结构导向方法调节内体toll样受体TLR7、TLR8和TLR9：进展、挑战和治疗前景

IF 7.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Discovery Today Pub Date : 2025-10-07 DOI:10.1016/j.drudis.2025.104495

Troy Matziol, Valerij Talagayev, Günther Weindl, Gerhard Wolber

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引用次数: 0

摘要

TLR7， TLR8和TLR9是抗病毒防御，自身免疫和癌症免疫治疗的核心内体免疫受体。最近的结构见解揭示了不同的配体结合机制和构象动力学，使设计选择性小分子激动剂和拮抗剂成为可能。本文综述了TLR7/8/9在生物学、药理学和结构导向药物发现方面的主要进展。我们强调临床进展、递送策略和转化挑战，包括物种特异性差异和免疫相关毒性。纳米粒子系统和内源性RNA模拟物等新方法有望靶向调节TLR活性。总之，这些发展强调了TLR精确调节在免疫复杂疾病中的治疗潜力。

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Structure-guided approaches to modulate endosomal Toll-like receptors TLR7, TLR8 and TLR9: advances, challenges and therapeutic promise.

TLR7, TLR8 and TLR9 are endosomal immune receptors central to antiviral defense, autoimmunity and cancer immunotherapy. Recent structural insights have revealed distinct ligand-binding mechanisms and conformational dynamics, enabling the design of selective small-molecule agonists and antagonists. This review summarizes key advances in TLR7/8/9 biology, pharmacology and structure-guided drug discovery. We highlight clinical progress, delivery strategies and translational challenges including species-specific differences and immune-related toxicities. Novel approaches such as nanoparticle systems and endogenous RNA mimetics promise targeted modulation of TLR activity. Together, these developments emphasize the therapeutic potential of precision TLR modulation in immunologically complex diseases.

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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.