Literature DB >> 29685965

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

Paolo Mellini1, Biagina Marrocco1, Diana Borovika2, Lucia Polletta3, Ilaria Carnevale3, Serena Saladini3, Giulia Stazi1, Clemens Zwergel1, Peteris Trapencieris2, Elisabetta Ferretti3, Marco Tafani4, Sergio Valente5, Antonello Mai6,7.   

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-dihydropyridin-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.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.
© 2018 The Author(s).

Entities:  

Keywords:  apoptosis; autophagy; enhancer of zeste homologue 2 inhibitors; epigenetics

Mesh：

Substances：

Year:  2018        PMID： 29685965      PMCID： PMC5915724          DOI： 10.1098/rstb.2017.0150

Source DB:  PubMed          Journal:  Philos Trans R Soc Lond B Biol Sci        ISSN： 0962-8436            Impact factor:   6.237


  39 in total

1.  Synthesis and biological validation of novel synthetic histone/protein methyltransferase inhibitors.

Authors:  Antonello Mai; Sergio Valente; Donghang Cheng; Andrea Perrone; Rino Ragno; Silvia Simeoni; Gianluca Sbardella; Gerald Brosch; Angela Nebbioso; Mariarosaria Conte; Lucia Altucci; Mark T Bedford
Journal:  ChemMedChem       Date:  2007-07       Impact factor: 3.466

2.  Identification of PR-SET7 and EZH2 selective inhibitors inducing cell death in human leukemia U937 cells.

Authors:  Sergio Valente; Ilaria Lepore; Carmela Dell'Aversana; Maria Tardugno; Sabrina Castellano; Gianluca Sbardella; Stefano Tomassi; Salvatore Di Maro; Ettore Novellino; Roberto Di Santo; Roberta Costi; Lucia Altucci; Antonello Mai
Journal:  Biochimie       Date:  2012-06-16       Impact factor: 4.079

3.  ABCB1 and ABCG2 restrict the brain penetration of a panel of novel EZH2-Inhibitors.

Authors:  Ping Zhang; Mark C de Gooijer; Levi C M Buil; Jos H Beijnen; Gang Li; Olaf van Tellingen
Journal:  Int J Cancer       Date:  2015-04-24       Impact factor: 7.396

4.  An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1.

Authors:  Kyle D Konze; Anqi Ma; Fengling Li; Dalia Barsyte-Lovejoy; Trevor Parton; Christopher J Macnevin; Feng Liu; Cen Gao; Xi-Ping Huang; Ekaterina Kuznetsova; Marie Rougie; Alice Jiang; Samantha G Pattenden; Jacqueline L Norris; Lindsey I James; Bryan L Roth; Peter J Brown; Stephen V Frye; Cheryl H Arrowsmith; Klaus M Hahn; Gang Greg Wang; Masoud Vedadi; Jian Jin
Journal:  ACS Chem Biol       Date:  2013-04-24       Impact factor: 5.100

5.  Pharmacological inhibition of EZH2 as a promising differentiation therapy in embryonal RMS.

Authors:  Roberta Ciarapica; Elena Carcarino; Laura Adesso; Maria De Salvo; Giorgia Bracaglia; Pier Paolo Leoncini; Alessandra Dall'agnese; Federica Verginelli; Giuseppe M Milano; Renata Boldrini; Alessandro Inserra; Stefano Stifani; Isabella Screpanti; Victor E Marquez; Sergio Valente; Antonello Mai; Pier Lorenzo Puri; Franco Locatelli; Daniela Palacios; Rossella Rota
Journal:  BMC Cancer       Date:  2014-02-27       Impact factor: 4.430

6.  The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat.

Authors:  Kevin W Kuntz; John E Campbell; Heike Keilhack; Roy M Pollock; Sarah K Knutson; Margaret Porter-Scott; Victoria M Richon; Chris J Sneeringer; Tim J Wigle; Christina J Allain; Christina R Majer; Mikel P Moyer; Robert A Copeland; Richard Chesworth
Journal:  J Med Chem       Date:  2016-01-27       Impact factor: 7.446

Review 7.  Targeting EZH2 in cancer.

