{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:31:38Z","timestamp":1768487498709,"version":"3.49.0"},"reference-count":263,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,4]],"date-time":"2023-03-04T00:00:00Z","timestamp":1677888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The historical insights and background of the discovery, development and clinical use of deferiprone (L1) and the maltol\u2013iron complex, which were discovered over 40 years ago, highlight the difficulties, complexities and efforts in general orphan drug development programs originating from academic centers. Deferiprone is widely used for the removal of excess iron in the treatment of iron overload diseases, but also in many other diseases associated with iron toxicity, as well as the modulation of iron metabolism pathways. The maltol\u2013iron complex is a recently approved drug used for increasing iron intake in the treatment of iron deficiency anemia, a condition affecting one-third to one-quarter of the world\u2019s population. Detailed insights into different aspects of drug development associated with L1 and the maltol\u2013iron complex are revealed, including theoretical concepts of invention; drug discovery; new chemical synthesis; in vitro, in vivo and clinical screening; toxicology; pharmacology; and the optimization of dose protocols. The prospects of the application of these two drugs in many other diseases are discussed under the light of competing drugs from other academic and commercial centers and also different regulatory authorities. The underlying scientific and other strategies, as well as the many limitations in the present global scene of pharmaceuticals, are also highlighted, with an emphasis on the priorities for orphan drug and emergency medicine development, including the roles of the academic scientific community, pharmaceutical companies and patient organizations.<\/jats:p>","DOI":"10.3390\/ijms24054970","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T03:49:08Z","timestamp":1678074548000},"page":"4970","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Deferiprone and Iron\u2013Maltol: Forty Years since Their Discovery and Insights into Their Drug Design, Development, Clinical Use and Future Prospects"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3364-7340","authenticated-orcid":false,"given":"George J.","family":"Kontoghiorghes","sequence":"first","affiliation":[{"name":"Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol 3021, Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100866","DOI":"10.1016\/j.mam.2020.100866","article-title":"Basics and principles of cellular and systemic iron homeostasis","volume":"75","author":"Katsarou","year":"2020","journal-title":"Mol. Asp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gozzelino, R., and Arosio, P. (2016). Iron Homeostasis in Health and Disease. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010130"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF02829934","article-title":"A precious metal: Iron, an essential nutrient for all cells","volume":"1","author":"Cairo","year":"2006","journal-title":"Genes Nutr."},{"key":"ref_4","first-page":"93","article-title":"Zinc: An overview","volume":"11","author":"Prasad","year":"1995","journal-title":"Nutrition"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1146\/annurev.bi.61.070192.004341","article-title":"Zinc proteins: Enzymes, storage proteins, transcription factors, and replication proteins","volume":"61","author":"Coleman","year":"1992","journal-title":"Annu. Rev. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1136\/bmj.326.7386.409","article-title":"Zinc deficiency","volume":"326","author":"Prasad","year":"2003","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.2741\/1424","article-title":"Copper storage diseases: Menkes, Wilson\u2019s, and Cancer","volume":"9","author":"Daniel","year":"2004","journal-title":"Front. Biosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S1359-6446(04)03333-1","article-title":"Transferrin: Structure, function and potential therapeutic actions","volume":"10","author":"Gomme","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1182\/blood-2014-12-617571","article-title":"TfR2 links iron metabolism and erythropoiesis","volume":"125","author":"Pantopoulos","year":"2015","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/0005-2795(76)90270-1","article-title":"The detection of four molecular forms of human transferrin during the iron binding process","volume":"453","author":"Makey","year":"1976","journal-title":"Biochim. Biophys. Acta Protein Struct."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.2174\/092986705774462969","article-title":"Structure\/Function Overview of Proteins Involved in Iron Storage and Transport","volume":"12","author":"Sargent","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/iub.1621","article-title":"Ferritin, cellular iron storage and regulation","volume":"69","author":"Arosio","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12223","DOI":"10.1021\/ic400484n","article-title":"Ferritin: The Protein Nanocage and Iron Biomineral in Health and in Disease","volume":"52","author":"Theil","year":"2013","journal-title":"Inorg. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0892-0354(92)90011-E","article-title":"Ferritin and hemosiderin in pathological tissues","volume":"5","author":"Iancu","year":"1992","journal-title":"Electron Microsc. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1021\/acs.biochem.7b00024","article-title":"Iron Oxidation and Core Formation in Recombinant Heteropolymeric Human Ferritins","volume":"56","author":"Mehlenbacher","year":"2017","journal-title":"Biochemistry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1159\/000496324","article-title":"Storage Iron Turnover from a New Perspective","volume":"141","author":"Saito","year":"2019","journal-title":"Acta Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.freeradbiomed.2018.06.037","article-title":"Transferrin and transferrin receptors update","volume":"133","author":"Kawabata","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.2174\/092986705774462996","article-title":"Molecular Mechanisms of Iron Uptake by Cells and the Use of Iron Chelators for the Treatment of Cancer","volume":"12","author":"Richardson","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1517\/13543784.2013.787408","article-title":"Potential clinical applications of chelating drugs in diseases targeting transferrin-bound iron and other metals","volume":"22","author":"Kontoghiorghe","year":"2013","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J., and Kontoghiorghe, C.N. (2020). Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases. Cells, 9.","DOI":"10.3390\/cells9061456"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1056\/NEJM199912233412607","article-title":"Disorders of Iron Metabolism","volume":"341","author":"Andrews","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1017\/S1368980008002401","article-title":"Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993\u20132005","volume":"12","author":"McLean","year":"2009","journal-title":"Public Health Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0140-6736(20)32594-0","article-title":"Iron deficiency","volume":"397","author":"Pasricha","year":"2021","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tardy, A.-L., Pouteau, E., Marquez, D., Yilmaz, C., and Scholey, A. (2020). Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients, 12.","DOI":"10.3390\/nu12010228"},{"key":"ref_25","unstructured":"Moustarah, F., and Mohiuddin, S.S. (2020). Dietary Iron, StatPearls Publishing."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s12098-019-03107-y","article-title":"Treating Iron Deficiency Anemia","volume":"86","author":"Chandra","year":"2019","journal-title":"Indian J. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1111\/ped.14237","article-title":"Ferrous sulfate oral solution in young children with iron deficiency anemia: An open-label trial of efficacy, safety, and acceptability","volume":"62","author":"Kubiak","year":"2020","journal-title":"Pediatr. