Pharmacophore-Based QSAR Model of Multi Scaffolds as NAMPT Inhibitors & Scaffold Diversity Analysis

NAD+ plays crucial roles in various biological processe and its aberrant regulation has been suggested to be critical in the pathogenesis of diverse diseases. Intracellular NAD+ is synthesized largely from nicotinamide mononucleotide (NMN), which is the product of reaction catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). Thus, the development of specific inhibitors targeting NAMPT has been suggested as a promising treatment strategy. In this study, we developed a pharmacophore-based QSAR model to discover novel NAMPT inhibitors based on diverse structural features. By virtual screening using the conformation model, we could identify eight novel active analogs having distinct pharmacophores. The biological activity of these candidates on cell viability were further examined. Our study proves the efficiency of our novel screening model and demonstrates its usefulness in the application of drug discovery process.