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Numerous studies reveal that ferroptosis participates in multiple types of tissue injury including ischaemia\u2013reperfusion (I\/R) injury and doxorubicin (Dox)\u2010induced damage. Targeting ferroptosis is a promising approach for disease treatment as the blockade of ferroptosis efficiently alleviates the symptoms. However, no known ferroptosis inhibitors have been used for clinical treatment. Although certain clinical compounds act as ferroptosis inhibitors in vitro, whether these drugs cure tissue injury by suppressing ferroptosis is little known. Here, by screening a large panel of drugs used in the clinic, it is identified that dipyridamole significantly attenuates Dox or I\/R\u2010induced cardiac injury. Moreover, dipyridamole can achieve a good therapeutic effect on \u00a0liver and kidney injury. Mechanistically, dipyridamole\u2010mediated ferroptosis inhibition is strictly dependent on solute carrier family 7 member 11 (SLC7A11). Dipyridamole down\u2010regulates the expression of ring finger protein 126 (RNF126), which is an E3 ligase to ubiquitinate SLC7A11 for proteasome degradation. Deficiency of SLC7A11 largely blocks the protective role of dipyridamole in vitro and in vivo. Together, the findings uncover that dipyridamole acts as a clinical compound to alleviate organ injury via suppressing ferroptosis, providing novel insights into the clinical therapy for ferroptosis\u2010related tissue damage.<\/jats:p>","DOI":"10.1002\/advs.202500566","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T05:46:08Z","timestamp":1747201568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dipyridamole Acts as Clinical Ferroptosis Inhibitor to Prevent from Tissue Injury"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiao","family":"Zhuang","sequence":"first","affiliation":[{"name":"Department of Cell Biology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University  Jinan 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of 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