The xanthone derivate 5′,6′‐dimethylxanthenone‐4‐acetic acid (DMXAA, also known as ASA404 or vadimezan) is a potent agonist of murine STING (stimulator of interferon genes), but cannot activate human STING. Herein we report that α‐mangostin, which bears the xanthone skeleton, is an agonist of human STING, but activates murine STING to a lesser extent. Biochemical and cell‐based assays indicate that α‐mangostin binds to and activates human STING, leading to activation of the downstream interferon regulatory factor (IRF) pathway and production of type I interferons. Furthermore, our studies show that α‐mangostin has the potential to repolarize human monocyte‐derived M2 macrophages to the M1 phenotype. The agonist effect of α‐mangostin in the STING pathway might account for its antitumor and antiviral activities.

中文翻译：

---

鉴定α-Mangostin作为人类STING的激动剂。

an吨酮衍生物5'，6'-二甲基黄嘌呤-4-乙酸（DMXAA，也称为ASA404或vadimezan）是鼠STING（干扰素基因的刺激物）的有效激动剂，但不能激活人STING。本文中我们报道，带有黄嘌呤骨架的α-Mangostin是人类STING的激动剂，但对小鼠STING的激活程度较小。生化和基于细胞的分析表明，α-Mangostin结合并激活人类STING，导致下游干扰素调节因子（IRF）途径的激活和I型干扰素的产生。此外，我们的研究表明，α-Mangostin具有将人类单核细胞衍生的M2巨噬细胞重新极化为M1表型的潜力。α-Mangostin在STING途径中的激动作用可能是其抗肿瘤和抗病毒活性的原因。