Sigma-2受体iboga衍生配体的发现

IF 3.8 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Bio & Med Chem Au Pub Date : 2025-05-12 DOI:10.1021/acsbiomedchemau.5c0001110.1021/acsbiomedchemau.5c00011

Alexander J. Hughes, Julie A. Talbert and Steven D. Townsend*,

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引用次数: 0

摘要

物质使用障碍（SUD）是一种影响人的大脑和行为的精神状况，导致对酒精、毒品和药物使用缺乏控制。缺乏有效和新颖的治疗SUD是一个日益关注的问题。因此，我们合成了一系列的伊博加生物碱衍生物，并评估了它们与一组基于cns的蛋白质的受体结合谱，这些蛋白质是在国家精神卫生研究所的精神活性药物筛选项目中进行的。这些研究揭示了两种对sigma-2受体具有高亲和力的化合物，并引入了iboga生物碱框架作为sigma-2配体发育的新支架。

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Discovery of Iboga-Derived Ligands for the Sigma-2 Receptor

Substance use disorder (SUD) is a mental condition that affects a person’s brain and behavior, leading to a lack of control with alcohol, drug, and medication use. The lack of efficacious and novel treatments for SUD is a growing concern. As such, we have synthesized a series of iboga alkaloid derivatives and evaluated their receptor binding profiles against a panel of CNS-based proteins, which were performed at the National Institute of Mental Health Psychoactive Drug Screening Program. These studies revealed two compounds that exhibit high affinity for the sigma-2 receptor and introduce the iboga alkaloid framework as a new scaffold for the development of sigma-2 ligands.

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来源期刊

ACS Bio & Med Chem Au 药物、生物、化学-

CiteScore

4.10

自引率

0.00%

发文量

期刊介绍： ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.