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Updated: Aug 19, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Structure-activity relationship study of amidobenzimidazole derivatives as stimulator of interferon genes (STING)
Xue Liu1, Mingjin Wang1, Minjian Yang1
1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, China.
Abstract:
Stimulator of interferon genes (STING) is a crucial adaptor protein that can regulate the innate immune response by inducing the secretion of type Ι interferons and other cytokines after recognizing endogenous or exogenous DNA. Due to the key role of STING in the innate immune system, the activation of STING pathway is expected to be an efficacious immunotherapeutic tactic to treat cancer. In this study, we performed a structure-activity relationship study of amidobenzimidazole monomer, led to a series of ABZI STING agonist derivatives with potent STING-activating effects. Among them, compound 72, as a representative compound, markedly activated the STING-TBK1-IRF3 signaling pathway and significantly increased the mRNA and protein levels of IFN-β, CXCL10 and IL-6 in both WT THP-1 cells and human peripheral blood mononuclear cells (hPBMCs). In addition, it was confirmed that compound 72 was highly selective for human STING, specifically targeting human STING signaling and showing no activation of m-STING.
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