Small Molecule Regulators Targeting NAD+ Biosynthetic Enzymes

Nicotinamide adenine dinucleotide (NAD(+)) is a key player in many metabolic pathways as an activated carrier of electrons. In addition to being the cofactor for redox reactions, NAD(+) also serves as the substrate for various enzymatic transformations such as adenylation and ADP-ribosylation. Maintaining cellular NAD(+) homeostasis has been suggested as an effective anti-aging strategy. Given the importance of NAD(+) in regulating a broad spectrum of cellular events, small molecules targeting NAD+ metabolism have been pursued as therapeutic interventions for the treatment of mitochondrial disorders and age-related diseases. In this article, small molecule regulators of NAD(+) biosynthetic enzymes will be reviewed. The focus will be given to the discovery and development of these molecules, the mechanism of action as well as their therapeutic potentials.