| Literature DB >> 28165742 |
Cristina Travelli1, Silvio Aprile1, Reza Rahimian2,3, Ambra A Grolla1, Federica Rogati1, Mattia Bertolotti1, Floriana Malagnino1, Rosanna di Paola4, Daniela Impellizzeri4, Roberta Fusco4, Valentina Mercalli1, Alberto Massarotti1, Giorgio Stortini5, Salvatore Terrazzino1, Erika Del Grosso1, Gohar Fakhfouri2, Maria Pia Troiani6, Maria Alessandra Alisi6, Giorgio Grosa1, Giovanni Sorba1, Pier Luigi Canonico1, Giuseppe Orsomando7, Salvatore Cuzzocrea4, Armando A Genazzani1, Ubaldina Galli1, Gian Cesare Tron1.
Abstract
Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme involved in the recycling of nicotinamide to maintain adequate NAD levels inside the cells. It has been postulated to be a pharmacological target, as it is overexpressed in cancer cells as well as in inflammatory diseases. We describe the synthesis and characterization of a novel class of one-digit nanomolar NAMPT inhibitors based on in vitro characterization. The most active compound tested, 30c, displayed activity in xenograft and allograft models, strengthening the potential of NAMPT inhibitors as antitumoral drugs. Furthermore, in the present contribution we describe the ability of 30c to significantly improve the outcome of colitis in mice. Given that this is the first report of an effect of NAMPT inhibitors in colitis, this result paves the way for novel applications for this class of compounds.Entities:
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Year: 2017 PMID： 28165742 DOI： 10.1021/acs.jmedchem.6b01392
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446