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It is essential to identify specifically effective lead compounds to inhibit the signaling. Herein, it is shown that carnosic acid (CA), an active ingredient of medicinal plant\n                    <jats:italic>Rosmarinus officinalis L<\/jats:italic>\n                    ., specifically suppressed cGAS\u2010STING pathway activation and the subsequent inflammatory responses. Mechanistically, CA directly bound to STING C\u2010terminal tail (CTT), impeded the recruitment of TANK\u2010binding kinase 1 (TBK1) onto STING signalosome, thereby blocking the phosphorylation of STING and interferon regulatory factor 3 (IRF3) nuclear translocation. Importantly, CA dramatically attenuated STING\u2010mediated inflammatory responses in vivo. Consistently, CA has a salient ameliorative effect on autoinflammatory disease model mediated by\n                    <jats:italic>Trex1<\/jats:italic>\n                    deficiency, via inhibition of the cGAS\u2010STING signaling. Notably, the study further indicates that phenolic hydroxyl groups are essential for CA\u2010mediated STING inhibitory activity. Collectively, the results thus identify STING as one of the crucial targets of CA for mediating CA's anti\u2010inflammatory activity, and further reveal that STING CTT may be a novel promising target for drug development.\n                  <\/jats:p>","DOI":"10.1002\/advs.202417686","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T14:50:36Z","timestamp":1739890236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Carnosic Acid Directly Targets STING C\u2010Terminal Tail to Improve STING\u2010Mediated Inflammatory Diseases"],"prefix":"10.1002","volume":"12","author":[{"given":"Wenqing","family":"Mu","sequence":"first","affiliation":[{"name":"Department of Hepatology the Fifth Medical Center of PLA General Hospital  Beijing 100039 China"},{"name":"School of Traditional Chinese Medicine Capital Medical University  Beijing 100069 China"},{"name":"State Key Laboratory of 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