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PCTH: a novel orally active chelator for the treatment of iron overload disease.
- Source :
-
Hemoglobin [Hemoglobin] 2006; Vol. 30 (1), pp. 93-104. - Publication Year :
- 2006
-
Abstract
- Our laboratories have prepared a novel class of iron (Fe) chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) class. This article will review the iron chelation efficacy of this series of chelators, both in cell culture and in animal models. Several PCIH analogs were shown to be effective at inducing iron mobilization and preventing iron uptake from the iron-transport protein, transferrin. Moreover, several of these ligands were effective at permeating the mitochondrion and inducing iron release. Studies in mice demonstrated that the PCIH analog, PCTH, was orally active and well tolerated by mice at doses ranging from 50 to 100 mg kg(-1), twice daily (b.d.). A dose-dependent increase in fecal 59Fe excretion was observed in the PCTH-treated group. This level of iron excretion was similar to that found for the orally effective chelators, pyridoxal isonicotinoyl hydrazone (PIH) and deferiprone (L1). The PCIH group of ligands clearly has the potential for the treatment of beta-thalassemia (thal) and Friedreich's Ataxia (FA).
- Subjects :
- Administration, Oral
Animals
Crystallography, X-Ray
Humans
Hydrazones administration & dosage
Hydrazones classification
Iron Chelating Agents administration & dosage
Iron Chelating Agents classification
Models, Molecular
Molecular Structure
Pyridines administration & dosage
Pyridines classification
Hydrazones therapeutic use
Iron Chelating Agents therapeutic use
Iron Overload drug therapy
Pyridines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0363-0269
- Volume :
- 30
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Hemoglobin
- Publication Type :
- Academic Journal
- Accession number :
- 16540421
- Full Text :
- https://doi.org/10.1080/03630260500455367