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STING, a pattern recognition receptor located on the endoplasmic reticulum membrane of immune cells, binds with endogenous cyclic dinucleotides. STING undergoes phosphorylation, triggering the STING\u2010TBK1\u2010IRF3 pathway and NF\u2010\u03baB pathway, resulting in the release of IFN\u2010\u03b2 and other pro\u2010inflammatory cytokines, ultimately enhancing the activation of tumor\u2010specific T cells. This mechanism serves to complement the limitations of immune checkpoint inhibitors and enhances the efficiency of the immune response. This study selected benzimidazole <jats:bold>compounds GSK<\/jats:bold> and <jats:bold>SR\u2010717<\/jats:bold>, which exhibit promising potential as patented medicines, as our lead compounds. Aiming to address the challenges associated with the short half\u2010life of benzimidazole compounds and the limited molecular activity of <jats:bold>SR\u2010717<\/jats:bold>, we designed and synthesized a series of STING agonists (<jats:bold>compounds 6~29<\/jats:bold>). The <jats:bold>compound 17<\/jats:bold> showed excellent agonistic activity on hSTING protein <jats:italic>in\u2005vitro<\/jats:italic>. The cytotoxicity tests of all the synthesized compounds were performed <jats:italic>in\u2005vitro<\/jats:italic>. Performed <jats:italic>in\u2005vivo<\/jats:italic> pharmacokinetic studies on the most promising compounds and conducted molecular docking analyses.<\/jats:p>","DOI":"10.1002\/cmdc.202400695","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T11:24:50Z","timestamp":1734953090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design, Synthesis, and Biological Assessment of Novel Aminobenzidazole Agonists Targeting the Stimulator of Interferon Genes (STING) Receptor Signaling Pathway for Oncology Immunotherapy"],"prefix":"10.1002","volume":"20","author":[{"given":"Yiqing","family":"Fan","sequence":"first","affiliation":[{"name":"Center of Drug Discovery State Key Laboratory of Natural Medicines China Pharmaceutical University  24 Tongjiaxiang Nanjing 210009 PR 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Key Laboratory of Natural Medicines China Pharmaceutical University  24 Tongjiaxiang Nanjing 210009 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Drug Discovery State Key Laboratory of Natural Medicines China Pharmaceutical University  24 Tongjiaxiang Nanjing 210009 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-0992","authenticated-orcid":false,"given":"Hai","family":"Qian","sequence":"additional","affiliation":[{"name":"Center of Drug Discovery State Key Laboratory of Natural Medicines China Pharmaceutical University  24 Tongjiaxiang Nanjing 210009 PR China"},{"name":"Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease China Pharmaceutical University  24 Tongjiaxiang Nanjing 210009 PR 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