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 treatment of Fe overload diseases such as beta-thalassemia has been a difficult challenge. Even though the drug in current clinical use, desferrioxamine (DFO), is efficient and remarkably free of toxicity, it suffers from not being orally effective and requiring long subcutaneous infusion to mobilize sufficient quantities of Fe. In addition, DFO is very expensive, which precludes it from treating most of the world's thalassemic population. Therefore, the development of an economical and orally effective Fe chelator is of great importance. Despite the screening of a wide range of structurally diverse ligands from both natural and synthetic sources, few compounds have been promising enough to proceed to clinical trials. In the current review, the properties of an ideal chelator are discussed, followed by a description of the most successful ligands that have been identified. Apart from the use of Fe chelators as therapeutic agents, some of these compounds have also been useful as experimental probes to investigate cellular Fe metabolism. We describe here the most important of these studies.