Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors as Therapeutics: Rationales, Controversies, Clinical Experience.

Détails

ID Serval
serval:BIB_2F6E83FE64FD
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors as Therapeutics: Rationales, Controversies, Clinical Experience.
Périodique
Current Drug Targets
Auteur⸱e⸱s
Montecucco F., Cea M., Bauer I., Soncini D., Caffa I., Lasigliè D., Nahimana A., Uccelli A., Bruzzone S., Nencioni A.
ISSN
1873-5592 (Electronic)
ISSN-L
1389-4501
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
14
Numéro
6
Pages
637-643
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
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 Ca(2+) - 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.
Pubmed
Web of science
Création de la notice
13/06/2013 16:53
Dernière modification de la notice
20/08/2019 13:13
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