{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:49:56Z","timestamp":1781563796594,"version":"3.54.5"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Department of Energy, Office of Biological and Environmental Research"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biomedical Technology Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cytotoxic accumulation of loosely bound mitochondrial Fe2+ is a hallmark of Friedreich's Ataxia (FA), a rare and fatal neuromuscular disorder with limited therapeutic options. There are no clinically approved medications targeting excess Fe2+ associated with FA or the neurological disorders Parkinson's disease and Multiple System Atrophy. Traditional iron-chelating drugs clinically approved for systemic iron overload that target ferritin-stored Fe3+ for urinary excretion demonstrated limited efficacy in FA and exacerbated ataxia. Poor treatment outcomes reflect inadequate binding to excess toxic Fe2+ or exceptionally high affinities (i.e. \u226410\u221231) for non-pathologic Fe3+ that disrupts intrinsic iron homeostasis. To understand previous treatment failures and identify beneficial factors for Fe2+-targeted therapeutics, we compared traditional Fe3+ chelators deferiprone (DFP) and deferasirox (DFX) with additional iron-binding compounds including ATH434, DMOG, and IOX3. ATH434 and DFX had moderate Fe2+ binding affinities (Kd\u2019s of 1\u20134 \u00a0\u00b5M), similar to endogenous iron chaperones, while the remaining had weaker divalent metal interactions. These compounds had low\/moderate affinities for Fe3+(0.46\u20139.59\u00a0\u00b5M) relative to DFX and DFP. While all compounds coordinated iron using molecular oxygen and\/or nitrogen ligands, thermodynamic analyses suggest ATH434 completes Fe2+ coordination using H2O. ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, mimicking natural endogenous iron binding proteins, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfae044","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T02:33:04Z","timestamp":1727231584000},"source":"Crossref","is-referenced-by-count":5,"title":["ATH434, a promising iron-targeting compound for treating iron regulation disorders"],"prefix":"10.1093","volume":"16","author":[{"given":"Ashley E","family":"Pall","sequence":"first","affiliation":[{"name":"De , Detroit, MI 48201 ,","place":["USA"]},{"name":"partment of Pharmaceutical Sciences, Wayne State University , Detroit, MI 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silas","family":"Bond","sequence":"additional","affiliation":[{"name":"Alterity Therapeutics Limited , Melbourne, 3000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle K","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Buffalo , Buffalo, NY 14203,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S","family":"Stoj","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chemistry and Physics, Niagara University , Lewiston, NY 14109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Deschamps","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chemistry and Physics, Niagara University , Lewiston, NY 14109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny","family":"Huggins","sequence":"additional","affiliation":[{"name":"Alterity Therapeutics Limited , Melbourne, 3000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Parsons","sequence":"additional","affiliation":[{"name":"Alterity Therapeutics Limited , Melbourne, 3000 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret J","family":"Bradbury","sequence":"additional","affiliation":[{"name":"Alterity Therapeutics Limited , Newark, CA 94560 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Kosman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Buffalo , Buffalo, NY 14203,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6298-088X","authenticated-orcid":false,"given":"Timothy L","family":"Stemmler","sequence":"additional","affiliation":[{"name":"De , Detroit, MI 48201 ,","place":["USA"]},{"name":"partment of Pharmaceutical Sciences, Wayne State University , Detroit, MI 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"issue":"1","key":"2025061011520361500_bib1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10408360701713104","article-title":"Oxidative stress and iron homeostasis: mechanistic and health aspects","volume":"45","author":"Galaris","year":"2008","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"issue":"7","key":"2025061011520361500_bib2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3390\/antiox9070597","article-title":"The role of oxidative stress in Parkinson's disease","volume":"9","author":"Chang","year":"2020","journal-title":"Antioxidants (Basel)"},{"issue":"1\u20132","key":"2025061011520361500_bib3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.jns.2005.03.012","article-title":"Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia","volume":"233","author":"Calabrese","year":"2005","journal-title":"J. Neurol. Sci."