HTS to Find Inhibitors of p47phox, a Regulatory Protein of Noxes

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DESCRIPTION (provided by applicant): Numerous diseases are linked to inflammation and oxidative stress. Nox enzymes provide the majority of reactive oxygen species associated with oxidative stress and have recently been validated as targets for drugs that would prevent and treat these conditions. Technical problems have to date prevented the adaptation of Nox activity assays for high throughput screening (HTS). In collaboration with Dr. Haian Fu, Director of Emory's MLSCN center, we have developed and optimized a novel HTS method with which we have successfully selected new candidate inhibitors of Noxes. Secondary activity screens that we developed and tested allowed us to identify bona fide Nox inhibitors that are candidates for lead drug compounds. Continuing our collaboration with Dr. Fu, we will use the HTS method to screen the MLSCN library at the Emory MLSCN center. Using hits from this screen, we will carry out secondary activity and counterscreens to determine the highest potency and most selective Nox1 and Nox2 inhibitors. Such inhibitors should provide valuable tools for research, and may serve as leads for drugs that can prevent and/or cure disease. Follow-on studies will focus on hit-to-lead development with the goal of identifying candidate drugs.