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Title

Small-molecule NOX inhibitors: ROS-generating NADPH oxidases as therapeutic targets

Authors
Clark, Robert A.
Lambeth, J David
Published in Antioxidants and Redox Signaling. 2009, vol. 11, no. 10, p. 2535-52
Abstract NOX NADPH oxidases are electron-transporting membrane enzymes whose primary function is the generation of reactive oxygen species (ROS). ROS produced by NOX enzymes show a variety of biologic functions, such as microbial killing, blood pressure regulation, and otoconia formation. Strong evidence suggests that NOX enzymes are major contributors to oxidative damage in pathologic conditions. Blocking the undesirable actions of NOX enzymes, therefore, is a therapeutic strategy for treating oxidative stress-related pathologies, such as ischemia/reperfusion tissue injury, and neurodegenerative and metabolic diseases. Most currently available NOX inhibitors have low selectivity, potency, and bioavailability, precluding a pharmacologic demonstration of NOX as therapeutic targets in vivo. This review has two main purposes. First, we describe a systematic approach that we believe should be followed in the search for truly selective NOX inhibitors. Second, we present a critical review of small-molecule NOX inhibitors described over the last two decades, including recently published patents from the pharmaceutical industry. Structures, activities, and in vitro/in vivo specificity of these NOX inhibitors are discussed. We conclude that NOX inhibition is a pertinent and promising novel pharmacologic concept, but that major efforts will be necessary to develop specific NOX inhibitors suited for clinical application.
Keywords Drug DesignDrug IndustryEnzyme Inhibitors/chemistry/metabolismHumansIsoenzymes/antagonists & inhibitors/metabolismMolecular StructureNADPH Oxidase/antagonists & inhibitors/metabolismProtein Subunits/metabolismReactive Oxygen Species/metabolismRespiratory Burst
Identifiers
PMID: 19309261
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Structures
Research groups Radicaux libres et cellules souches embryonnaires (60)
Groupe Schaller Karl-Lothard (neurochirurgie) (851)
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(ISO format)
JAQUET, Vincent et al. Small-molecule NOX inhibitors: ROS-generating NADPH oxidases as therapeutic targets. In: Antioxidants and Redox Signaling, 2009, vol. 11, n° 10, p. 2535-52. https://archive-ouverte.unige.ch/unige:5420

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Deposited on : 2010-03-16

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