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Published on: February 24, 2018
The NADPH Oxidase Family and Its Inhibitors
Mathieu Chocry1, Ludovic Leloup1
1Aix-Marseille Université, Institut de Neurophysiopathologie (INP), CNRS, Marseille, France.
Abstract:
The oxidative stress, resulting from an imbalance in the production and scavenging of reactive oxygen species (ROS), is known to be involved in the development and progression of several pathologies. The excess of ROS production is often due to an overactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) and for this reason these enzymes became promising therapeutic targets. However, even if NOX are now well characterized, the development of new therapies is limited by the lack of highly isoform-specific inhibitors. In the past decade, several groups and laboratories have screened thousands of molecules to identify new specific inhibitors with low off-target effects. These works have led to the characterization of several new potent NOX inhibitors; however, their specificity varies a lot depending on the molecules. Here, we are reviewing more than 25 known NOX inhibitors, focusing mainly on the newly identified ones such as APX-115, NOS31, Phox-I1 and 2, GLX7013114, and GSK2795039. To have a better overall view of these molecules, the inhibitors were classified according to their specificity, from pan-NOX inhibitors to highly isoform-specific ones. We are also presenting the use of these compounds both in vitro and in vivo. Several of these new molecules are potent and very specific inhibitors that could be good candidates for the development of new drugs. Even if the results are very promising, most of these compounds were only validated in vitro or in mice models and further investigations will be required before using them as potential therapies.
Insights
New nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) inhibitors show promise for treating diseases linked to oxidative stress. Researchers reviewed over 25 inhibitors, classifying them by specificity and evaluating their therapeutic potential.
Area of Science:
- Biochemistry
- Pharmacology
- Molecular Biology
Background:
- Oxidative stress, caused by reactive oxygen species (ROS) imbalance, contributes to various pathologies.
- Overactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) is a key source of excess ROS.
- Developing effective therapies is hindered by a lack of highly isoform-specific NOX inhibitors.
Purpose of the Study:
- To review and classify over 25 known NOX inhibitors, with a focus on newly identified compounds.
- To assess the specificity and therapeutic potential of these inhibitors for treating oxidative stress-related conditions.
- To summarize the in vitro and in vivo applications of these NOX inhibitors.
Main Methods:
- Literature review of NOX inhibitors, including recent compounds like APX-115, NOS31, Phox-I1 and 2, GLX7013114, and GSK2795039.
- Classification of inhibitors based on their specificity, ranging from pan-NOX to isoform-specific.
- Analysis of in vitro and in vivo data for evaluated compounds.
Main Results:
- Several newly identified NOX inhibitors demonstrate high potency and specificity.
- Inhibitors were categorized by their specificity profiles, offering a clear overview of available agents.
- Compounds like APX-115, NOS31, Phox-I1 and 2, GLX7013114, and GSK2795039 are highlighted for their potential.
Conclusions:
- Newly developed NOX inhibitors are potent and specific, presenting promising candidates for new drug development.
- While promising, most compounds require further investigation beyond in vitro and mouse models for clinical application.
- Targeting NOX enzymes offers a viable therapeutic strategy for diseases associated with oxidative stress.
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