Iron chelators as therapeutic iron depletion agents

The great promise of iron depletion as a therapeutic strategy for various diseases, including iron overload, cancers, Alzheimer’s disease, Parkinson’s disease, tuberculosis, HIV, and fungal and malaria infection, has stimulated research on the development of iron chelators as iron depletion agents. In November 2005, the FDA approved deferasirox (ICL670A; Exjade®), the first once-daily oral drug for treatment of chronic iron overload. So far, five iron chelators, deferoxamine, deferiprone, deferasirox, dexrazorane and ciclopirox, have been approved for use in iron overload, anticancer or antifungal therapy. Triapine® is in Phase I and II clinical trials for the treatment of various metastatic and solid cancers. A desferrithiocin analogue, deferitrin, is presently in a Phase I trial for the treatment of iron overload diseases. Among the iron chelators being evaluated in preclinical settings are the analogues of deferiprone, pyridoxal isonicotinoyl hydrazone, desferrithiocin, deferoxamine, thiosemicarbazone, tachpyridine, N,N′-bis(2-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid and hydroxyquinoline. This review describes the comparative properties of iron chelators in clinical use and evaluates the patent status of the novel synthetic iron chelators in preclinical settings.