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s12011-013-9797-2","article-title":"Is a 40% Absorption of Iron from a Ferrous ascorbate Reference Dose Appropriate to Assess Iron Absorption Independent of Iron Status?","volume":"155","author":"Valenzuela","year":"2013","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1007\/s12098-019-03068-2","article-title":"Comparison of Therapeutic Efficacy of Ferrous Ascorbate and Iron Polymaltose Complex in Iron Deficiency Anemia in Children: A Randomized Controlled Trial","volume":"86","author":"Patil","year":"2019","journal-title":"Indian J. Pediatr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"737","DOI":"10.2147\/CIA.S58394","article-title":"Ulceration of the oral mucosa following direct contact with ferrous sulfate in elderly patients: A case report and a review of the French National Pharmacovigilance Database","volume":"9","author":"Liabeuf","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tolkien, Z., Stecher, L., Mander, A.P., Pereira, D.I., and Powell, J.J. (2015). Ferrous sulfate supplementation causes significant gastro-intestinal side-effects in adults: A systematic review and meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117383"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1365-2125.1991.tb05525.x","article-title":"Iron supplements: A common cause of drug interactions","volume":"31","author":"Campbell","year":"1991","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G., Kolnagou, A., Demetriou, T., Neocleous, M., and Kontoghiorghe, C. (2021). New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115546"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/nyas.13008","article-title":"Iron and cancer: Recent insights","volume":"1368","author":"Manz","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.biopha.2012.06.003","article-title":"Treatment of mild non-chemotherapy-induced iron deficiency anemia in cancer patients: Comparison between oral ferrous bisglycinate chelate and ferrous sulfate","volume":"66","author":"Ferrari","year":"2012","journal-title":"Biomed. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100873","DOI":"10.1016\/j.mam.2020.100873","article-title":"Iron deficiency and supplementation in heart failure and chronic kidney disease","volume":"75","author":"Punj","year":"2020","journal-title":"Mol. Asp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1053\/j.ackd.2019.05.001","article-title":"Long-Term Risks of Intravenous Iron in End-Stage Renal Disease Patients","volume":"26","author":"Kshirsagar","year":"2019","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/ccr3.2595","article-title":"Recurrent severe hypophosphatemia following intravenous iron administration","volume":"8","author":"Nataatmadja","year":"2020","journal-title":"Clin. Case Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/bjh.17202","article-title":"Intravenous iron: Do we adequately understand the short- and long-term risks in clinical practice?","volume":"193","author":"Rund","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e342","DOI":"10.1016\/S2352-3026(19)30264-9","article-title":"Intravenous iron: A framework for changing the management of iron deficiency","volume":"7","author":"Auerbach","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2020041","DOI":"10.4084\/mjhid.2020.041","article-title":"Iron Deficiency Anemia in Children Residing in High and Low-Income Countries: Risk Factors, Prevention, Diagnosis and Therapy","volume":"12","author":"Mantadakis","year":"2020","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"783","DOI":"10.4103\/jfmpc.jfmpc_1062_19","article-title":"Prevalence of anaemia and its association with dietary habits among pregnant women in the urban area of Haryana","volume":"9","author":"Grover","year":"2020","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_43","unstructured":"(1983). Community control of hereditary anaemias: Memorandum from a WHO meeting. Bull. World Health Organ., 61, 63\u201380."},{"key":"ref_44","first-page":"704","article-title":"Inherited haemoglobin disorders: An increasing global health problem","volume":"79","author":"Weatherall","year":"2001","journal-title":"Bull. World Health Organ."},{"key":"ref_45","unstructured":"Modell, B., and Berdoukas, V. (1984). The Clinical Approach to Thalassaemia, Grune and Stratton."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Barton, J.C., and Edwards, C.Q. (2000). Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment, Cambridge University Press.","DOI":"10.1017\/CBO9780511666476"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/ng0896-399","article-title":"A novel MHC class I\u2013like gene is mutated in patients with hereditary haemochromatosis","volume":"13","author":"Feder","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1056\/NEJMra031573","article-title":"Hereditary Hemochromatosis\u2014A New Look at an Old Disease","volume":"350","author":"Pietrangelo","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2036.2004.02024.x","article-title":"Targeted screening for hereditary haemochromatosis in high-risk groups","volume":"20","author":"Dubois","year":"2004","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/BF02723953","article-title":"Burden of genetic disorders in india","volume":"67","author":"Verma","year":"2000","journal-title":"Indian J. Pediatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"197","DOI":"10.5662\/wjm.v4.i4.197","article-title":"Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases","volume":"4","author":"Kolnagou","year":"2014","journal-title":"World J. Methodol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.2174\/092986705774463003","article-title":"Advances in Iron Overload Therapies. Prospects for Effective Use of Deferiprone (L1), Deferoxamine, the New Experimental Chelators ICL670, GT56-252, L1NAll and their Combinations","volume":"12","author":"Kontoghiorghes","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.3324\/haematol.2009.009118","article-title":"Improved survival in thalassemia major patients on switching from desferrioxamine to combined chelation therapy with desferrioxamine and deferiprone","volume":"94","author":"Telfer","year":"2009","journal-title":"Haematologica"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1532-429X-10-12","article-title":"Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction","volume":"10","author":"Tanner","year":"2008","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/bjh.15595","article-title":"MRI multicentre prospective survey in thalassaemia major patients treated with defer-asirox versus deferiprone and desferrioxamine","volume":"183","author":"Pepe","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/17474086.2019.1593823","article-title":"Therapeutic mechanism of combined oral chelation therapy to maximize efficacy of iron removal in transfusion-dependent thalassemia major-a pilot study","volume":"12","author":"Lin","year":"2019","journal-title":"Expert Rev. Hematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.transci.2019.03.021","article-title":"A 1-year randomized trial of deferasirox alone versus deferasirox and deferoxamine combination for the treatment of iron overload in thalassemia major","volume":"58","author":"Eghbali","year":"2019","journal-title":"Transfus. Apher. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2165\/00002018-200326080-00003","article-title":"Benefits and risks of deferiprone in iron overload in thalassaemia and other conditions: Comparison of epidemiological and therapeutic aspects with deferoxamine","volume":"26","author":"Kontoghiorghes","year":"2003","journal-title":"Drug Saf."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"163","DOI":"10.5662\/wjm.v4.i3.163","article-title":"World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients","volume":"4","author":"Kontoghiorghe","year":"2014","journal-title":"World J. Methodol."},{"key":"ref_60","unstructured":"Kontoghiorghes, G.J. (1982). The Design of Orally Active Iron Chelators for the Treatment of Thalassaemia. [Ph.D. Thesis, University of Essex]. Available online: https:\/\/www.pri.ac.cy\/files\/KGJ_thesis_1982.pdf."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1749-6632.1990.tb24321.x","article-title":"Design, Properties, and Effective Use of the Oral Chelator L1 and Other Alpha-Ketohydroxypyridines in the Treatment of Transfusional Iron Overload in Thalassemia","volume":"612","author":"Kontoghiorghes","year":"1990","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.2174\/0929867043364685","article-title":"The Design and Development of Deferiprone (L1) and Other Iron Chelators for Clinical Use: Targeting Methods and Application Prospects","volume":"11","author":"Kontoghiorghes","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e2020011","DOI":"10.4084\/mjhid.2020.011","article-title":"The History of Deferiprone (L1) and the Paradigm of the Complete Treatment of Iron Overload in Thalassaemia","volume":"12","author":"Kontoghiorghes","year":"2020","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_64","unstructured":"Lamy, J. (1981). Invertebrate Oxygen Binding Proteins, Structure, Active Site and Function, Marcel Dekker."