Authors:  Kimberly H Kim; Charles W M Roberts
Journal:  Nat Med       Date:  2016-02       Impact factor: 53.440

8.  TNF/p38α/polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration.

Authors:  Daniela Palacios; Chiara Mozzetta; Silvia Consalvi; Giuseppina Caretti; Valentina Saccone; Valentina Proserpio; Victor E Marquez; Sergio Valente; Antonello Mai; Sonia V Forcales; Vittorio Sartorelli; Pier Lorenzo Puri
Journal:  Cell Stem Cell       Date:  2010-10-08       Impact factor: 24.633

9.  Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell Lymphomas.

Authors:  Rishi G Vaswani; Victor S Gehling; Les A Dakin; Andrew S Cook; Christopher G Nasveschuk; Martin Duplessis; Priyadarshini Iyer; Srividya Balasubramanian; Feng Zhao; Andrew C Good; Robert Campbell; Christina Lee; Nico Cantone; Richard T Cummings; Emmanuel Normant; Steven F Bellon; Brian K Albrecht; Jean-Christophe Harmange; Patrick Trojer; James E Audia; Ying Zhang; Neil Justin; Shuyang Chen; Jon R Wilson; Steven J Gamblin
Journal:  J Med Chem       Date:  2016-10-28       Impact factor: 7.446

10.  AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2.

Authors:  Hana Kim; Keunsoo Kang; Joomyeong Kim
Journal:  Nucleic Acids Res       Date:  2009-03-17       Impact factor: 16.971
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  7 in total

1.  Epigenetics: the first 25 centuries.

Authors:  A Ganesan
Journal:  Philos Trans R Soc Lond B Biol Sci       Date:  2018-06-05       Impact factor: 6.237

2.  The R882H substitution in the human de novo DNA methyltransferase DNMT3A disrupts allosteric regulation by the tumor supressor p53.

Authors:  Jonathan E Sandoval; Norbert O Reich
Journal:  J Biol Chem       Date:  2019-10-22       Impact factor: 5.157

3.  Design of First-in-Class Dual EZH2/HDAC Inhibitor: Biochemical Activity and Biological Evaluation in Cancer Cells.

Authors:  Annalisa Romanelli; Giulia Stazi; Rossella Fioravanti; Clemens Zwergel; Elisabetta Di Bello; Silvia Pomella; Clara Perrone; Cecilia Battistelli; Raffaele Strippoli; Marco Tripodi; Donatella Del Bufalo; Rossella Rota; Daniela Trisciuoglio; Antonello Mai; Sergio Valente
Journal:  ACS Med Chem Lett       Date:  2020-03-19       Impact factor: 4.345

Review 4.  Six Years (2012-2018) of Researches on Catalytic EZH2 Inhibitors: The Boom of the 2-Pyridone Compounds.

Authors:  Rossella Fioravanti; Giulia Stazi; Clemens Zwergel; Sergio Valente; Antonello Mai
Journal:  Chem Rec       Date:  2018-10-19       Impact factor: 6.771

5.  A Novel Synthetic Compound (E)-5-((4-oxo-4H-chromen-3-yl)methyleneamino)-1-phenyl-1H-pyrazole-4-carbonitrile Inhibits TNFα-Induced MMP9 Expression via EGR-1 Downregulation in MDA-MB-231 Human Breast Cancer Cells.

Authors:  Munki Jeong; Euitaek Jung; Young Han Lee; Jeong Kon Seo; Seunghyun Ahn; Dongsoo Koh; Yoongho Lim; Soon Young Shin
Journal:  Int J Mol Sci       Date:  2020-07-18       Impact factor: 5.923

6.  Dissecting the role of novel EZH2 inhibitors in primary glioblastoma cell cultures: effects on proliferation, epithelial-mesenchymal transition, migration, and on the pro-inflammatory phenotype.

Authors:  Giulia Stazi; Ludovica Taglieri; Alice Nicolai; Annalisa Romanelli; Rossella Fioravanti; Stefania Morrone; Manuela Sabatino; Rino Ragno; Samanta Taurone; Marcella Nebbioso; Raffaella Carletti; Marco Artico; Sergio Valente; Susanna Scarpa; Antonello Mai
Journal:  Clin Epigenetics       Date:  2019-12-02       Impact factor: 6.551

Review 7.  Epigenetic Control of Autophagy in Cancer Cells: A Key Process for Cancer-Related Phenotypes.

Authors:  Paul Peixoto; Céline Grandvallet; Jean-Paul Feugeas; Michaël Guittaut; Eric Hervouet
Journal:  Cells       Date:  2019-12-17       Impact factor: 6.600
  7 in total

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