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Design, Synthesis and Biological Screening of NOX4 Inhibitors

Amol Kulkarni
Howard University
Chemistry Building, Room 400
Organic Seminar

NADPH oxidase (NOX) enzymes catalyze NADPH-dependent generation of reactive oxygen species and play a pivotal role in various physiological and pathological processes. Recent literature strongly suggests that NOX4 isoform plays a significant role in many disease states, such as fibrosis, cancers, and atherosclerosis. Thus, selective and potent inhibitors of NOX4 have the potential to be employed for the clinical management of a wide spectrum of disease states. Through a multi-institutional drug discovery collaboration, our pharmacophore modeling and computational chemistry studies led ultimately to the identification of novel sulfonylurea scaffold with promising NOX4-selective inhibition. The synthesis of the sulfonylurea compounds and their in vitro screening will be highlighted during the presentation. Application of our compounds in inflammation-associated disease states will also be presented.

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