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"20841","DOI":"10.3390\/molecules201119725","article-title":"Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology","volume":"20","author":"Kontoghiorghe","year":"2015","journal-title":"Molecules"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0020-1693(00)80369-2","article-title":"Comparative iron binding studies of bis and tris (3-hydroxy-2-methylpyrid-4-ones) and desferrioxamine","volume":"188","author":"Sheppard","year":"1991","journal-title":"Inorg. Chim. Acta"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/S0140-6736(83)90413-0","article-title":"Desferrioxamine Suppositories","volume":"322","author":"Kontoghiorghes","year":"1983","journal-title":"Lancet"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0140-6736(85)91472-2","article-title":"New Orally Active Iron Chelators","volume":"325","author":"Kontoghiorghes","year":"1985","journal-title":"Lancet"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1136\/jcp.40.4.404","article-title":"Iron chelation studies using desferrioxamine and the potential oral chelator, 1,2-dimethyl-3-hydroxypyrid-4-one, in normal and iron loaded rats","volume":"40","author":"Kontoghiorghes","year":"1987","journal-title":"J. Clin. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1600-0609.1986.tb01773.x","article-title":"Dose response studies using desferrioxamine and orally active chelators in a mouse model","volume":"37","author":"Kontoghiorghes","year":"1986","journal-title":"Scand. J. Haematol."},{"key":"ref_71","first-page":"670","article-title":"Orally active alpha-ketohydroxypyridine iron chelators: Studies in mice","volume":"30","author":"Kontoghiorghes","year":"1986","journal-title":"Mol. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/j.1365-2141.1986.tb04082.x","article-title":"Orally active \u03b1-ketohydroxy pyridine iron chelators intended for clinical use: In Vivo studies in rabbits","volume":"62","author":"Kontoghiorghes","year":"1986","journal-title":"Br. J. Haematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1159\/000205877","article-title":"Orally Active Alpha-Ketohydroxypyridine Iron Chelators: Effects on Iron and Other Metal Mobilisations","volume":"78","author":"Kontoghiorghes","year":"1987","journal-title":"Acta Haematol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000205878","article-title":"In Vivo Evaluation of Hydroxypyridone Iron Chelators in a Mouse Model","volume":"78","author":"Gyparaki","year":"1987","journal-title":"Acta Haematol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"593","DOI":"10.3109\/03630268808991649","article-title":"Selection of Hydroxypyridin-4-Ones for the Treatment of Iron Overload Using In Vitro and In Vivo Models","volume":"12","author":"Huehns","year":"1988","journal-title":"Hemoglobin"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1182\/blood.V76.11.2389.2389","article-title":"Relative oral efficacy and acute toxicity of hydroxy-pyridin-4-one iron chelators in mice","volume":"76","author":"Porter","year":"1990","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/ajh.2830420403","article-title":"Selection of a new generation of orally active \u03b1-ketohydroxypyridine iron chelators intended for use in the treatment of iron overload","volume":"42","author":"Kontoghiorghes","year":"1993","journal-title":"Am. J. Hematol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"L11","DOI":"10.1016\/S0020-1693(00)85549-8","article-title":"Simple synthesis of the potent iron chelators 1-alkyl-3-hydroxy-2-methylpyrid-4-ones","volume":"136","author":"Kontoghiorghes","year":"1987","journal-title":"Inorg. Chim. Acta"},{"key":"ref_79","first-page":"1","article-title":"Oral chelation in the treatment of thalassaemia and other diseases","volume":"28","author":"Kontoghiorghes","year":"1992","journal-title":"Drugs Today"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/S0140-6736(87)90545-9","article-title":"1,2-Dimethyl-3-Hydroxypyrid-4-One, an Orally Active Chelator for Treatment of Iron Overload","volume":"329","author":"Kontoghiorghes","year":"1987","journal-title":"Lancet"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1136\/bmj.295.6612.1509","article-title":"Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one","volume":"295","author":"Kontoghiorghes","year":"1987","journal-title":"BMJ"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1136\/bmj.296.6637.1672-c","article-title":"Iron chelating drugs","volume":"296","author":"Kontoghiorghes","year":"1988","journal-title":"BMJ"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1136\/bmj.303.6813.1279","article-title":"Oral iron chelation is here","volume":"303","author":"Kontoghiorghes","year":"1991","journal-title":"BMJ"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/978-1-4615-2554-7_38","article-title":"Lessons from Preclinical and Clinical Studies with 1,2-Diethyl-3-Hydroxypyridin-4-One, CP94 and Related Compounds","volume":"Volume 356","author":"Porter","year":"1994","journal-title":"Progress in Iron Research"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1365-2141.1993.tb08660.x","article-title":"Contrasting interspecies efficacy and toxicology of 1, 2-diethy 1\u20133 -hydroxypyridin-4-one, CP94, relates to differing metabolism of the iron chelating site","volume":"85","author":"Porter","year":"1993","journal-title":"Br. J. Haematol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/0731-7085(94)E0027-X","article-title":"HPLC determination of 1,2-diethyl-3-hydroxypyridin-4-one (CP94), its iron complex [Fe(III) (CP94)3] and glucuronide conjugate [CP94-GLUC] in serum and urine of thalassaemic patients","volume":"12","author":"Epemolu","year":"1994","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_87","first-page":"1480","article-title":"Future of oral iron chelator deferiprone (L1)","volume":"341","author":"Pfannkuch","year":"1993","journal-title":"Lancet"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/0140-6736(93)92443-W","article-title":"Toxicity of oral iron chelator L1","volume":"341","author":"Berdoukas","year":"1993","journal-title":"Lancet"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/0140-6736(93)92444-X","article-title":"Development of oral iron chelator L1","volume":"341","author":"Hershko","year":"1993","journal-title":"Lancet"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/0140-6736(93)92348-W","article-title":"Misinformation about deferiprone (L1)","volume":"342","author":"Kontoghiorghes","year":"1993","journal-title":"Lancet"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0140-6736(05)73574-1","article-title":"Deferiprone for thalassaemia","volume":"356","author":"Kontoghiorghes","year":"2000","journal-title":"Lancet"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/S0140-6736(05)74089-7","article-title":"Deferiprone for thalassaemia","volume":"356","author":"Pippard","year":"2000","journal-title":"Lancet"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S0140-6736(05)71812-2","article-title":"Deferiprone or fatal iron toxic effects?","volume":"357","author":"Kontoghiorghes","year":"2001","journal-title":"Lancet"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0140-6736(89)90641-7","article-title":"Agranulocytosis and Thrombocytopenia in Patient with Blackfan-Diamond Anaemia during Oral Chelator Trial","volume":"334","author":"Hoffbrand","year":"1989","journal-title":"Lancet"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1365-2141.1992.tb06445.x","article-title":"Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassaemia: Indian trial","volume":"82","author":"Agarwal","year":"1992","journal-title":"Br. J. Haematol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/BF02751425","article-title":"Present status and future prospects of oral iron chelation therapy in thalassaemia and other diseases","volume":"60","author":"Kontoghiorghes","year":"1993","journal-title":"Indian J. Pediatr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1182\/blood-2002-10-3280","article-title":"Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone","volume":"102","author":"Cohen","year":"2003","journal-title":"Blood"},{"key":"ref_98","unstructured":"(2019, October 01). The History of Deferiprone. Available online: https:\/\/www.youtube.com\/watch?v=ZcvSLyIgYd8."