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ABSTRACT
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.
Article highlights
NAMPT, both in its intracellular and extracellular forms, exerts an important role in tumor cells.
Different patents identified new molecules, compounds, formulations and methods able to inhibit NAMPT activity.
The role of extracellular NAMPT as cytokine must be deeply investigated.
The enzyme NAPRT is an important NAMPT counterpart in NAD metabolism.
Dual-inhibitors, antibodies and the use of innovative technology could represent efficient tools to counteract NAMPT-dependent cancer conditions.
Abbreviations
| eNAMPT | = | extracellular NAMPT |
| IC50 | = | half-maximal inhibitory concentrations |
| iNAMPT | = | intracellular NAMPT |
| NA | = | nicotinic acid |
| NADS | = | NAD synthetase |
| NAM | = | nicotinamide |
| NAMN | = | nicotinic acid mononucleotide |
| NAMPT | = | nicotinamide phosphoribosyltransferase |
| NAMPTi | = | NAMPT inhibitor |
| NAPRT | = | nicotinate phosphoribosyltransferase |
| NMN | = | nicotinamide mononucleotide |
| NMNAT | = | nicotinamide mononucleotide adenyltransferase |
| NR | = | nicotinamide riboside |
| NRK | = | nicotinamide riboside kinase |
| PARPs | = | poly-ADP-ribosyl polymerases |
| PROTAC | = | PROteolysis TArgeting Chimeras |
| PRPP | = | 5-phosphoribosyl-1-pyrophosphate |
| QA | = | quinolinic acid |
| QPRT | = | quinolinate phosphoribosyltransferase |
| TR-FRET | = | Time-Resolved Fluorescence Resonance Energy Transfer |
| TLR4 | = | toll-like receptor 4 |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.