Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells

…, G Giannaccini, A Lucacchini, N Funel…

Index: Granchi, Carlotta; Roy, Sarabindu; Giacomelli, Chiara; MacChia, Marco; Tuccinardi, Tiziano; Martinelli, Adriano; Lanza, Mario; Betti, Laura; Giannaccini, Gino; Lucacchini, Antonio; Funel, Nicola; Leon, Leticia G.; Giovannetti, Elisa; Peters, Godefridus J.; Palchaudhuri, Rahul; Calvaresi, Emilia C.; Hergenrother, Paul J.; Minutolo, Filippo Journal of Medicinal Chemistry, 2011 , vol. 54, # 6 p. 1599 - 1612

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Citation Number: 109

Abstract

Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from “normal” oxidative phosphorylation to increased glycolysis even under sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate dehydrogenase (LDH-A), is overexpressed by ...