NAD+ is an essential cofactor for several cellular functions. In mammals, NAD+ can be synthesized from Nicotinamide, nicotinic acid or tryptophan, by nicotinamide phosphoribosyltransferase (Nampt). Nampt occupies a pivotal role in controlling the activity of several cellular enzymes. Importantly it is upreguated in solid tumors and hematologic malignancies, however roles of this enzyme in cancer are to date poorly understood. Published data have shown that the intracellular depletion of NAD+ has antitumor effect and the chemical NAMPT inhibitor FK866 is reported to induce tumor cell death.
Based on the reported effects of FK866, I will investigate the effect and the mechanism of action of this novel compound against Multiple Myeloma cells, in order to provide the basis for an innovative approach to this hematological malignance.