Inhibitors of the heme oxygenase-carbon monoxide system: on the doorstep of the clinic?
Kinobe, Robert T., Dercho, Ryan A., and Nakatsu, Kanji (2008) Inhibitors of the heme oxygenase-carbon monoxide system: on the doorstep of the clinic? Canadian Journal of Physiology and Pharmacology, 86 (9). pp. 577-599.
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The past decade has seen substantial developments in our understanding of the physiology, pathology, and pharmacology of heme oxygenases (HO), to the point that investigators in the field are beginning to contemplate therapies based on administration of HO agonists or HO inhibitors. A significant amount of our current knowledge is based on the judicious application of metalloporphyrin inhibitors of HO, despite their limitations of selectivity. Recently, imidazole-based compounds have been identified as potent and more selective HO inhibitors. This ‘next generation’ of HO inhibitors offers a number of desirable characteristics, including isozyme selectivity, negligible effects on HO protein expression, and physicochemical properties favourable for in vivo distribution. Some of the applications of HO inhibitors that have been suggested are treatment of hyperbilirubinemia, neurodegenerative disorders, certain types of cancer, and bacterial and fungal infections. In this review, we address various approaches to altering HO activity with a focus on the potential applications of second-generation inhibitors of HO.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||heme oxygenases; metalloporphyrines; imidazole-based inhibitors; clinical applications|
|Date Deposited:||14 Jan 2010 04:56|
|FoR Codes:||06 BIOLOGICAL SCIENCES > 0606 Physiology > 060601 Animal Physiology - Biophysics @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110199 Medical Biochemistry and Metabolomics not elsewhere classified @ 50%
|SEO Codes:||92 HEALTH > 9202 Health and Support Services > 920201 Allied Health Therapies (excl. Mental Health Services) @ 100%|
|Citation Count from Web of Science||