Stimulator of interferon genes (STING) is an endoplasmic reticulum signaling protein which has been demonstrated to play essential roles in antitumor immunity. SR-717 is a non-nucleotide, small-molecule STING agonist with an IC50 of 7.8 μM. Within the CD45.2+ population, SR-717 treatment resulted in a significant increase in the frequency of CD8 T cells among TILs (tumor infiltrating lymphocytes) and a decrease in the frequencies of NK cells within the draining lymphnode (dLN) and spleen. In WT C57BL/6 mice, SR-717 induced IFN-β after intraperitoneal administration in a dose-dependent manner. In WT or Stinggt/gt mice, a 30 mg/kg intraperitoneal once-per-day regimen of SR-717 for 1 week was found to maximally inhibit B16.F10 tumor growth. In C57BL/6 mice bearing B16.F10 cells, SR-717 (15 mg/kg; dosed intraperitoneally; once per day) significantly inhibited the formation of pulmonary nodules in this model of metastasis. SR-717 (30 mg/kg intraperitoneally) displayed a better level of efficacy than anti-PD-1 or anti-PD-L1 antibody therapy on reducing tumor burden and improving overall survival in the B16.F10 model[2].
作用机制
The structure of SR-717 facilitates a binding mode in which Thr263 side chain hydroxyls from both monomers are positioned to form hydrogen-bond interactions with SR-717[2].
SR-717 细胞实验
Cell Line
Concentration
Treated Time
Description
References
RAW264.7 cells
10.0 µM
24 hours
To assess the effect of SH-NPs on macrophage polarization, results showed that SH-NPs significantly reduced the expression of M2 macrophage marker CD206 and increased the expression of M1 macrophage marker CD86.
Pharmaceutics. 2024 Sep 17;16(9):1216.
DC2.4 cells
10.0 µM
24 hours
To evaluate the cellular uptake and STING pathway activation of SH-NPs, results showed that SH-NPs significantly increased the expression levels of p-TBK1 and p-IRF3 and enhanced IFN-β secretion.
Pharmaceutics. 2024 Sep 17;16(9):1216.
SR-717 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Lung ischemia/reperfusion injury model
Intraperitoneal injection
3 mg/kg
Single dose, 1 hour before surgery
Activation of STING aggravated endoplasmic reticulum stress (ERS), leading to increased apoptosis, inflammation, and oxidative stress, thereby exacerbating lung ischemia/reperfusion injury.
J Inflamm Res. 2022 Sep 5;15:5103-5119
Mice
Periodontitis mouse model
Intraperitoneal injection
30 mg/kg
Daily dosing for 7 days
SR-717-treated periodontitis mice displayed enhanced macrophage infiltration and M1 macrophage polarization in periodontal lesions compared with that in vehicle-treated periodontitis mice
Front Microbiol. 2023 Jun 19;14:1183415
BALB/c mice
RENCA renal tumor model
Intravenous injection
30.0 mg/kg
Single injection, observed for 16 days
To evaluate the tumor targeting and antitumor efficacy of SH-NPs, results showed that SH-NPs significantly enhanced drug accumulation in tumors and delayed tumor growth, with further improved therapeutic effects when combined with anti-PD-L1 antibody.
搜索
