Document Detail


Sly as a Nox: The challenges, triumphs and pitfalls of selective NADPH Oxidase inhibition.
MedLine Citation:
PMID:  24070014     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Significance: Numerous studies in animal models and human subjects corroborate that elevated levels of reactive oxygen species (ROS) play a pivotal role in the progression of multiple diseases. As a major source of ROS in many organ systems, the NADPH oxidase (Nox) has become a prime target for therapeutic development. Recent Advances: In recent years, intense efforts have been dedicated to the development of pan- as well as isoform-specific Nox inhibitors as opposed to antioxidants that proved ineffective in clinical trials. Over the past decade, an array of compounds has been proposed in an attempt to fill this void. Critical Issues: Although many of these compounds have proven effective as Nox enzyme family inhibitors, isoform-specificity has posed a formidable challenge to the scientific community. This review surveys the most prominent Nox inhibitors, and discusses potential isoform-specificity, known mechanisms of action, as well as shortcomings. Some of these inhibitors hold substantial promise as targeted therapeutics. Future directions: Increased insight into the mechanisms of action and regulation of this family of enzymes as well as atomic structures of key Nox subunits are expected to give way to a broader spectrum of more potent, efficacious, and specific molecules. These lead molecules will assuredly serve as a basis for drug development aimed at treating a wide array of diseases associated with increased Nox activity.
Authors:
Eugenia Cifuentes-Pagano; Daniel N Meijles; Patrick J Pagano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-9-26
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-9-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Pittsburgh, Vascular Medicine Institute and Department of Pharmacology & Chemical Biology, Pittsburgh, Pennsylvania, United States ; mec110@pitt.edu.
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