DEVELOPMENT OF IRON CHELATORS TO TREAT IRON OVERLOAD DISEASE AND THEIR USE AS EXPERIMENTAL TOOLS TO PROBE INTRACELLULAR IRON-METABOLISM

The development of an orally effective iron (Fe) chelator for the trea tment of Fe overload diseases such as beta-thalassemia has been a diff icult challenge. Even though the drug in current clinical use, desferr ioxamine (DFO), is efficient and remarkably free of toxicity, it suffe rs from not being orally effective and requiring long subcutaneous inf usion to mobilize sufficient quantities of Fe. In addition, DFO is ver y expensive, which precludes it from treating most of the world's thal assemic population. Therefore, the development of an economical and or ally effective Fe chelator is of great importance. Despite the screeni ng of a wide range of structurally diverse ligands from both natural a nd synthetic sources, few compounds have been promising enough to proc eed to clinical trials. In the current review, the properties of an id eal chelator are discussed, followed by a description of the most succ essful ligands that have been identified. Apart from the use of Fe che lators as therapeutic agents, some of these compounds have also been u seful as experimental probes to investigate cellular Fe metabolism. We describe here the most important of these studies. (C) 1998 Wiley-Lis s, Inc.