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No physiological mechanism is available to excrete excess iron and iron overload to promote lipid peroxidation to induce\u00a0ferroptosis, thus iron chelation becomes critical for preventing ion toxicity in these patients. To date, several iron chelators have been approved for iron chelation therapy, such as deferiprone and deferoxamine, but the current iron chelators suffer from significant limitations. In this context, new agents are continuously sought. Here, a library of new deferric amine compounds (\n                    <jats:bold>DFAs<\/jats:bold>\n                    ) with adjustable skeleton and flexibility is synthesized by adopting the beneficial properties of conventional chelators. After careful evaluations, compound\n                    <jats:bold>DFA1<\/jats:bold>\n                    is found to have greater efficacy in binding iron through two molecular oxygens in the phenolic hydroxyl group and the nitrogen atom in the amine with a 2:1 stoichiometry. This compound remarkably ameliorates iron overload in diverse murine models through both oral and intravenous administration, including hemochromatosis, high iron diet\u2010induced, and iron dextran\u2010stimulated iron accumulation. Strikingly, this compound is found to suppress iron\u2010induced ferroptosis by modulating the intracellular signaling that drives lipid peroxidation. This study opens a new approach for the development of iron chelators to treat iron overload.\n                  <\/jats:p>","DOI":"10.1002\/advs.202202679","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T21:42:17Z","timestamp":1661722937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["New Deferric Amine Compounds Efficiently Chelate Excess Iron to Treat Iron Overload Disorders and to Prevent Ferroptosis"],"prefix":"10.1002","volume":"9","author":[{"given":"Wenya","family":"Feng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing 100085 P. R. China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Ganz","sequence":"additional","affiliation":[{"name":"Department of Medicine David Geffen School of Medicine University of California  Los Angeles CA 90095 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Fudan University  2005 Songhu Road Shanghai 200438 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-0734","authenticated-orcid":false,"given":"Sijin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing 100085 P. R. China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 P. R. 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