},{"issue":"1\u20132","key":"2025061011520361500_bib4","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S0005-2728(98)00115-7","article-title":"Mitochondrial dysfunction in neurodegenerative disorders","volume":"1366","author":"Schapira","year":"1998","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Bioenergetics"},{"issue":"3","key":"2025061011520361500_bib5","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1023\/B:NERE.0000014826.00881.c3","article-title":"Role of oxidative damage in Friedreich's ataxia","volume":"29","author":"Bradley","year":"2004","journal-title":"Neurochem. Res."},{"issue":"2","key":"2025061011520361500_bib6","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s40291-018-0373-5","article-title":"Oxidative stress in beta-thalassemia","volume":"23","author":"Fibach","year":"2019","journal-title":"Mol. Diagn. Ther."},{"issue":"4","key":"2025061011520361500_bib7","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1007\/s12265-016-9704-2","article-title":"Iron overload or oxidative stress? Insight into a mechanism of early cardiac manifestations of asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity","volume":"9","author":"Shizukuda","year":"2016","journal-title":"J. Cardiovasc. Trans. Res."},{"issue":"2","key":"2025061011520361500_bib8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1267\/ahc.10005","article-title":"Involvement of 4-hydroxy-2-nonenal accumulation in multiple system atrophy","volume":"43","author":"Shibata","year":"2010","journal-title":"Acta. Histochem. Cytochem."},{"issue":"24","key":"2025061011520361500_bib9","doi-asserted-by":"publisher","first-page":"17791","DOI":"10.1074\/jbc.M113.460253","article-title":"Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin","volume":"288","author":"Leidgens","year":"2013","journal-title":"J. Biol. Chem."},{"issue":"11","key":"2025061011520361500_bib10","doi-asserted-by":"publisher","first-page":"2835","DOI":"10.1093\/emboj\/20.11.2835","article-title":"Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1","volume":"20","author":"Ogawa","year":"2001","journal-title":"EMBO J."},{"issue":"22","key":"2025061011520361500_bib11","doi-asserted-by":"publisher","first-page":"8031","DOI":"10.1073\/pnas.1402732111","article-title":"Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase","volume":"111","author":"Frey","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"issue":"11","key":"2025061011520361500_bib12","doi-asserted-by":"publisher","first-page":"6006","DOI":"10.3390\/ijms22116006","article-title":"Molecular details of the Frataxin-Scaffold interaction during mitochondrial Fe-S cluster assembly","volume":"22","author":"Campbell","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"8","key":"2025061011520361500_bib13","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/S0968-0004(00)01589-9","article-title":"Maturation of cellular Fe-S proteins: an essential function of mitochondria","volume":"25","author":"Lill","year":"2000","journal-title":"Trends Biochem. Sci"},{"key":"2025061011520361500_bib14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0070-2137(97)80001-5","article-title":"Regulation of iron metabolism in eukaryotes","volume":"35","author":"Rouault","year":"1997","journal-title":"Curr. Top. Cell. Regul."},{"key":"2025061011520361500_bib15","doi-asserted-by":"publisher","first-page":"103181","DOI":"10.1016\/j.micron.2021.103181","article-title":"Molecular characteristics of proteins within the mitochondrial Fe-S cluster assembly complex","volume":"153","author":"Hinton","year":"2022","journal-title":"Micron"},{"issue":"4","key":"2025061011520361500_bib16","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1182\/blood.V97.4.1115","article-title":"ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture","volume":"97","author":"Hershko","year":"2001","journal-title":"Blood"},{"key":"2025061011520361500_bib17","volume-title":"Drugs@FDA (016267 Deferoxamine Mesylate)","year":"2022"},{"key":"2025061011520361500_bib18","volume-title":"Deferoxamine","author":"Velasquez","year":"2024"},{"issue":"1","key":"2025061011520361500_bib19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1021\/acschembio.7b00851","article-title":"Advances in the Chemical Biology of Desferrioxamine B","volume":"13","author":"Codd","year":"2018","journal-title":"ACS Chem. Biol."