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.
abstract: Iron mobilization from transferrin is one of the most important screening methods for the selection of chelators intended for clinical use in the treatment of iron overload in thalassemia and other conditions. In vitro and in vivo screening of approved and experimental chelating drugs has shown that only the alpha-ketohydroxypyridines deferiprone (L1) and 1-allyl-2 methyl-3-hydroxypyrid-4-one (L1NAll), are effective in the mobilization of iron from transferrin. Iron mobilization from transferrin and non-transferrin-bound-iron (NTBI) can be used to optimize existing chelation therapy protocols for the treatment of iron loaded patients. New chelation strategies involving L1 and its combination with deferoxamine (DFO) and other chelators can be used to increase iron excretion and reduce or prevent excess iron deposition in the heart and other vital organs of iron loaded patients by comparison to monotherapies. Deferiprone and its combinations may also have potential applications in the treatment of cancer, the anemia of chronic disease and other conditions.
authors.affiliation: Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus. pri_gjk@cylink.com.cy
authors.forename: George J
authors.initials: GJ
authors.lastname: Kontoghiorghes
mesh_terms: D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015913:Chelation Therapy; D002908:Chronic Disease; D003131:Combined Modality Therapy; D000077543:Deferiprone; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D008954:Models, Biological; D012157:Mononuclear Phagocyte System / Q000502:physiology; D009369:Neoplasms / Q000097:blood* / Q000150:complications; D011485:Protein Binding; D011728:Pyridones / Q000494:pharmacology* / Q000627:therapeutic use; D013789:Thalassemia / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D014168:Transferrin / Q000378:metabolism*; D065227:Transfusion Reaction
chemical_list: C507647:1-allyl-2-methyl-3-hydroxypyrid-4-one; D007502:Iron Chelating Agents; D011728:Pyridones; D014168:Transferrin; D000077543:Deferiprone; D007501:Iron