SR-717 是一种非核苷酸 STING 激动剂，在 ISG-THP1 (WT) 和 ISG-THP1 cGAS KO (cGAS KO) 细胞系中的 EC50 分别为 2.1 μM 和 2.2 μM。
SR-717 is a stable cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) mimetic, Antitumor activity[1]. The cGAS-STING pathway promotes the senescence of cancer cells, induces apoptosis of cancer cells, and increases the protective effect of cytotoxic T cells and natural killer cell-mediated cytotoxicity[4]. cGAS-STING pathway plays an important role in the chronic inflammatory status in various organs[5].SR-717 as a non-nucleotide STING agonist with EC50s of 2.1 μM and 2.2 μM in ISG-THP1 (WT) and ISG-THP1 cGAS KO (cGAS KO) cell lines, respectively.
Pharmacological targeting of cGAS/STING-YAP signaling by both a small-molecule STING agonist, SR-717 that blocks the profibrotic activity of endothelial YAP, attenuated liver and kidney fibrosis[2].
By STING agonist SR-717, activation of cGAS-STING pathway induced increased apoptosis, inflammation, and oxidative stress via regulating ERS and therefore resulted in pulmonary edema and pathological injury in the lungs of I/R rats[3].
参考文献:
[1]: Chin EN, Yu C, et,al. Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic. Science. 2020 Aug 21;369(6506):993-999. doi: 10.1126/science.abb4255. PMID: 32820126.
[2]: Wang L, Zhang Y, et,al. Pharmacological targeting of cGAS/STING-YAP axis suppresses pathological angiogenesis and ameliorates organ fibrosis. Eur J Pharmacol. 2022 Sep 2;932:175241. doi: 10.1016/j.ejphar.2022.175241. Epub ahead of print. PMID: 36058291.
[3]: Huang R, Shi Q, et,al. Inhibition of the cGAS-STING Pathway Attenuates Lung Ischemia/Reperfusion Injury via Regulating Endoplasmic Reticulum Stress in Alveolar Epithelial Type II Cells of Rats. J Inflamm Res. 2022 Sep 5;15:5103-5119. doi: 10.2147/JIR.S365970. PMID: 36091334; PMCID: PMC9462969.
[4]: Du H, Xu T, et,al. cGAS-STING signaling in cancer immunity and immunotherapy. Biomed Pharmacother. 2021 Jan;133:110972. doi: 10.1016/j.biopha.2020.110972. Epub 2020 Nov 27. PMID: 33254021.
[5]: Bao T, Liu J, et,al. The cGAS-STING pathway: more than fighting against viruses and cancer. Cell Biosci. 2021 Dec 14;11(1):209. doi: 10.1186/s13578-021-00724-z. PMID: 34906241; PMCID: PMC8670263.
SR-717 是一种稳定的环磷酸鸟苷-磷酸腺苷 (cGAMP) 模拟物，具有抗肿瘤活性[1]。 cGAS-STING通路促进癌细胞衰老，诱导癌细胞凋亡，增加细胞毒性T细胞和自然杀伤细胞介导的细胞毒性的保护作用[4]。 cGAS-STING通路在多种器官的慢性炎症状态中起着重要作用[5]。SR-717作为一种非核苷酸STING激动剂，在ISG-THP1中的EC50分别为2.1 μM和2.2 μM（ WT)和ISG-THP1 cGAS KO (cGAS KO)细胞系。
小分子 STING 激动剂 SR-717 对 cGAS/STING-YAP 信号的药理学靶向作用可阻断内皮 YAP 的促纤维化活性，减轻肝肾纤维化[2]。< /p>\n
通过 STING 激动剂 SR-717，cGAS-STING 通路的激活通过调节 ERS 诱导细胞凋亡、炎症和氧化应激增加，从而导致 I/R 大鼠肺部的肺水肿和病理损伤[3 ].
| Cell experiment [1]: | |
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Cell lines |
human umbilical vein endothelial cells (HUVECs) |
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Preparation Method |
The cells were exposed to 2 μM SR-717 and challenged with 10% fetal bovine serum (FBS) for 2 h. |
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Reaction Conditions |
2 μM SR-717 for two hours |
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Applications |
Pharmacological targeting of cGAS/STING-YAP signaling by both a small-molecule STING agonist, SR-717 that blocks the profibrotic activity of endothelial YAP, attenuated liver and kidney fibrosis. |
| Animal experiment [2]: | |
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Animal models |
Stinggt/gt mice |
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Preparation Method |
The tumor growth was detected by intraperitoneal injection of SR-717 (30 mg/kg, once a day, for 1 week). |
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Dosage form |
30 mg/kg SR-717 once-per-day for 1 week |
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Applications |
SR-717 (30 mg/kg intraperitoneally for 7 days) displays antitumor activity; promots the activation of CD8+ T, natural killer, and dendritic cells in relevant tissues; and facilitates antigen cross-priming |
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参考文献: [1]. Wang L, Zhang Y, et,al. Pharmacological targeting of cGAS/STING-YAP axis suppresses pathological angiogenesis and ameliorates organ fibrosis. Eur J Pharmacol. 2022 Sep 2;932:175241. doi: 10.1016/j.ejphar.2022.175241. Epub ahead of print. PMID: 36058291. [2]. Chin EN, Yu C, et,al. Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic. Science. 2020 Aug 21;369(6506):993-999. doi: 10.1126/science.abb4255. PMID: 32820126. |
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