Jeon, Min Jae LEE HYE LIM Lee Jee Hee Baek Soo Yeon Lee Donghee Jo, Seongman Lee, Joo-Youn KANG MI SO JUNG HEERA Han, Soo Bong Kim, Nam-Jung Lee, Sanghee Kim, Hyejin 2024-01-12T03:31:39Z 2024-01-12T03:31:39Z 2022-04-21 2022-04 0022-2623 https://pubs.kist.re.kr/handle/201004/76753 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 English American Chemical Society Development of Potent Immune Modulators Targeting Stimulator of Interferon Genes Receptor Article 10.1021/acs.jmedchem.1c01795 1 Journal of Medicinal Chemistry, v.65, no.7, pp.5407 - 5432 Journal of Medicinal Chemistry 65 7 5407 5432 N scie scopus 000792282200013 Chemistry, Medicinal Pharmacology & Pharmacy Article CYCLIC GMP-AMP CHECKPOINT BLOCKADE CANCER-IMMUNOTHERAPY ANTITUMOR-ACTIVITY STING ACTIVATION DISCOVERY MOUSE EXPRESSION INHIBITORS THERAPY