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环鸟苷酸-干扰素基因刺激物(cGAS-STING)通路中的蛋白-蛋白相互作用:药物化学视角。

Protein-protein interactions in cGAS-STING pathway: a medicinal chemistry perspective.

机构信息

State Key Laboratory of Natural Medicines, Jiang Su Key Laboratory of Drug Design & Optimization, China Pharmaceutical University, Nanjing, 210009, China.

Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.

出版信息

Future Med Chem. 2024;16(17):1801-1820. doi: 10.1080/17568919.2024.2383164. Epub 2024 Sep 12.

Abstract

Protein-protein interactions (PPIs) play pivotal roles in biological processes and are closely linked with human diseases. Research on small molecule inhibitors targeting PPIs provides valuable insights and guidance for novel drug development. The cGAS-STING pathway plays a crucial role in regulating human innate immunity and is implicated in various pathological conditions. Therefore, modulators of the cGAS-STING pathway have garnered extensive attention. Given that this pathway involves multiple PPIs, modulating PPIs associated with the cGAS-STING pathway has emerged as a promising strategy for modulating this pathway. In this review, we summarize an overview of recent advancements in medicinal chemistry insights into cGAS-STING PPI-based modulators and propose alternative strategies for further drug discovery based on the cGAS-STING pathway.

摘要

蛋白质-蛋白质相互作用(PPIs)在生物过程中发挥着关键作用,与人类疾病密切相关。针对 PPIs 的小分子抑制剂的研究为新药开发提供了有价值的见解和指导。cGAS-STING 途径在调节人体先天免疫中起着至关重要的作用,并与多种病理状况有关。因此,cGAS-STING 途径的调节剂受到了广泛关注。鉴于该途径涉及多个 PPIs,调节与 cGAS-STING 途径相关的 PPIs 已成为调节该途径的一种有前途的策略。在这篇综述中,我们总结了基于 cGAS-STING PPI 的调节剂的化学生物学研究的最新进展,并基于 cGAS-STING 途径提出了进一步药物发现的替代策略。

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本文引用的文献

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Development of LB244, an Irreversible STING Antagonist.LB244 的研发:一种不可逆转的 STING 拮抗剂。
J Am Chem Soc. 2023 Sep 20;145(37):20273-20288. doi: 10.1021/jacs.3c03637. Epub 2023 Sep 11.
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Non-cell-autonomous cancer progression from chromosomal instability.非细胞自主性的染色体不稳定性癌症进展。
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Targeting STING oligomerization with small-molecule inhibitors.靶向 STING 寡聚化的小分子抑制剂。
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Science. 2023 Aug 4;381(6657):508-514. doi: 10.1126/science.adf8974. Epub 2023 Aug 3.

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