},{"issue":"1","key":"2025061011520361500_bib20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3390\/jof8010021","article-title":"Biosynthesis pathways, transport mechanisms and biotechnological applications of fungal siderophores","volume":"8","author":"Pecoraro","year":"2021","journal-title":"J Fungi (Basel)"},{"issue":"45","key":"2025061011520361500_bib21","doi-asserted-by":"publisher","first-page":"26723","DOI":"10.1074\/jbc.270.45.26723","article-title":"Siderophores: structure and function of microbial iron transport compounds","volume":"270","author":"Neilands","year":"1995","journal-title":"J. Biol. Chem."},{"issue":"18","key":"2025061011520361500_bib22","doi-asserted-by":"crossref","first-page":"5766","DOI":"10.1021\/ja00538a012","article-title":"Circular dichroism, crystal structure, and absolute configuration of the siderophore ferric N,N',N\"-triacetylfusarinine, FeC39H57N6O15","volume":"102","author":"Hossain DLE-W","year":"1980","journal-title":"J. Am. Chem. Soc."},{"issue":"3","key":"2025061011520361500_bib23","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1128\/MMBR.00012-07","article-title":"Siderophore-based iron acquisition and pathogen control","volume":"71","author":"Miethke","year":"2007","journal-title":"Microbiol. Mol. Biol. Rev."},{"issue":"3641","key":"2025061011520361500_bib24","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1126\/science.146.3641.261","article-title":"Crystal and molecular structure of Ferrichrome A","volume":"146","author":"Zalkin","year":"1964","journal-title":"Science"},{"issue":"3","key":"2025061011520361500_bib25","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1021\/acs.bioconjchem.8b00924","article-title":"Cell permeable imidazole-desferrioxamine conjugates: synthesis and in vitro evaluation","volume":"30","author":"Pramanik","year":"2019","journal-title":"Bioconjugate Chem."},{"issue":"4968","key":"2025061011520361500_bib26","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/205281b0","article-title":"Chelation of ferrous sulphate solutions by desferrioxamine B","volume":"205","author":"Goodwin","year":"1965","journal-title":"Nature"},{"issue":"4","key":"2025061011520361500_bib27","first-page":"239","article-title":"A review on iron chelators in treatment of iron overload syndromes","volume":"10","author":"Mobarra","year":"2016","journal-title":"Int. J. Hematol. Oncol. Stem Cell Res."},{"issue":"4","key":"2025061011520361500_bib28","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1093\/clinchem\/38.4.562","article-title":"Complexation of iron with the orally active decorporation drug L1 (3-hydroxy-1,2-dimethyl-4-pyridinone)","volume":"38","author":"Kline","year":"1992","journal-title":"Clin. Chem."},{"issue":"2","key":"2025061011520361500_bib29","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0020-1693(00)86121-6","article-title":"Crystal structure of the tris 1,2-dimethyl-3-hydroxy-4-pyridinone (DMHP) complex with the Fe(III) ion","volume":"196","author":"Clarke Eric","year":"1992","journal-title":"Inorg. Chim. Acta"},{"issue":"21","key":"2025061011520361500_bib30","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1002\/ejic.200400363","article-title":"Complex formation of ICL670 and related ligands with Fe&lt;SUP&gt;III&lt;\/SUP&gt;and Fe&lt;SUP&gt;II&lt;\/SUP&gt;","volume":"2004","author":"Steinhauser","year":"2004","journal-title":"Eur. J. Inorg. Chem."},{"issue":"4\u20135","key":"2025061011520361500_bib31","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s10534-020-00243-3","article-title":"Iron chelators in cancer therapy","volume":"33","author":"Ibrahim","year":"2020","journal-title":"Biometals"},{"issue":"2","key":"2025061011520361500_bib32","doi-asserted-by":"publisher","first-page":"e14607","DOI":"10.1111\/cns.14607","article-title":"Efficacy of the iron-chelating agent, deferiprone, in patients with Parkinson's disease: a systematic review and meta-analysis","volume":"30","author":"Negida","year":"2024","journal-title":"CNS Neurosci. Ther."