Discovery of triazoloquinoxaline as novel STING agonists via structure-based virtual screening
Discovery of triazoloquinoxaline as novel STING agonists via structure-based virtual screening
复制标题
通过基于结构的虚拟筛选发现三唑喹喔啉作为新型 STING 激动剂
DOI：
10.1016/j.bioorg.2020.103958
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发表时间：
2020-07-01
影响因子：
5.1
通讯作者：
Zheng, Mingyue
中科院分区：
文献类型：
--
作者：
Hou, Hui;Yang, Ruirui;Zheng, Mingyue
Stimulator of interferon genes (STING) is an endoplasmic reticulum adaptor facilitating innate immune signaling. Activation of STING leads to expression of interferons (IFNs) and pro-inflammatory cytokines which is associated with antiviral and antitumor responses. It is imperative to discovery potent compounds that precisely modulate STING. Herein, we describe the discovery of triazoloquinoxaline1aas a novel STING agonist via Structure-based Virtual Screening. Specifically, biochemical and cell-based assays suggested that1astimulated concentration-dependently mRNA expression of IFNβ, CXCL-10 and IL-6. Furthermore,1asignificantly induced phosphorylation of STING, TANK-binding kinases1 (TBK1) and interferon regulatory factor 3 (IRF3), suggesting the activation of STING and its downstream TBK1-IRF3 signaling axis. In addition,1aactivated secretion of secreted alkaline phosphatase (SEAP) in dose-dependent manner and EC50was 16.77 ± 3.814 μM, which is comparable with EC50of 2′3′-cGAMP (9.212 ± 2.229 μM). These studies revealed that1ais a promising STING agonist possessing the potential to be further developed for antiviral and antitumor treatment.
