作用。这些受体组装成由GluN1、GluN2和GluN3亚基组成的功能多样的复合物。其中，GluN1/GluN2A主要在成人大脑中表达，其功能障碍与多种神经病理状况有关。最近的进展已经鉴定出几种靶向GluN2A的药物，包括高度选择性负变构调节剂（NAMs）。现有药物的构效关系（SAR）研究为增强药理特性的结构修饰提供了有价值的见解，为治疗开发提供了有前景的途径。
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