Development of Potent Immune Modulators Targeting Stimulator of Interferon Genes Receptor

Stimulator of interferon genes (STING) is an endoplasmic reticulum-membrane protein that plays importantroles in cancer immunotherapy by activating innate immuneresponses. We designed and synthesized STING modulators andcharacterized compounds4aand4cthat share a crucialamidobenzimidazole moiety.In vitroSTING binding and cell-based activity assays demonstrated the potency and efficacy of thecompounds that function as direct STING agonists by stimulatingSTING downstream signaling and promoting type I interferonimmune responses.In vitrometabolic studies and the pharmaco-kinetic properties of the compounds led us to investigate theiranticancer activity in anin vivosyngeneic model.Intravenousinjection of compounds4aand4csignificantly decreased tumorvolume in a CT26 murine colorectal carcinoma model, and the immunological memory-derived cancer inhibition was observed in4c-treated mouse models. The present results suggest the therapeutic potential of the compounds for cancer immunotherapy via STING-mediated immune activation

Automated summary

Stimulator of interferon genes (STING) is an endoplasmic reticulum membrane protein that plays important roles in cancer immunotherapy. Researchers have synthesized and characterized STING modulators that stimulate downstream signaling and promote immune responses, suggesting their therapeutic potential for cancer treatment.