发现了一种新的基于四氢喹啉的STING抑制剂，具有抗急性肾损伤的体内疗效
Discovery of a New Tetrahydroquinoline-Based Chemotype for STING Inhibition with In Vivo Efficacy against Acute Kidney Injury.
摘要(中文译文)
干扰素基因刺激因子（STING）的异常激活可驱动过度的I型干扰素及炎症反应，参与自身免疫性和炎症性疾病（包括急性肾损伤，AKI）的发病。在此，我们报道发现了一种以四氢喹啉为骨架的STING抑制剂化学型，以 为代表，拓展了当前小分子STING抑制剂有限的骨架多样性。机制研究表明， 通过一种非经典的、可能为变构的结合模式与STING结合，并实现持续性的靶点占据。 在鼠源和人源细胞中均能强效抑制STING依赖性信号传导，并减少I型干扰素及促炎细胞因子的产生。在顺铂诱导的AKI小鼠模型中， 减轻了肾脏和肝脏损伤，并下调了STING相关炎症基因的表达。这些发现确立了四氢喹啉骨架作为开发下一代STING抑制剂的有前景的基础，该类抑制剂具有替代性靶点结合模式，可用于治疗STING驱动的炎症性疾病。
Abstract
Aberrant activation of the stimulator of interferon genes (STING) drives excessive type I interferon and inflammatory responses implicated in autoimmune and inflammatory diseases, including acute kidney injury (AKI). Here, we report the discovery of a tetrahydroquinoline-based STING inhibitor chemotype, represented by , that expands the limited scaffold diversity of current small-molecule STING inhibitors. Mechanistic studies suggest that engages STING through a noncanonical, likely allosteric, binding mode with sustained target engagement. potently suppressed STING-dependent signaling and reduced type I interferon and pro-inflammatory cytokine production in both murine and human cells. In a cisplatin-induced AKI mouse model, attenuated renal and hepatic injury and down-regulated STING-associated inflammatory gene expression. These findings establish the tetrahydroquinoline scaffold as a promising foundation for the development of next-generation STING inhibitors with alternative target engagement modes for the treatment of STING-driven inflammatory disorders.
如何引用
AMA
So Hyeon Jeong, Ji Hun Wi, Jiyoon Park, Yeseul Kim, Jinhee Mun, Hayeon Kim, et al. Discovery of a New Tetrahydroquinoline-Based Chemotype for STING Inhibition with In Vivo Efficacy against Acute Kidney Injury.. Journal of medicinal chemistry. 2026; doi:10.1021/acs.jmedchem.6c00162.
APA
So Hyeon Jeong, Ji Hun Wi, Jiyoon Park, Yeseul Kim, Jinhee Mun, Hayeon Kim, et al (2026). Discovery of a New Tetrahydroquinoline-Based Chemotype for STING Inhibition with In Vivo Efficacy against Acute Kidney Injury.. Journal of medicinal chemistry. https://doi.org/10.1021/acs.jmedchem.6c00162
GB/T 7714
So Hyeon Jeong, Ji Hun Wi, Jiyoon Park, Yeseul Kim, Jinhee Mun, Hayeon Kim, et al. Discovery of a New Tetrahydroquinoline-Based Chemotype for STING Inhibition with In Vivo Efficacy against Acute Kidney Injury.[J]. Journal of medicinal chemistry, 2026 doi:10.1021/acs.jmedchem.6c00162.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出