Nicotinamide adenine dinucleotide (NAD) serves as a critical metabolite, functioning as a pivotal second messenger and a vital cofactor in various cellular processes essential for survival, including metabolism and maintaining genomic stability. Cellular NAD levels are maintained through multiple enzymatic pathways, with the NAMPT enzyme acting as a key regulator in the primary pathway responsible for sustaining these levels. Due to its regulatory role, NAMPT has become a focal point in drug discovery endeavors aiming to disrupt cancer metabolism.
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NAMPT inhibitors not only exhibit cytochrome inhibition but also produce harmful metabolites and have limited solubility in aqueous solutions. Nicotinamide phosphoribosyltransferase is notably expressed at higher levels in carcinomas, lymphomas, and astrocytomas compared to non-cancerous cells. Moreover, the activities of NAMPT inhibitors have demonstrated anti-cancer properties across various models of organ-specific cancers.