SR-717 is a small-molecule non-nucleoside activator of STING. It is thought that having STING activated may help to prevent IR-induced damage of healthy cells during cancer radiotherapy. IR damage is a common complication of radiotherapy.
Recently, a research project using a mouse model attempted to confirm SR-717 as a STING activator. To begin, the mice were treated via peritoneal injection at 18 hours and 2 hours prior to IR treatment. A second group was treated with both SR-717 and C176, which is a known STING inhibitor. The mice were then treated with total body irradiation.
Next, the intestines of the mice were assayed 3.5 days after irradiation. The intestinal damage was found to be significantly reduced in the SR-717 treated mice. Further analysis suggested that SR-717 lead to regeneration of intestinal organoids and activated the immune system too.
These results do indicate this molecule upregulates not only expression of STING, but also TLR2, and thereby activates immunity. TLR2 is a component of the innate immune system. Further research should be done to confirm and expand on these findings.
Fang D, Duan W, Zhai X, et al. SR-717, a non-nucleoside STING agonist, displayed anti-radiation activity in a IL-6 dependent manner. FASEB J. 2025 Jun 15;39(11):e70644. PMID: 40448435