},{"issue":"6","key":"2025061011520361500_bib33","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/j.jhep.2010.04.039","article-title":"Hepatic but not brain iron is rapidly chelated by deferasirox in aceruloplasminemia due to a novel gene mutation","volume":"53","author":"Finkenstedt","year":"2010","journal-title":"J. Hepatol."},{"issue":"2","key":"2025061011520361500_bib34","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s004010050966","article-title":"Markedly different course of Friedreich's ataxia in sib pairs with similar GAA repeat expansions in the frataxin gene","volume":"97","author":"Klopstock","year":"1999","journal-title":"Acta Neuropathol."},{"issue":"1","key":"2025061011520361500_bib35","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1532-429X-13-34","article-title":"Effect of deferiprone or deferoxamine on right ventricular function in thalassemia major patients with myocardial iron overload","volume":"13","author":"Smith","year":"2011","journal-title":"J. Cardiovasc. Magn. Reson."},{"issue":"1","key":"2025061011520361500_bib36","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00415-019-09577-6","article-title":"Werring DJ. Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis","volume":"267","author":"Sammaraiee","year":"2020","journal-title":"J. Neurol."},{"issue":"4","key":"2025061011520361500_bib37","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1517\/14740338.2010.497138","article-title":"Introduction of higher doses of deferasirox: better efficacy but not effective iron removal from the heart and increased risks of serious toxicities","volume":"9","author":"Kontoghiorghes","year":"2010","journal-title":"Expert Opin. Drug Saf."},{"issue":"11","key":"2025061011520361500_bib38","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1093\/hmg\/6.11.1771","article-title":"Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes","volume":"6","author":"Campuzano","year":"1997","journal-title":"Hum. Mol. Genet."},{"issue":"5254","key":"2025061011520361500_bib39","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science"},{"issue":"25","key":"2025061011520361500_bib40","doi-asserted-by":"publisher","first-page":"7767","DOI":"10.1021\/bi060424r","article-title":"Monomeric yeast Frataxin is an iron-binding protein","volume":"45","author":"Cook","year":"2006","journal-title":"Biochemistry"},{"issue":"26","key":"2025061011520361500_bib41","doi-asserted-by":"publisher","first-page":"6917","DOI":"10.1021\/bi800366d","article-title":"Drosophila Frataxin: an iron chaperone during cellular Fe\u2212S cluster bioassembly","volume":"47","author":"Kondapalli","year":"2008","journal-title":"Biochemistry"},{"issue":"35","key":"2025061011520361500_bib42","doi-asserted-by":"publisher","first-page":"26737","DOI":"10.1074\/jbc.R110.118679","article-title":"Frataxin and mitochondrial FeS cluster biogenesis","volume":"285","author":"Stemmler","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2025061011520361500_bib43","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jinorgbio.2018.03.007","article-title":"Interactions of iron-bound frataxin with ISCU and ferredoxin on the cysteine desulfurase complex leading to Fe-S cluster assembly","volume":"183","author":"Cai","year":"2018","journal-title":"J. Inorg. Biochem."},{"issue":"5","key":"2025061011520361500_bib44","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/S0887-8994(03)00004-3","article-title":"Friedreich's ataxia","volume":"28","author":"Alper","year":"2003","journal-title":"Pediatr. Neurol."},{"issue":"20","key":"2025061011520361500_bib45","doi-asserted-by":"publisher","first-page":"19794","DOI":"10.1074\/jbc.M500397200","article-title":"Frataxin and mitochondrial carrier proteins, Mrs3p and Mrs4p, cooperate in providing iron for heme synthesis","volume":"280","author":"Zhang","year":"2005","journal-title":"J. Biol. Chem."},{"issue":"4","key":"2025061011520361500_bib46","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1002\/ana.24248","article-title":"Deferiprone in Friedreich ataxia: a 6-month randomized controlled trial","volume":"76","author":"Pandolfo","year":"2014","journal-title":"Ann. Neurol."