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  • Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as therapeutics: rationales, controversies, clinical experience.

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

Current drug targets (2013-03-28)
Fabrizio Montecucco, Michele Cea, Inga Bauer, Debora Soncini, Irene Caffa, Denise Lasigliè, Aimable Nahimana, Antonio Uccelli, Santina Bruzzone, Alessio Nencioni
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Nicotinamide (Niacinamide), analytical standard
Supelco
Niacinamide, Pharmaceutical Secondary Standard; Certified Reference Material
Nicotinamide, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Niacinamide, meets USP testing specifications
Sigma-Aldrich
Nicotinamide, BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Nicotinamide, ≥98% (HPLC), powder
Supelco
Nicotinamide (Vitamin B3) solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
USP
Niacinamide, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Nicotinamide, ≥99.5% (HPLC)
Sigma-Aldrich
Nicotinamide, ≥98.5% (HPLC)