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Small Molecules Selectively Targeting Sigma-1 Receptor for the Treatment of Neurological Diseases
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-10-28 , DOI: 10.1021/acs.jmedchem.0c01192
Na Ye 1 , Wangzhi Qin 1 , Sheng Tian 1 , Qingfeng Xu 1 , Eric A Wold 2 , Jia Zhou 2 , Xue-Chu Zhen 1
Affiliation  

The sigma-1 (σ1) receptor, an enigmatic protein originally classified as an opioid receptor subtype, is now understood to possess unique structural and functional features of its own and play critical roles to widely impact signaling transduction by interacting with receptors, ion channels, lipids, and kinases. The σ1 receptor is implicated in modulating learning, memory, emotion, sensory systems, neuronal development, and cognition and accordingly is now an actively pursued drug target for various neurological and neuropsychiatric disorders. Evaluation of the five selective σ1 receptor drug candidates (pridopidine, ANAVEX2-73, SA4503, S1RA, and T-817MA) that have entered clinical trials has shown that reaching clinical approval remains an evasive and important goal. This review provides up-to-date information on the selective targeting of σ1 receptors, including their history, function, reported crystal structures, and roles in neurological diseases, as well as a useful collation of new chemical entities as σ1 selective orthosteric ligands or allosteric modulators.

中文翻译:


选择性靶向 Sigma-1 受体的小分子治疗神经系统疾病



sigma-1 (σ 1 ) 受体是一种神秘的蛋白质,最初被归类为阿片受体亚型,现在被认为拥有其独特的结构和功能特征,并通过与受体、离子通道相互作用,在广泛影响信号转导方面发挥着关键作用。 、脂质和激酶。 σ 1受体涉及调节学习、记忆、情绪、感觉系统、神经元发育和认知,因此现在是各种神经系统和神经精神疾病的积极研究的药物靶点。对已进入临床试验的五种选择性σ1受体候选药物(普利多匹定、ANAVEX2-73、SA4503、S1RA和T-817MA)的评估表明,获得临床批准仍然是一个难以回避的重要目标。这篇综述提供了有关 σ 1受体选择性靶向的最新信息,包括它们的历史、功能、报道的晶体结构和在神经系统疾病中的作用,以及作为 σ 1选择性正位配体的新化学实体的有用整理或变构调节剂。
更新日期:2020-12-24
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