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/j.1365-2141.1990.tb07887.x","article-title":"L1 (1,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassaemia major","volume":"76","author":"Kontoghiorghes","year":"1990","journal-title":"Br. J. Haematol."},{"key":"ref_100","first-page":"101","article-title":"Studies of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one in thalassemia patients","volume":"27","author":"Olivieri","year":"1990","journal-title":"Semin. Hematol."},{"key":"ref_101","first-page":"2133","article-title":"Long-term treatment of patients with transfusion hemosiderosis using oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1)","volume":"135","author":"Goudsmit","year":"1991","journal-title":"Ned. Tijdschr. Geneeskd."},{"key":"ref_102","first-page":"273","article-title":"New therapeutic trends in thalassemia: Oral chelating agents","volume":"14","author":"Carnelli","year":"1992","journal-title":"Pediatr. Med. Chir."},{"key":"ref_103","first-page":"586","article-title":"Treatment of iron overload states with oral administration of the chelator agent, L1 (Deferiprone)","volume":"40","author":"Brabec","year":"1994","journal-title":"Vnitr. Lek."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s002770050236","article-title":"Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): A Dutch multicenter trial","volume":"73","author":"Kersten","year":"1996","journal-title":"Ann. Hematol."},{"key":"ref_105","first-page":"1005","article-title":"Royal Society of Chemistry-sixth international symposium on applied bioinorganic chemistry","volume":"4","author":"Taylor","year":"2001","journal-title":"IDrugs Investig. Drugs J."},{"key":"ref_106","first-page":"115","article-title":"Chelation therapy in patients with thalassemia using the orally active iron chelator deferiprone (L1)","volume":"85","author":"Rombos","year":"2000","journal-title":"Haematologica"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/15376516.2012.720305","article-title":"The Proceedings of the 20th International Conference on Chelation held in the USA: Advances on new and old chelation therapies","volume":"23","author":"Kontoghiorghes","year":"2013","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1136\/bmj.328.7436.358","article-title":"Thalassaemia major: The murky story of deferiprone","volume":"328","author":"Savulescu","year":"2004","journal-title":"BMJ"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/S0140-6736(03)13309-0","article-title":"Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: A randomised, double-blind, placebo-controlled, dose-escalation trial","volume":"361","author":"Olivieri","year":"2003","journal-title":"Lancet"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1182\/blood-2006-02-002394","article-title":"Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: New data, new questions","volume":"107","author":"Neufeld","year":"2006","journal-title":"Blood"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1517\/14728214.11.1.1","article-title":"New chelation therapies and emerging chelating drugs for the treatment of iron overload","volume":"11","author":"Kontoghiorghes","year":"2006","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ajh.23386","article-title":"Deferiprone (GPO-L-ONE\u00ae) monotherapy reduces iron overload in transfusion-dependent thalassemias: 1-year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO-L-ONE.; A001) from Thailand","volume":"88","author":"Viprakasit","year":"2013","journal-title":"Am. J. Hematol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/ejh.12939","article-title":"The aim of iron chelation therapy in thalassaemia","volume":"99","author":"Kontoghiorghes","year":"2017","journal-title":"Eur. J. Haematol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e469","DOI":"10.1016\/S2352-3026(20)30100-9","article-title":"Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): A multicentre, randomised, open-label, non-inferiority, phase 3 trial","volume":"7","author":"Maggio","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_115","first-page":"261","article-title":"A synopsis of current care of thalassaemia major patients in Hong Kong","volume":"17","author":"Au","year":"2011","journal-title":"Hong Kong Med. J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.bcmd.2011.07.002","article-title":"Iron chelation therapy in thalassemia major: A systematic review with meta-analyses of 1520 patients included on randomized clinical trials","volume":"47","author":"Maggio","year":"2011","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1046\/j.1365-2141.2000.01866.x","article-title":"Safety profile of the oral iron chelator deferiprone: A mul-ticentre study","volume":"108","author":"Cohen","year":"2000","journal-title":"Br. J. Haematol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/ajh.23219","article-title":"Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients","volume":"87","author":"Maggio","year":"2012","journal-title":"Am. J. Hematol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/j.1600-0609.2010.01499.x","article-title":"Reduction of body iron stores to normal range levels in thalassaemia by using a deferiprone\/deferoxamine combination and their maintenance thereafter by deferiprone monotherapy","volume":"85","author":"Kolnagou","year":"2010","journal-title":"Eur. J. Haematol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"465","DOI":"10.2147\/DDDT.S79458","article-title":"Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes","volume":"10","author":"Kontoghiorghes","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"18","DOI":"10.31083\/j.fbe1403018","article-title":"Benefits and Risks in Polypathology and Polypharmacotherapy Chal-lenges in the Era of the Transition of Thalassaemia from a Fatal to a Chronic or Curable Disease","volume":"14","author":"Kolnagou","year":"2022","journal-title":"Front. Biosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1055\/s-0043-102691","article-title":"Prevention of Iron Overload and Long Term Maintenance of Normal Iron Stores in Thalassaemia Major Patients using Deferiprone or Deferiprone Deferoxamine Combination","volume":"67","author":"Kolnagou","year":"2017","journal-title":"Drug Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.2741\/4634","article-title":"Chelation protocols for the elimination and prevention of iron overload in thalassaemia","volume":"23","author":"Kolnagou","year":"2018","journal-title":"Front. Biosci."},{"key":"ref_124","first-page":"1332","article-title":"Chelators affecting iron absorption in mice","volume":"40","author":"Kontoghiorghes","year":"1990","journal-title":"Arzneimittelforschung"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.2042-7158.1987.tb06249.x","article-title":"Effects of the pyrones, maltol and ethyl maltol, on iron absorption from the rat small intestine","volume":"39","author":"Barrand","year":"1987","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1111\/j.1476-5381.1991.tb12240.x","article-title":"Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the rat","volume":"102","author":"Barrand","year":"1991","journal-title":"Br. J. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1039\/b416256k","article-title":"Metal complexes of maltol and close analogues in medicinal inorganic chemistry","volume":"35","author":"Thompson","year":"2006","journal-title":"Chem. Soc. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1046\/j.1365-2036.1998.00380.x","article-title":"Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron","volume":"12","author":"Harvey","year":"1998","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1177\/000456320003700405","article-title":"Assessment of iron absorption from ferric trimaltol","volume":"37","author":"Reffitt","year":"2000","journal-title":"Ann. Clin. Biochem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1177\/1060028020941014","article-title":"Ferric Maltol: A New Oral Iron Formulation for the Treatment of Iron Deficiency in Adults","volume":"55","author":"Khoury","year":"2021","journal-title":"Ann. Pharmacother."