Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as therapeutics: Rationales, controversies, clinical experience

Fabrizio Montecucco, Michele Cea, Inga Bauer, Debora Soncini, Irene Caffa, Denise Lasigliè, Aimable Nahimana, Antonio Uccelli, Santina Bruzzone, Alessio Nencioni

Research output: Contribution to journalArticle

Abstract

Nicotinamide adenine dinucleotide (NAD+) biosynthesis from nicotinamide is used by mammalian cells to replenish their NAD+ stores and to avoid unwanted nicotinamide accumulation. Pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT), the key enzyme in this biosynthetic pathway, almost invariably leads to intracellular NAD+ depletion and, when protracted, to ATP shortage and cell demise. Cancer cells and activated immune cells express high levels of NAMPT and are highly susceptible to NAMPT inhibitors, as shown by the activity of these agents in models of malignant and inflammatory disorders. As the spectrum of conditions which could benefit from pharmacological NAMPT inhibition becomes broader, the mechanisms accounting for their activity are also eventually becoming apparent, including the induction of autophagy and the impairment of Ca2+- and NF-κB-dependent signaling. Here, we discuss the rationales for exploiting NAMPT inhibitors in cancer and inflammatory diseases and provide an overview of the preclinical and clinical studies in which these agents have been evaluated.

Original languageEnglish
Pages (from-to)637-643
Number of pages7
JournalCurrent Drug Targets
Volume14
Issue number6
DOIs
Publication statusPublished - 2013

Keywords

  • Angiogenesis
  • Cancer
  • Cardiovascular disorders
  • Chemotaxis
  • Inflammation
  • NAD+
  • NAMPT
  • Sirtuins

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Fingerprint Dive into the research topics of 'Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as therapeutics: Rationales, controversies, clinical experience'. Together they form a unique fingerprint.

  • Cite this

    Montecucco, F., Cea, M., Bauer, I., Soncini, D., Caffa, I., Lasigliè, D., Nahimana, A., Uccelli, A., Bruzzone, S., & Nencioni, A. (2013). Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as therapeutics: Rationales, controversies, clinical experience. Current Drug Targets, 14(6), 637-643. https://doi.org/10.2174/1389450111314060003