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.

Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells / 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. - In: PHILOSOPHICAL TRANSACTIONS - ROYAL SOCIETY. BIOLOGICAL SCIENCES. - ISSN 0962-8436. - 373:1748(2018), p. 20170150. [10.1098/rstb.2017.0150]

Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells

Mellini, Paolo;Marrocco, Biagina;Polletta, Lucia;Carnevale, Ilaria;Saladini, Serena;Stazi, Giulia;Zwergel, Clemens;Ferretti, Elisabetta;Tafani, Marco;Valente, Sergio;Mai, Antonello
2018

Abstract

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.
2018
Apoptosis; Autophagy; Enhancer of zeste homologue 2 inhibitors; Epigenetics; Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)
01 Pubblicazione su rivista::01a Articolo in rivista
Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells / 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. - In: PHILOSOPHICAL TRANSACTIONS - ROYAL SOCIETY. BIOLOGICAL SCIENCES. - ISSN 0962-8436. - 373:1748(2018), p. 20170150. [10.1098/rstb.2017.0150]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1147233
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