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1517\/14656566.2015.1096929","article-title":"Ferric maltol (ST10): A novel oral iron supplement for the treatment of iron deficiency anemia in inflammatory bowel disease","volume":"16","author":"Stallmach","year":"2015","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1097\/MIB.0000000000000648","article-title":"Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment","volume":"22","author":"Murawska","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1053\/j.ackd.2019.05.002","article-title":"Novel Oral Iron Therapies for Iron Deficiency Anemia in Chronic Kidney Disease","volume":"26","author":"Pergola","year":"2019","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s13318-016-0334-5","article-title":"Randomized Open-Label Phase 1 Study of the Pharmacokinetics of Ferric Maltol in Inflammatory Bowel Disease Patients with Iron Deficiency","volume":"42","author":"Bokemeyer","year":"2017","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/MIB.0000000000000314","article-title":"AEGIS Study Group. Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: Results from a phase-3 clinical trial program","volume":"21","author":"Gasche","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/apt.13665","article-title":"Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: Long-term extension data from a Phase 3 study","volume":"44","author":"Schmidt","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1365-2710.1991.tb00292.x","article-title":"Absorption of low and therapeutic doses of ferric maltol, a novel ferric iron compound, in iron deficient subjects using a single dose iron absorption test","volume":"16","author":"Kelsey","year":"1991","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2000616","DOI":"10.1183\/13993003.00616-2020","article-title":"Oral iron supplementation with ferric maltol in patients with pulmonary hypertension","volume":"56","author":"Olsson","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_139","first-page":"70","article-title":"Efficacy and safety of oral ferric maltol (FM) in treating iron-deficiency anemia (IDA) in patients with CKD: Randomized controlled trial [FR-OR120]","volume":"29","author":"Kopyt","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1092704","DOI":"10.3389\/fimmu.2022.1092704","article-title":"Intravenous iron supplementation in heart failure patients induces temporary endothelial dysfunction with release of endothelial microvesicles","volume":"13","author":"Mause","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s12325-022-02367-z","article-title":"Preferences for Anaemia Treatment Attributes among Patients with Non-Dialysis-Dependent Chronic Kidney Disease","volume":"40","author":"Alexandre","year":"2023","journal-title":"Adv. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Ogawa, C., Tsuchiya, K., Kanemitsu, M., and Maeda, K. (2022). Low-Dose Oral Iron Replacement Therapy Is Effective for Many Japanese Hemodialysis Patients: A Retrospective Observational Study. Nutrients, 15.","DOI":"10.3390\/nu15010125"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"114364","DOI":"10.1016\/j.ecoenv.2022.114364","article-title":"Ferric citrate-induced colonic mucosal damage associated with oxidative stress, inflammation responses, apoptosis, and the changes of gut microbial composition","volume":"249","author":"Xia","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5662\/wjm.v6.i1.1","article-title":"New developments and controversies in iron metabolism and iron chelation therapy","volume":"6","author":"Kontoghiorghe","year":"2016","journal-title":"World J. Methodol."},{"key":"ref_145","first-page":"e441","article-title":"Patent rulings raise hope for cheap cancer drugs in India","volume":"14","author":"Sharma","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2165\/11587120-000000000-00000","article-title":"Iron-chelating therapies in a transfusion-dependent thalassaemia population in Thailand: A cost-effectiveness study","volume":"31","author":"Luangasanatip","year":"2011","journal-title":"Clin. Drug Investig."},{"key":"ref_147","first-page":"9","article-title":"Oral iron chelation with 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron loaded thalassemia patients","volume":"12","author":"Olivieri","year":"1993","journal-title":"Bone Marrow Transpl."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"112381","DOI":"10.1016\/j.biopha.2021.112381","article-title":"Iron chelation therapy with de-feriprone improves oxidative status and red blood cell quality and reduces redox-active iron in \u03b2-thalassemia\/hemoglobin E patients","volume":"145","author":"Morales","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"346","DOI":"10.3109\/03630260903212563","article-title":"Treatment with Deferiprone for Iron Overload Alleviates Bone Marrow Failure in a Fanconi Anemia Patient","volume":"33","author":"Chang","year":"2009","journal-title":"Hemoglobin"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.leukres.2013.07.021","article-title":"A comparative study of deferasirox and deferiprone in the treatment of iron overload in patients with myelodysplastic syndromes","volume":"37","author":"Cermak","year":"2013","journal-title":"Leuk. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1574.e1","DOI":"10.1016\/j.cjca.2016.07.589","article-title":"Successful Treatment of Iron-Overload Cardiomyopathy in Hereditary Hemochromatosis with Deferoxamine and Deferiprone","volume":"32","author":"Jirsa","year":"2016","journal-title":"Can. J. Cardiol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3109\/03630269.2010.486335","article-title":"Iron chelation therapy in hereditary hemochromatosis and thalassemia intermedia: Regulatory and non regulatory mechanisms of increased iron absorption","volume":"34","author":"Kontoghiorghes","year":"2010","journal-title":"Hemoglobin"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1182\/blood-2006-04-016949","article-title":"Reversal of cardiac complications by deferiprone and deferoxamine combination therapy in a patient affected by a severe type of juvenile hemochromatosis (JH)","volume":"109","author":"Fabio","year":"2007","journal-title":"Blood"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1182\/bloodadvances.2021006778","article-title":"Deferiprone for transfusional iron overload in sickle cell disease and other anemias: Open-label study of up to 3 years","volume":"7","author":"Elalfy","year":"2022","journal-title":"Blood Adv."},{"key":"ref_155","first-page":"522","article-title":"Studies of aluminium mobilization in renal dialysis patients using the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one","volume":"44","author":"Kontoghiorghes","year":"1994","journal-title":"Arzneimittelforschung"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0378-4274(95)03415-H","article-title":"Comparative efficacy and toxicity of desferrioxamine, deferiprone and other iron and aluminium chelating drugs","volume":"80","author":"Kontoghiorghes","year":"1995","journal-title":"Toxicol. Lett."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13023-020-01385-w","article-title":"Effects of iron chelation therapy on the clinical course of aceruloplasminemia: An analysis of aggregated case reports","volume":"15","author":"Vroegindeweij","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1182\/blood-2006-12-065433","article-title":"Selective iron chelation in Friedreich ataxia: Biologic and clinical implications","volume":"110","author":"Boddaert","year":"2007","journal-title":"Blood"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.3324\/haematol.2011.043018","article-title":"A pilot trial of deferiprone for neurodegeneration with brain iron accumulation","volume":"96","author":"Abbruzzese","year":"2011","journal-title":"Haematologica"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/s41598-017-01402-2","article-title":"Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson\u2019s disease","volume":"7","author":"Ward","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s11064-014-1508-7","article-title":"Characterization of the Neuroprotective Potential of Derivatives of the Iron Chelating Drug Deferiprone","volume":"40","author":"Maher","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Romano, N., Baiardi, G., Pinto, V.M., Quintino, S., Gianesin, B., Sasso, R., Diociasi, A., Mattioli, F., Marchese, R., and Abbruzzese, G. (2022). Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy. J. Clin. Med., 11.","DOI":"10.3390\/jcm11154524"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3109\/15376516.2012.730558","article-title":"Effect of deferiprone, an oral iron chelator, in diabetic and non-diabetic glomerular disease","volume":"23","author":"Rajapurkar","year":"2013","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_164","first-page":"17","article-title":"Deferiprone (L1) as an adjuvant therapy for Plasmodium falciparum malaria","volume":"115","author":"Mohanty","year":"2002","journal-title":"Indian J. Med. Res."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Saxena, D., Spino, M., Tricta, F., Connelly, J., Cracchiolo, B.M., Hanauske, A.R., D\u2019Alliessi Gandolfi, D., Mathews, M.B., Karn, J., and Holland, B. (2016). Drug-Based Lead Discovery: The Novel Ablative An-tiretroviral Profile of Deferiprone in HIV-1-Infected Cells and in HIV-Infected Treatment-Naive Subjects of a Double-Blind, Placebo-Controlled, Randomized Exploratory Trial. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154842"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/S0140-6736(89)92011-4","article-title":"Efficacy and Safety of Oral Iron Chelator L1 in Anaemic Rheumatoid Arthritis Patients","volume":"334","author":"Vreugdenhil","year":"1989","journal-title":"Lancet"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/ane.12141","article-title":"Triple therapy with deferiprone, idebenone and riboflavin in Friedreich\u2019s ataxia-open-label trial","volume":"129","author":"Arpa","year":"2014","journal-title":"Acta Neurol. Scand."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1056\/NEJMoa2209254","article-title":"Trial of Deferiprone in Parkinson\u2019s Disease","volume":"387","author":"Devos","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1365-2141.1990.tb07887.x","article-title":"Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) I. Iron Chelation and Metabolic Studies","volume":"76","author":"Kontoghiorghes","year":"1990","journal-title":"Br. J. Haematol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/clpt.1990.147","article-title":"Pharmacokinetic studies in humans with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one","volume":"48","author":"Kontoghiorghes","year":"1990","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/13543784.2019.1631284","article-title":"Prospects for the introduction of targeted antioxidant drugs for the prevention and treatment of diseases related to free radical pathology","volume":"28","author":"Kontoghiorghes","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"862","DOI":"10.2741\/4253","article-title":"Antioxidant targeting by deferiprone in diseases related to oxidative damage","volume":"19","author":"Kontoghiorghe","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J. (2022). New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213990"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1158\/1535-7163.MCT-17-1009","article-title":"Gallium Maltolate Disrupts Tumor Iron Metabolism and Retards the Growth of Glioblastoma by Inhibiting Mitochondrial Function and Ribonucleotide Reductase","volume":"17","author":"Chitambar","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"585","DOI":"10.2174\/187152011796011046","article-title":"Hepatocellular carcinoma detection by gallium scan and subsequent treatment by gallium maltolate: Rationale and case study","volume":"11","author":"Bernstein","year":"2011","journal-title":"Anti Cancer Agents Med. Chem."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/jid.2014.476","article-title":"Gallium Maltolate Inhibits Human Cutaneous T-Cell Lymphoma Tumor Development in Mice","volume":"135","author":"Wu","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1021\/acsomega.7b02026","article-title":"Indium\/Gallium Maltolate Effects on Human Breast Carcinoma Cells: In Vitro Investigation on Cytotoxicity and Synergism with Mitoxantrone","volume":"3","author":"Merli","year":"2018","journal-title":"ACS Omega"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.vetmic.2011.09.009","article-title":"Antimicrobial activity of gallium maltolate against Staphylococcus aureus and methicillin-resistant S. aureus and Staphylococcus pseudintermedius: An in vitro study","volume":"155","author":"Arnold","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.tvjl.2014.06.023","article-title":"Comparison of the antimicrobial activities of gallium nitrate and gallium maltolate against Mycobacterium avium subsp. paratuberculosis in vitro","volume":"202","author":"Fecteau","year":"2014","journal-title":"Vet. J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fcimb.2018.00316","article-title":"Antimicrobial Activity of Gallium Compounds on ESKAPE Pathogens","volume":"8","author":"Hijazi","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"5197","DOI":"10.1128\/AAC.00616-13","article-title":"Synchrotron X-ray Fluorescence Microscopy of Gallium in Bladder Tissue following Gallium Maltolate Administration during Urinary Tract Infection","volume":"57","author":"Ball","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/0024-3205(92)90279-X","article-title":"Iron depletion: A defense against intracellular infection and neoplasm","volume":"50","author":"Weinberg","year":"1992","journal-title":"Life Sci."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0268-960X(95)90038-1","article-title":"Iron: Mammalian defense systems, mechanisms of disease, and chelation therapy approaches","volume":"9","author":"Kontoghiorghes","year":"1995","journal-title":"Blood Rev."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3109\/03630269.2010.483662","article-title":"The Role of Iron and Chelators on Infections in Iron Overload and Non Iron Loaded Conditions: Prospects for the Design of New Antimicrobial Therapies","volume":"34","author":"Kontoghiorghes","year":"2010","journal-title":"Hemoglobin"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J. (2020). Advances on Chelation and Chelator Metal Complexes in Medicine. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072499"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/03630260701727119","article-title":"Chelators Controlling Metal Metabolism and Toxicity Pathways: Applications in Cancer Prevention, Diagnosis and Treatment","volume":"32","author":"Kontoghiorghes","year":"2008","journal-title":"Hemoglobin"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.phrs.2016.11.009","article-title":"The therapeutic potential of iron-targeting gallium compounds in human disease: From basic research to clinical application","volume":"115","author":"Chitambar","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"302","DOI":"10.2174\/0929867324666170705120809","article-title":"Exploiting Cancer Metal Metabolism using Anti-Cancer Metal-Binding Agents","volume":"26","author":"Merlot","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_189","first-page":"755","article-title":"Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines","volume":"24","author":"Yasumoto","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1016\/j.bbamcr.2016.04.027","article-title":"Gallium and its competing roles with iron in biological systems","volume":"1863","author":"Chitambar","year":"2016","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"103406","DOI":"10.1016\/j.etap.2020.103406","article-title":"Role of mGluR 1 in synaptic plasticity impairment induced by maltol aluminium in rats","volume":"78","author":"Pan","year":"2020","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1248\/bpb.30.1390","article-title":"Involvement of NO generation in aluminum-induced cell death","volume":"30","author":"Satoh","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/s12011-018-1496-6","article-title":"Biocompatibility Studies of Gadolinium Complexes with Iminodiacetic Acid Derivatives","volume":"189","author":"Sikora","year":"2019","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2967\/jnmt.118.217455","article-title":"Bilateral Orbital Soft-Tissue Metastases from Renal Neuroendocrine Tumor: Successful Theranostic Application of 68Ga\/177Lu-DOTATATE with Improvement of Vision","volume":"47","author":"Parghane","year":"2019","journal-title":"J. Nucl. Med. Technol."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Imberti, C., Adumeau, P., Blower, J.E., Al Salemee, F., Torres, J.B., Lewis, J.S., Zeglis, B.M., Terry, S.Y.A., and Blower, P.J. (2020). Manipu-lating the In Vivo Behaviour of 68Ga with Tris (Hydroxypyridinone) Chelators: Pretargeting and Blood Clearance. