20S蛋白酶体增强的最新进展：不可药物靶标的降解

IF 4 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2025-09-19 DOI:10.1021/acsmedchemlett.5c00451

Sydney G. Cobb, and , Jetze J. Tepe*,

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引用次数: 0

摘要

泛素非依赖性蛋白酶体系统已成为多种疾病，包括神经退行性疾病的一个有吸引力的干预点。虽然对这一系统的抑制已经研究了几十年，相比之下，20S蛋白酶体的增强要年轻得多，但在这一领域取得了实质性的进展，特别是在过去的五年里。这一微观视角将突出这些进步，重点关注在设计强效增强剂和在疾病相关系统中评估它们方面正在取得的新进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Recent Advancements in 20S Proteasome Enhancement: Degradation of Undruggable Targets

The ubiquitin-independent proteasome system has emerged as an attractive point of intervention for a variety of diseases, including neurodegenerative diseases. Though inhibition of this system has been studied for decades, 20S proteasome enhancement is much younger by comparison, but substantial levels of progress have been made in this field especially within the last five years. This microperspective will highlight these advancements, focusing on the novel developments being made in designing potent enhancers and evaluating them in disease-relevant systems.

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.