具有自噬调节能力的共价抑制剂：绘制药物设计和发现的新途径。

IF 6.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Discovery Today Pub Date : 2025-04-01 DOI:10.1016/j.drudis.2025.104347

Yutong Wang , Shiyu Luo , Hongbao Sun , Shuai Huang , Lianhai Shan , Jifa Zhang

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引用次数: 0

摘要

自噬是降解受损细胞器和维持细胞稳态的重要细胞过程。通过与特定蛋白形成不可逆的键，共价抑制剂在调节自噬及其相关途径方面具有明显的优势。这些抑制剂可以在较低剂量下持续调节自噬，提高治疗效果，同时最大限度地减少不良反应。我们讨论了它们的机制，包括它们如何影响自噬相关的酶和途径，以及它们在治疗癌症和其他自噬相关疾病中的潜在应用。研究自噬相关通路靶点将为共价抑制剂的开发提供新的见解，并增强复杂疾病的治疗策略。

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Covalent inhibitors possessing autophagy-modulating capabilities: charting novel avenues in drug design and discovery

Autophagy is a crucial cellular process in degrading damaged organelles and maintaining cellular homeostasis. By forming irreversible bonds with specific proteins, covalent inhibitors present a distinct advantage in regulating autophagy and its related pathways. These inhibitors can provide sustained modulation of autophagy at lower doses, improving therapeutic efficacy while minimizing adverse effects. We discuss their mechanisms, including how they affect autophagy-related enzymes and pathways, and their potential applications in the treatment of cancers and other autophagy-related disorders. Studying autophagy-related pathway targets will provide new insights for the development of covalent inhibitors and enhance therapeutic strategies for complex conditions.

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来源期刊

Drug Discovery Today 医学-药学

CiteScore

14.80

自引率

2.70%

发文量

293

审稿时长

6 months

期刊介绍： Drug Discovery Today delivers informed and highly current reviews for the discovery community. The magazine addresses not only the rapid scientific developments in drug discovery associated technologies but also the management, commercial and regulatory issues that increasingly play a part in how R&D is planned, structured and executed. Features include comment by international experts, news and analysis of important developments, reviews of key scientific and strategic issues, overviews of recent progress in specific therapeutic areas and conference reports.