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041496"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.2460\/ajvr.68.10.1041","article-title":"Pharmacokinetics of gallium maltolate after intragastric administration in neonatal foals","volume":"68","author":"Martens","year":"2007","journal-title":"Am. J. Vet. Res."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2460\/ajvr.77.2.151","article-title":"Serum and tissue concentrations of gallium after oral ad-ministration of gallium nitrate and gallium maltolate to neonatal calves","volume":"77","author":"Monk","year":"2016","journal-title":"Am. J. Vet. Res."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/jvp.12022","article-title":"Reduction in absorption of gallium maltolate in adult horses following oral administration with food: Chemistry and pharmacokinetics","volume":"36","author":"Pollina","year":"2013","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/jvp.12114","article-title":"Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits","volume":"37","author":"Sampieri","year":"2014","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Gaur, K., V\u00e1zquez-Salgado, A.M., Duran-Camacho, G., Dominguez-Martinez, I., Benjam\u00edn-Rivera, J.A., Fern\u00e1ndez-Vega, L., Carmona Sarabia, L., Cruz Garc\u00eda, A., P\u00e9rez-Deliz, F., and M\u00e9ndez Rom\u00e1n, J.A. (2018). Iron and Copper Intracellular Chelation as an Anticancer Drug Strategy. Inorganics, 6.","DOI":"10.3390\/inorganics6040126"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s00432-017-2457-8","article-title":"Clinical Pharmacology and Clinical Trials of Ribonucleotide Reductase Inhibitors: Is It a Viable Cancer Therapy?","volume":"143","author":"Mannargudi","year":"2017","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1016\/S0021-9258(18)32582-1","article-title":"Mechanism of inhibition of mammalian ribonucleotide reductase by the iron chelate of 1-formylisoquinoline thiosemicarbazone. Destruction of the tyrosine free radical of the enzyme in an oxygen-requiring reaction","volume":"258","author":"Thelander","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_203","first-page":"29","article-title":"Cytotoxic Mechanisms of Iron Chelators","volume":"28","author":"Ganeshaguru","year":"1992","journal-title":"Drugs Today"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"18748","DOI":"10.18632\/oncotarget.4349","article-title":"Targeting cancer by binding iron: Dissecting cellular signaling pathways","volume":"6","author":"Lui","year":"2015","journal-title":"Oncotarget"},{"key":"ref_205","first-page":"2925","article-title":"Comparison of antineuroblastoma activity of desferrioxamine with that of oral iron chelators","volume":"49","author":"Blatt","year":"1989","journal-title":"Cancer Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/03630260600642450","article-title":"Iron Mobilization from Transferrin and Non-Transferrin-Bound-Iron by Deferiprone. Implications in the Treatment of Thalassemia, Anemia of Chronic Disease, Cancer and Other Conditions","volume":"30","author":"Kontoghiorghes","year":"2006","journal-title":"Hemoglobin"},{"key":"ref_207","first-page":"109","article-title":"The development of awareness of the carcinogenic hazard of inhaled iron","volume":"11","author":"Weinberg","year":"1999","journal-title":"Oncol. Res."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s00018-016-2194-1","article-title":"Mechanisms of ferroptosis","volume":"73","author":"Cao","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41392-022-01046-3","article-title":"Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immuno-therapy","volume":"7","author":"Gao","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41568-022-00459-0","article-title":"Targeting ferroptosis as a vulnerability in cancer","volume":"22","author":"Lei","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/s41419-022-04927-1","article-title":"Regulatory pathways and drugs associated with ferroptosis in tumors","volume":"13","author":"Wang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41419-022-04775-z","article-title":"Interaction between macrophages and ferroptosis","volume":"13","author":"Yang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"203","DOI":"10.31083\/j.fbl2707203","article-title":"Targeting the Macrophage-Ferroptosis Crosstalk: A Novel Insight into Tumor Immunotherapy","volume":"27","author":"Zhou","year":"2022","journal-title":"Front. Biosci."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"837249","DOI":"10.3389\/fphar.2022.837249","article-title":"Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases","volume":"13","author":"Miao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1530\/JME-13-0090","article-title":"Hypoxia upregulates the gene expression of mitochondrial aconitase in prostate carcinoma cells","volume":"51","author":"Tsui","year":"2013","journal-title":"J. Mol. Endocrinol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1476-4598-5-14","article-title":"Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues","volume":"5","author":"Singh","year":"2006","journal-title":"Mol. Cancer"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cell.2016.07.002","article-title":"Mitochondria and Cancer","volume":"166","author":"Vyas","year":"2016","journal-title":"Cell"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"608201","DOI":"10.3389\/fonc.2021.608201","article-title":"Discovery and Pharmacological Evaluation of STEAP4 as a Novel Target for HER2 Overexpressing Breast Cancer","volume":"11","author":"Orfanou","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Chekmarev, J., Azad, M.G., and Richardson, D.R. (2021). The Oncogenic Signaling Disruptor, NDRG1: Molecular and Cellular Mechanisms of Activity. Cells, 10.","DOI":"10.3390\/cells10092382"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"9125","DOI":"10.1158\/0008-5472.CAN-07-1525","article-title":"Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1\/Sp1 binding site in the promoter","volume":"67","author":"Zhang","year":"2007","journal-title":"Cancer Res."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"e3712","DOI":"10.1002\/nbm.3712","article-title":"Inhibition of prostate cancer proliferation by Deferiprone","volume":"30","author":"Veeraperumal","year":"2017","journal-title":"NMR Biomed."},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Fiorillo, M., T\u00f3th, F., Brindisi, M., Sotgia, F., and Lisanti, M.P. (2020). Deferiprone (DFP) Targets Cancer Stem cell (CSC) Propagation by Inhibiting Mitochondrial Metabolism and Inducing ROS Production. Cells, 9.","DOI":"10.3390\/cells9061529"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/00000421-199208000-00009","article-title":"Deferoxamine, cyclophosphamide, etoposide, carboplatin and thotepa (DCECaT): A new cytoreductive chelation-chemotherapy regimen in patients with advanced neuroblastoma","volume":"15","author":"Donfrancesco","year":"1992","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/ng1060","article-title":"A molecular signature of metastasis in primary solid tumours","volume":"33","author":"Ramaswamy","year":"2003","journal-title":"Nature Genet."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/0014-5793(86)80813-4","article-title":"Cytotoxic effects of the lipophilic iron chelator omadine","volume":"204","author":"Kontoghiorghes","year":"1986","journal-title":"FEBS Lett."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1007\/s00204-022-03287-1","article-title":"Reversal of genetic brain iron accumulation by N,N\u2032-bis(2-mercaptoethyl)isophthalamide, a lipophilic metal chelator, in mice","volume":"96","author":"Cheng","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/hon.2900040303","article-title":"Cytotoxic and DNA-inhibitory effects of iron chelators on human leukaemic cell lines","volume":"4","author":"Kontoghiorghes","year":"1986","journal-title":"Hematol. Oncol."},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J. (2022). Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126735"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"CNS90","DOI":"10.2217\/cns-2021-0018","article-title":"Undesired impact of iron supplement on MRI assessment of post-treatment glioblastoma","volume":"11","author":"Park","year":"2022","journal-title":"CNS Oncol."