},{"issue":"43","key":"2025061011520361500_bib47","doi-asserted-by":"crossref","first-page":"29126","DOI":"10.1074\/jbc.M803028200","article-title":"The redox environment in the mitochondrial intermembrane space is maintained seperately from the cytosol and matrix","volume":"283","author":"Hu","year":"2008","journal-title":"J. Biol. Chem."},{"issue":"27","key":"2025061011520361500_bib48","doi-asserted-by":"publisher","first-page":"25305","DOI":"10.1074\/jbc.M500095200","article-title":"Glutathione redox state regulates mitochondrial reactive oxygen production","volume":"280","author":"Shen","year":"2005","journal-title":"J. Biol. Chem."},{"issue":"1","key":"2025061011520361500_bib49","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.tips.2020.11.003","article-title":"Ferrous Iron-Dependent Pharmacology","volume":"42","author":"Gonciarz","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"2025061011520361500_bib50","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.bbrc.2021.02.113","article-title":"Cultivation of human skin cells under physiological oxygen concentration modulates expression of skin significant genes and response to hydroxy acids","volume":"551","author":"Lee","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"3","key":"2025061011520361500_bib51","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1179\/135100009X392566","article-title":"Hydroxyl radical is produced via the Fenton reaction in submitochondrial particles under oxidative stress: implications for diseases associated with iron accumulation","volume":"14","author":"Thomas","year":"2009","journal-title":"Redox Report"},{"key":"2025061011520361500_bib52","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/j.chemosphere.2017.05.039","article-title":"Hydroxyl radical yields in the Fenton process under various pH, ligand concentrations and hydrogen peroxide\/Fe(II) ratios","volume":"182","author":"Fischbacher","year":"2017","journal-title":"Chemosphere"},{"issue":"2","key":"2025061011520361500_bib53","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3109\/10715769109094123","article-title":"The autoxidation of iron(II) in aqueous systems: the effects of iron chelation by physiological, non-physiological and therapeutic chelators on the generation of reactive oxygen species and the inducement of biomolecular damage","volume":"14","author":"Burkitt","year":"1991","journal-title":"Free Radic. Res. Commun."},{"issue":"1","key":"2025061011520361500_bib54","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/0304-4165(73)90019-6","article-title":"Facilitation of Fe(II) autoxidation by Fe(3) complexing agents","volume":"329","author":"Harris","year":"1973","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014General Subjects"},{"issue":"1","key":"2025061011520361500_bib55","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.ccr.2012.06.030","article-title":"Iron metabolism in aerobes: managing ferric iron hydrolysis and ferrous iron autoxidation","volume":"257","author":"Kosman","year":"2013","journal-title":"Coord. Chem. Rev."},{"issue":"9","key":"2025061011520361500_bib56","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1021\/ic00334a023","article-title":"Kinetics and mechanism of the autoxidation of iron(II) induced through chelation by ethylenediaminetetraacetate and related ligand","volume":"29","author":"Zang","year":"1990","journal-title":"Inorg. Chem."},{"issue":"2","key":"2025061011520361500_bib57","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1006\/abbi.2001.2694","article-title":"Iron autoxidation and free radical generation: effects of buffers, ligands, and chelators","volume":"397","author":"Welch","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"issue":"3","key":"2025061011520361500_bib58","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/S0304-4165(02)00218-0","article-title":"Mechanisms underlying the cytotoxic effects of Tachpyr\u2014a novel metal chelator","volume":"1571","author":"Samuni","year":"2002","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014General Subjects"},{"issue":"30","key":"2025061011520361500_bib59","doi-asserted-by":"publisher","first-page":"3232","DOI":"10.1039\/b704102k","article-title":"Hydrazone chelators for the treatment of iron overload disorders: iron coordination chemistry and biological activity","author":"Bernhardt","year":"2007","journal-title":"Dalton Trans."