Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells
| Autor: | Diana Borovika, Ilaria Carnevale, Giulia Stazi, Lucia Polletta, Peteris Trapencieris, Sergio Valente, Clemens Zwergel, Serena Saladini, Antonello Mai, Elisabetta Ferretti, Paolo Mellini, Biagina Marrocco, Marco Tafani |
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| Rok vydání: | 2018 |
| Předmět: |
Genetics and Molecular Biology (all)
0301 basic medicine Methyltransferase Apoptosis Autophagy Enhancer of zeste homologue 2 inhibitors Epigenetics Biochemistry Genetics and Molecular Biology (all) Agricultural and Biological Sciences (all) Chemical biology Pyrazole Biochemistry General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Chemistry Cell growth EZH2 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Cancer research General Agricultural and Biological Sciences |
| Zdroj: | Philosophical Transactions of the Royal Society B: Biological Sciences. 373:20170150 |
| ISSN: | 1471-2970 0962-8436 |
| DOI: | 10.1098/rstb.2017.0150 |
| Popis: | 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-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1 H -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. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’. |
| Databáze: | OpenAIRE |
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