Iron chelator research: past, present, and future.
The occurrence of in vivo iron toxicity in the human body can be categorized into iron overload and non-iron overload conditions. Iron overload conditions are common in beta-thalassemia and hereditary hemochromatosis patients, and anthracycline mediated cardiotoxicity is an example of a non-iron overload condition in cancer patients, in which the toxicity is iron-dependent. While hundreds of iron chelators have been evaluated in animal studies, only a few have been studied in humans. Examples of iron chelator drugs are desferrioxamine (DFO), deferiprone (L1), and dexrazoxane (ICRF 187). The compound ICL670 has completed phase II clinical trials and a phase III trial is planned in 2003. Triapine is currently in phase II clinical trial as an anticancer agent. CP502, GT56-252, NaHBED, and MPB0201 are examples of new chelators in preclinical/clinical development. In the past decade, many new viable utilities for iron chelators have been reported. This includes the use of iron chelators as antiviral, photoprotective, antiproliferative, and antifibrotic agents. This review will focus on the status of drug development for the treatment of iron overload in patients with beta-thalassemia and the potential use of iron chelators in the prevention and treatment of other diseases.
Tam
Tim F
TF
Medicinal Chemistry Department, Apotex Research, Inc., 400 Ormont Drive, Toronto, Ontario, Canada. ttam@apotex.com
Leung-Toung
Regis
R
Li
Wanren
W
Wang
Yingsheng
Y
Karimian
Khashayar
K
Spino
Michael
M
D000818:Animals; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species
D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D007501:Iron