},{"issue":"26","key":"2025061011520361500_bib60","doi-asserted-by":"publisher","first-page":"5436","DOI":"10.1021\/bi100558z","article-title":"Biophysical characterization of iron in mitochondria isolated from respiring and fermenting yeast","volume":"49","author":"Garber Morales","year":"2010","journal-title":"Biochemistry"},{"issue":"22","key":"2025061011520361500_bib61","doi-asserted-by":"publisher","first-page":"3442","DOI":"10.1021\/bi5015437","article-title":"Detection of labile low-molecular-mass transition metal complexes in mitochondria","volume":"54","author":"McCormick","year":"2015","journal-title":"Biochemistry"},{"issue":"4","key":"2025061011520361500_bib62","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1021\/jacs.2c06625","article-title":"Labile iron pool of isolated Escherichia coli cytosol likely includes Fe-ATP and Fe-Citrate but not Fe-Glutathione or Aqueous Fe","volume":"145","author":"Brawley","year":"2023","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2025061011520361500_bib63","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1146\/annurev.biochem.77.061606.161055","article-title":"Cellular defenses against superoxide and hydrogen peroxide","volume":"77","author":"Imlay","year":"2008","journal-title":"Annu. Rev. Biochem."},{"issue":"6","key":"2025061011520361500_bib64","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1128\/JB.185.6.1942-1950.2003","article-title":"High levels of intracellular cysteine promote oxidative DNA damage by driving the fenton reaction","volume":"185","author":"Park","year":"2003","journal-title":"J. Bacteriol."},{"issue":"3","key":"2025061011520361500_bib65","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1093\/hmg\/ddi461","article-title":"Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity","volume":"15","author":"Gakh","year":"2006","journal-title":"Hum. Mol. Genet."},{"issue":"11","key":"2025061011520361500_bib66","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1039\/C9MT00172G","article-title":"Unique roles of iron and zinc binding to the yeast Fe-S cluster scaffold assembly protein \u201cIsu1\u201d ,","volume":"11","author":"Lewis","year":"2019","journal-title":"Metallomics"},{"issue":"1","key":"2025061011520361500_bib67","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1039\/C6MT00163G","article-title":"In vitro characterization of a novel Isu homologue from Drosophila melanogaster for de novo FeS-cluster formation","volume":"9","author":"Dzul","year":"2017","journal-title":"Metallomics"},{"issue":"7","key":"2025061011520361500_bib68","doi-asserted-by":"publisher","first-page":"e0254794","DOI":"10.1371\/journal.pone.0254794","article-title":"The iron chelator, PBT434, modulates transcellular iron trafficking in brain microvascular endothelial cells","volume":"16","author":"Bailey","year":"2021","journal-title":"PLoS One"},{"issue":"6","key":"2025061011520361500_bib69","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1007\/s13311-022-01300-0","article-title":"ATH434 rescues pre-motor hyposmia in a mouse model of parkinsonism","volume":"19","author":"Beauchamp","year":"2022","journal-title":"Neurotherapeutics"},{"issue":"4","key":"2025061011520361500_bib70","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.3233\/JPD-212731","article-title":"ATH434 reverses colorectal dysfunction in the A53T mouse model of Parkinson's disease","volume":"11","author":"Diwakarla","year":"2021","journal-title":"JPD"},{"issue":"1","key":"2025061011520361500_bib71","doi-asserted-by":"publisher","first-page":"105","DOI":"10.3233\/JPD-212877","article-title":"The compound ATH434 prevents Alpha-Synuclein toxicity in a murine model of multiple system atrophy","volume":"12","author":"Finkelstein","year":"2022","journal-title":"JPD"},{"issue":"11","key":"2025061011520361500_bib72","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1002\/mds.28714","article-title":"ATH434 reduces alpha-Synuclein-related neurodegeneration in a murine model of multiple system atrophy","volume":"36","author":"Heras-Garvin","year":"2021","journal-title":"Mov. Disord."},{"issue":"1","key":"2025061011520361500_bib73","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s40478-017-0456-2","article-title":"The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease","volume":"5","author":"Finkelstein","year":"2017","journal-title":"Acta. Neuropathol. Commun."