Inhibitors of the heme oxygenase - carbon monoxide system: on the doorstep of the clinic?

Kinobe, RT; Dercho, RA; Nakatsu, K

HERO ID

610534

Reference Type

Journal Article

Year

2008

PMID

18758507

HERO ID 610534
In Press No
Year 2008
Title Inhibitors of the heme oxygenase - carbon monoxide system: on the doorstep of the clinic?
Authors Kinobe, RT; Dercho, RA; Nakatsu, K
Journal Canadian Journal of Physiology and Pharmacology
Volume 86
Issue 9
Page Numbers 577-599
Abstract 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. Au cours de la dernière décennie, de nombreuses études ont contribué à enrichir notre compréhension de la physiologie, de la pathologie et de la pharmacologie des hèmes oxygénases (HO) ; on envisage d’ailleurs des traitements basés sur l’administration d’agonistes de l’HO et d’inhibiteurs de l’HO. Notre connaissance actuelle est basée principalement sur l’application judicieuse des métalloporphyrines, inhibiteurs de l’HO car elles posent des problèmes de sélectivité. Récemment, on a identifié des composés à base d’imidazole dotés d’un pouvoir plus sélectif concernant les inhibiteurs de l’HO. La prochaine génération d’inhibiteurs de l’HO pr&#xE9... [ABSTRACT FROM AUTHOR] Copyright of Canadian Journal of Physiology & Pharmacology is the property of NRC Research Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)
Doi 10.1139/Y08-066
Pmid 18758507
Wosid WOS:000259795500001
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science WOS:000259795500001
Is Public Yes
Keyword HEME oxygenase; CARBON monoxide; IMIDAZOLES; HYPERBILIRUBINEMIA; NERVOUS system -- Degeneration; MYCOSES; heme oxygenases; imidazole-based inhibitors and clinical applications; metalloporphyrins
Is Qa No