Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) in cancer: a patent review

Introduction: Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD) from nicotinamide. In addition to its role as essential redox cofactor, NAD also functions as a substrate for NAD-consuming enzymes, regulating multiple cellular processes such as DNA repair and gene expression, fundamental to sustain energetic needs for tumor growth. In this sense, NAMPT over-expression represents a common strategy that several tumor types adopt to sustain NAD production. In addition to its enzymatic role, NAMPT behaves as cytokine-like protein with pro-inflammatory function. Increasing evidence demonstrated that NAMPT inhibition represents a promising anti-cancer strategy to deplete NAD and impair cellular metabolism in cancer conditions. Areas covered: By using Espacenet, we collected the patents which identified new molecules, compounds, formulations and methods able to inhibit NAMPT from 2007 to date. Expert opinion: Most of the collected patents focused the attention on the ability of different compounds to inhibit the enzymatic activity of NAMPT, lacking other important aspects related to the extracellular role of NAMPT and the ability of alternative enzymes to counteract NAMPT-mediated NAD depletion. It is necessary to consider also these aspects to promote novel strategies and create novel inhibitors and molecules useful as anti-cancer compounds.