Details

Autor(en) / Beteiligte

• Travelli, Cristina
• Aprile, Silvio
• Rahimian, Reza
• Grolla, Ambra A
• Rogati, Federica
• Bertolotti, Mattia
• Malagnino, Floriana
• di Paola, Rosanna
• Impellizzeri, Daniela
• Fusco, Roberta
• Mercalli, Valentina
• Massarotti, Alberto
• Stortini, Giorgio
• Terrazzino, Salvatore
• Del Grosso, Erika
• Fakhfouri, Gohar
• Troiani, Maria Pia
• Alisi, Maria Alessandra
• Grosa, Giorgio
• Sorba, Giovanni
• Canonico, Pier Luigi
• Orsomando, Giuseppe
• Cuzzocrea, Salvatore
• Genazzani, Armando A
• Galli, Ubaldina
• Tron, Gian Cesare

Titel

Identification of Novel Triazole-Based Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors Endowed with Antiproliferative and Antiinflammatory Activity

Ist Teil von

• Journal of medicinal chemistry, 2017-03, Vol.60 (5), p.1768-1792

Ort / Verlag

United States

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.