TY - JOUR
T1 - Identification of Novel Triazole-Based Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors Endowed with Antiproliferative and Antiinflammatory Activity
AU - Travelli, Cristina
AU - Aprile, Silvio
AU - Rahimian, Reza
AU - Grolla, Ambra A.
AU - Rogati, Federica
AU - Bertolotti, Mattia
AU - Malagnino, Floriana
AU - Di Paola, Rosanna
AU - Impellizzeri, Daniela
AU - Fusco, Roberta
AU - Mercalli, Valentina
AU - Massarotti, Alberto
AU - Stortini, Giorgio
AU - Terrazzino, Salvatore
AU - Del Grosso, Erika
AU - Fakhfouri, Gohar
AU - Troiani, Maria Pia
AU - Alisi, Maria Alessandra
AU - Grosa, Giorgio
AU - Sorba, Giovanni
AU - Canonico, Pier Luigi
AU - Orsomando, Giuseppe
AU - Cuzzocrea, Salvatore
AU - Genazzani, Armando A.
AU - Galli, Ubaldina
AU - Tron, Gian Cesare
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/3/9
Y1 - 2017/3/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85015063854&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.6b01392
DO - 10.1021/acs.jmedchem.6b01392
M3 - Article
SN - 0022-2623
VL - 60
SP - 1768
EP - 1792
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 5
ER -
