STING inhibitors and degraders: Potential therapeutic agents in inflammatory diseases

IF 6 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry Pub Date : 2025-04-15 DOI:10.1016/j.ejmech.2025.117632

Kerong Wu , Yiwen Xu , Peizhao Liu , Kexin Chen , Yun Zhao

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Abstract

The regulation of the STING (stimulator of interferon genes) pathway represents a promising target for a range of inflammatory diseases. This review provides an overview of the structure of STING and discusses the mechanisms by which the cyclic GMP-AMP synthase (cGAS)-STING pathway is associated with various autoinflammatory and autoimmune diseases. We explore how targeting STING inhibition or degradation can alleviate excessive inflammatory signaling and improve efficacy. Emerging strategies include inhibiting STING expression by covalently binding compounds or using ligands that target the binding pocket. In addition, selective degradation of STING via the ubiquitin-proteasome system or the lysosomal pathway shows promise. In addition, we explore the implications of modulating the cGAS-STING pathway in the context of various inflammatory diseases. Finally, we summarize the chemical properties of recently developed STING compounds and their potential clinical applications. By comprehensively reviewing the current understanding of the role of STING in inflammation and the therapeutic potential of targeting STING, we aim to identify new avenues of intervention that could improve outcomes for patients with inflammatory diseases. This review highlights the important role of STING in the regulation of inflammation and its potential as a target for innovative therapeutic strategies.

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STING抑制剂和降解剂：炎症性疾病的潜在治疗剂

STING（干扰素基因刺激因子）通路的调控是一系列炎症性疾病的一个有希望的靶点。本文综述了STING的结构，并讨论了环GMP-AMP合成酶(cGAS)-STING通路与各种自身炎症和自身免疫性疾病相关的机制。我们探索如何靶向STING抑制或降解可以减轻过度的炎症信号并提高疗效。新兴的策略包括通过共价结合化合物或使用靶向结合袋的配体来抑制STING表达。此外，通过泛素-蛋白酶体系统或溶酶体途径选择性降解STING显示出希望。此外，我们探讨了在各种炎症性疾病的背景下调节cGAS-STING通路的意义。最后，我们总结了近年来开发的STING化合物的化学性质及其潜在的临床应用。通过全面回顾目前对STING在炎症中的作用以及靶向STING的治疗潜力的理解，我们旨在确定新的干预途径，以改善炎症性疾病患者的预后。这篇综述强调了STING在炎症调节中的重要作用及其作为创新治疗策略靶点的潜力。

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来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.