},{"key":"2025061011520361500_bib74","article-title":"Study of ATH434 in participants with multiple system atrophy","author":"Therapeutics","year":"2024"},{"issue":"2","key":"2025061011520361500_bib75","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1124\/jpet.119.262782","article-title":"DMOG, a prolyl hydroxylase inhibitor, increases hemoglobin levels without exacerbating hypertension and renal injury in salt-sensitive hypertensive rats","volume":"372","author":"Kato","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"7","key":"2025061011520361500_bib76","doi-asserted-by":"publisher","first-page":"e0132004","DOI":"10.1371\/journal.pone.0132004","article-title":"Potent and selective triazole-based inhibitors of the hypoxia-inducible factor prolyl-hydroxylases with activity in the murine brain","volume":"10","author":"Chan","year":"2015","journal-title":"PLoS One"},{"key":"2025061011520361500_bib77","doi-asserted-by":"publisher","first-page":"110882","DOI":"10.1016\/j.jinorgbio.2019.110882","article-title":"Refinement of protein Fe(II) binding characteristics utilizing a competition assay exploiting small molecule ferrous chelators","volume":"203","author":"Koebke","year":"2020","journal-title":"J. Inorg. Biochem."},{"issue":"15","key":"2025061011520361500_bib78","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.1021\/ja9642121","article-title":"Fluorescent chemosensors for divalent zinc based on zinc finger domains","volume":"119","author":"Walkup","year":"1997","journal-title":"J. Am. Chem. Soc."},{"issue":"13","key":"2025061011520361500_bib79","doi-asserted-by":"publisher","first-page":"e106742","DOI":"10.15252\/embj.2020106742","article-title":"The DnaJ proteins DJA6 and DJA5 are essential for chloroplast iron-sulfur cluster biogenesis","volume":"40","author":"Zhang","year":"2021","journal-title":"EMBO J."},{"issue":"2","key":"2025061011520361500_bib80","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1107\/S0909049500016423","article-title":"Progress and challenges in the theory and interpretation of X-ray spectra","volume":"8","author":"Rehr","year":"2001","journal-title":"J. Synchrotron Rad."},{"key":"2025061011520361500_bib81","volume-title":"EXAFSPAK","author":"George","year":"2001"},{"issue":"4","key":"2025061011520361500_bib82","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/j.jinorgbio.2007.10.012","article-title":"Potentiometric, spectrophotometric and calorimetric study on iron(III) and copper(II) complexes with 1,2-dimethyl-3-hydroxy-4-pyridinone","volume":"102","author":"Nurchi","year":"2008","journal-title":"J. Inorg. Biochem."},{"issue":"3","key":"2025061011520361500_bib83","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1107\/S0108768102003890","article-title":"The cambridge structural database: a quarter of a million crystal structures and rising","volume":"58","author":"Allen","year":"2002","journal-title":"Acta. Crystallogr. B. Struct. Sci."},{"issue":"6","key":"2025061011520361500_bib84","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1007\/s11426-019-9464-1","article-title":"Tracking the multiple-step formation of an iron(III) complex and its application in photodynamic therapy for breast cancer","volume":"62","author":"Zhu","year":"2019","journal-title":"Sci. China Chem."},{"issue":"47","key":"2025061011520361500_bib85","doi-asserted-by":"publisher","first-page":"16455","DOI":"10.1039\/C7DT02666H","article-title":"Cobalt, nickel, and iron complexes of 8-hydroxyquinoline-di(2-picolyl)amine for light-driven hydrogen evolution","volume":"46","author":"Carmo dos Santos","year":"2017","journal-title":"Dalton Trans."}],"container-title":["Metallomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/metallomics\/advance-article-pdf\/doi\/10.1093\/mtomcs\/mfae044\/59318296\/mfae044.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/metallomics\/article-pdf\/16\/10\/mfae044\/59718425\/mfae044.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/metallomics\/article-pdf\/16\/10\/mfae044\/59718425\/mfae044.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T15:52:11Z","timestamp":1749570731000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/metallomics\/article\/doi\/10.1093\/mtomcs\/mfae044\/7774404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,24]]},"references-count":85,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10,4]]}},"URL":"https:\/\/doi.org\/10.1093\/mtomcs\/mfae044","relation":{},"ISSN":["1756-591X"],"issn-type":[{"value":"1756-591X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,10]]},"published":{"date-parts":[[2024,9,24]]},"article-number":"mfae044"}}