},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Talboom, K., Borstlap, W.A.A., Roodbeen, S.X., Bruns, E.R.J., Buskens, C.J., Hompes, R., Tytgat, K.M.A.J., Tuynman, J.B., Consten, E.C.J., and Heuff, G. (Lancet Haematol., 2023). FIT collaborative group. Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): A multicentre, open-label, randomised, controlled trial, Lancet Haematol.","DOI":"10.1016\/S2352-3026(22)00402-1"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/17474086.2020.1719359","article-title":"How to manage iron toxicity in post-allogeneic hematopoietic stem cell transplantation?","volume":"13","author":"Kontoghiorghes","year":"2020","journal-title":"Expert Rev. Hematol."},{"key":"ref_234","first-page":"27","article-title":"Advances in oral iron chelation in man","volume":"55","author":"Kontoghiorghes","year":"1992","journal-title":"Int. J. Hematol."},{"key":"ref_235","first-page":"ELT04","article-title":"Effective new treatments of iron overload in thalassaemia using the ICOC combination therapy protocol of deferiprone (L1) and deferoxamine and of new chelating drugs","volume":"91","author":"Kontoghiorghes","year":"2006","journal-title":"Haematologica"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/03630260701727085","article-title":"Long Term Comparative Studies in Thalassemia Patients Treated with Deferoxamine or a Deferoxamine\/Deferiprone Combination. Identification of Effective Chelation Therapy Protocols","volume":"32","author":"Kolnagou","year":"2008","journal-title":"Hemoglobin"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Kontoghiorghes, G.J., Kolnagou, A., Kontoghiorghe, C.N., Mourouzidis, L., Timoshnikov, V.A., and Polyakov, N.E. (2020). Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications. Medicines, 7.","DOI":"10.3390\/medicines7080045"},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Timoshnikov, V.A., Kobzeva, T.V., Polyakov, N.E., and Kontoghiorghes, G.J. (2020). Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113967"},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Timoshnikov, V.A., Selyutina, O.Y., Polyakov, N.E., Didichenko, V., and Kontoghiorghes, G.J. (2022). Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant\/Pro-Oxidant Activity and Applications in Medicine. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031247"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3109\/03630269.2011.578950","article-title":"Interactions of Hydroxycarbamide (Hydroxyurea) with Iron and Copper: Implications on Toxicity and Therapeutic Strategies","volume":"35","author":"Konstantinou","year":"2011","journal-title":"Hemoglobin"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"490","DOI":"10.7326\/0003-4819-120-6-199403150-00008","article-title":"Iron-Chelating Agents in Non-Iron Overload Conditions","volume":"120","author":"Voest","year":"1994","journal-title":"Ann. Intern. Med."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"e02284-19","DOI":"10.1128\/AAC.02284-19","article-title":"Lactoferrin Is Broadly Active against Yeasts and Highly Synergistic with Amphotericin B","volume":"64","author":"Fernandes","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_243","doi-asserted-by":"crossref","unstructured":"Rosa, L., Cutone, A., Lepanto, M.S., Paesano, R., and Valenti, P. (2017). Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091985"},{"key":"ref_244","first-page":"301.e1\u20138","article-title":"Lactoferrin: Structure, function and applications","volume":"33","year":"2009","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"e2913","DOI":"10.1038\/cddis.2017.284","article-title":"Platinum pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via DUB inhibition-dependent caspase activation and Bcr-Abl downregulation","volume":"8","author":"Lan","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13046-017-0547-8","article-title":"Platinum-containing compound platinum pyrithione suppresses ovarian tumor proliferation through proteasome inhibition","volume":"36","author":"Huang","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.1016\/j.bmcl.2015.07.065","article-title":"Discovery of 1-hydroxypyridine-2-thiones as selective histone deacetylase inhibitors and their potential application for treating leukemia","volume":"25","author":"Muthyala","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1021\/acs.molpharmaceut.8b01154","article-title":"Transport of the Ruthenium Complex [Ru(GA)(dppe)2]PF6 into Triple-Negative Breast Cancer Cells Is Facilitated by Transferrin Receptors","volume":"16","author":"Naves","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"45597","DOI":"10.18632\/oncotarget.17316","article-title":"Enhanced antitumor efficacy of cisplatin for treating ovarian cancer in vitro and in vivo via transferrin binding","volume":"8","author":"Peng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.2174\/092986705774463030","article-title":"Molecular factors and mechanisms affecting iron and other metal excretion or absorption in health and disease. The role of natural and synthetic chelators","volume":"12","author":"Kontoghiorghes","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1182\/blood.V72.1.358.358","article-title":"Antimalarial properties of orally active iron chelators","volume":"72","author":"Heppner","year":"1988","journal-title":"Blood"},{"key":"ref_252","doi-asserted-by":"crossref","unstructured":"Baldari, S., Di Rocco, G., and Toietta, G. (2020). Current Biomedical Use of Copper Chelation Therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031069"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"9120","DOI":"10.1021\/ic9004642","article-title":"Mixed-ligand copper (II) maltolate complexes: Synthesis, characterization, DNA binding and cleavage, and cytotoxicity","volume":"48","author":"Barve","year":"2009","journal-title":"Inorg. Chem."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jinorgbio.2012.12.020","article-title":"Interaction of vanadium(IV) with human serum apo-transferrin","volume":"121","author":"Mehtab","year":"2013","journal-title":"J. Inorg. Biochem."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1021\/acschembio.8b01100","article-title":"Transferrin Cycle and Clinical Roles of Citrate and Ascorbate in Improved Iron Metabolism","volume":"14","author":"Levina","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"S529","DOI":"10.1093\/cid\/ciz825","article-title":"The Role of Iron and Siderophores in Infection, and the Development of Siderophore Antibiotics","volume":"69","author":"Page","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.molmed.2016.10.005","article-title":"Siderophores in Iron Metabolism: From Mechanism to Therapy Potential","volume":"22","author":"Wilson","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_258","first-page":"91","article-title":"Blood glucose lowering and toxicological effects of zinc (II) complexes with maltol, threonine, and picolinic acid","volume":"112","author":"Kojima","year":"2002","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1093\/jac\/dkl350","article-title":"Deferiprone iron chelation as a novel therapy for experimental mucormycosis","volume":"58","author":"Ibrahim","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1080\/03630260701727093","article-title":"The Effects of Bicarbonate and its Combination with Chelating Agents Used for the Removal of Depleted Uranium in Rats","volume":"32","author":"Fukuda","year":"2008","journal-title":"Hemoglobin"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/03630260600642484","article-title":"Radiation Protection by Deferiprone in Animal Models","volume":"30","author":"Fukuda","year":"2006","journal-title":"Hemoglobin"},{"key":"ref_262","first-page":"173","article-title":"Interaction of L1, L1NAll and deferoxamine with gallium in vivo","volume":"28","author":"Eybl","year":"1992","journal-title":"Drugs Today"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1111\/bjh.17999","article-title":"The safety and acceptability of twice-daily deferiprone for transfusional iron overload: A multicentre, open-label, phase 2 study","volume":"197","author":"Badawy","year":"2022","journal-title":"Br. J. Haematol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4970\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:47:59Z","timestamp":1760122079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,4]]},"references-count":263,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054970"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054970","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,4]]}}}