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Updated: Sep 18, 2025

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
Published on: February 24, 2018
Enhancing Selectivity and Potency of SNAr Covalent Inhibitors of NADPH Oxidase Enzymes
Blessing C Ogboo1, Kishan B Patel1, Marta Massari2
1Department of Chemistry, College of Arts and Sciences, The State University of New York at Buffalo, Buffalo, New York 14260, United States.
Abstract:
Dysregulated reactive oxygen species (ROS) are implicated in various diseases, positioning NADPH oxidase enzymes (NOXs) as attractive therapeutic targets. However, progress in tool compound discovery has been hindered by rational optimization strategies that can improve isoform selectivity. Starting from a nonselective but well-behaved NOX inhibitor (VAS2870), we have discovered a first-in-class NOX5 selective inhibitor through minor functionalization on a benzoxazolethiol moiety, which is released upon covalent modification to the target enzyme. These unexpected findings showcase a unique strategy for optimizing SNAr covalent inhibitors and offer new avenues for the development of isoform-selective NOX inhibitors.
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