Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells
01 Pubblicazione su rivista
Mellini Paolo, Marrocco Biagina, Borovika Diana, Polletta Lucia, Carnevale Ilaria, Saladini Serena, Stazi Giulia, Zwergel Clemens, Trapencieris Peteris, Ferretti Elisabetta, Tafani Marco, Valente Sergio, Mai Antonello
ISSN: 0962-8436
Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihy-dropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.