Six Years (2012–2018) of Researches on Catalytic EZH2 Inhibitors: The Boom of the 2‐Pyridone Compounds

Discovery of EBI-2511: A Highly Potent and Orally Active EZH2 Inhibitor for the Treatment of Non-Hodgkin’s Lymphoma

(2018) Biao Lu et al.   ACS Medicinal Chemistry Letters

Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497)

(2017) Pei-Pei Kung et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy

(2017) Ying Huang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Guided Design of EED Binders Allosterically Inhibiting the Epigenetic Polycomb Repressive Complex 2 (PRC2) Methyltransferase

(2017) Andreas Lingel et al.   JOURNAL OF MEDICINAL CHEMISTRY

Dual inhibition of EZH1/2 breaks the quiescence of leukemia stem cells in acute myeloid leukemia

(2017) S Fujita et al.   LEUKEMIA

An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED

(2017) Wei Qi et al.   Nature Chemical Biology

The EED protein–protein interaction inhibitor A-395 inactivates the PRC2 complex

(2017) Yupeng He et al.   Nature Chemical Biology

The histone methyltransferase EZH2 as a druggable target in SHH medulloblastoma cancer stem cells

(2017) Evelina Miele et al.   Oncotarget

Discovery and Molecular Basis of a Diverse Set of Polycomb Repressive Complex 2 Inhibitors Recognition by EED

(2017) Ling Li et al.   PLoS One

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

(2016) Rishi G. Vaswani et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure–Activity Relationship Studies for Enhancer of Zeste Homologue 2 (EZH2) and Enhancer of Zeste Homologue 1 (EZH1) Inhibitors

(2016) Xiaobao Yang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design and Synthesis of Pyridone-Containing 3,4-Dihydroisoquinoline-1(2H)-ones as a Novel Class of Enhancer of Zeste Homolog 2 (EZH2) Inhibitors

(2016) Pei-Pei Kung et al.   JOURNAL OF MEDICINAL CHEMISTRY

An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation

(2016) George P Souroullas et al.   NATURE MEDICINE

Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance

(2016) Alexei Brooun et al.   Nature Communications

Small molecule epigenetic screen identifies novel EZH2 and HDAC inhibitors that target glioblastoma brain tumor-initiating cells

(2016) Natalie Grinshtein et al.   Oncotarget

ZLD1122, a novel EZH2 and EZH1 small molecular inhibitor, blocks H3K27 methylation and diffuse large B cell lymphoma cell growth

(2016) Tiantao Gao et al.   RSC Advances

Selective inhibition of EZH2 by ZLD1039 blocks H3K27methylation and leads to potent anti-tumor activity in breast cancer

(2016) Xuejiao Song et al.   Scientific Reports

Discovery, design, and synthesis of indole-based EZH2 inhibitors

(2015) Victor S. Gehling et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Polycomb genes, miRNA, and their deregulation in B-cell malignancies

(2015) G. G. Wang et al.   BLOOD

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

(2015) Ping Zhang et al.   INTERNATIONAL JOURNAL OF CANCER

EZH2 Inhibition Blocks Multiple Myeloma Cell Growth through Upregulation of Epithelial Tumor Suppressor Genes

(2015) H. Hernando et al.   MOLECULAR CANCER THERAPEUTICS

Development of secondary mutations in wild-type and mutant EZH2 alleles cooperates to confer resistance to EZH2 inhibitors

(2015) V Gibaja et al.   ONCOGENE

EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

(2015) John E. Campbell et al.   ACS Medicinal Chemistry Letters

Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors

(2015) Theresa Baker et al.   Oncotarget

Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia

(2014) B. Xu et al.   BLOOD

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

(2014) Roberta Ciarapica et al.   BMC CANCER

EZH2 Inhibitor Efficacy in Non-Hodgkin’s Lymphoma Does Not Require Suppression of H3K27 Monomethylation

(2014) William D. Bradley et al.   CHEMISTRY & BIOLOGY

An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1

(2013) Kyle D. Konze et al.   ACS Chemical Biology

EZH2 mutations are frequent and represent an early event in follicular lymphoma

(2013) C. Bodor et al.   BLOOD

EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation

(2013) Wendy Béguelin et al.   CANCER CELL

Identification of EZH2 and EZH1 Small Molecule Inhibitors with Selective Impact on Diffuse Large B Cell Lymphoma Cell Growth

(2013) Shivani Garapaty-Rao et al.   CHEMISTRY & BIOLOGY

Histone Methyltransferase Inhibitors: Novel Epigenetic Agents for Cancer Treatment

(2013) C. Zagni et al.   CURRENT MEDICINAL CHEMISTRY

The Polycomb group (PcG) protein EZH2 supports the survival of PAX3-FOXO1 alveolar rhabdomyosarcoma by repressing FBXO32 (Atrogin1/MAFbx)

(2013) R Ciarapica et al.   ONCOGENE

Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2

(2013) S. K. Knutson et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2

(2013) Lamia Abd Al Kader et al.   VIRCHOWS ARCHIV

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

(2012) Sergio Valente et al.   BIOCHIMIE

EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations

(2012) Michael T. McCabe et al.   NATURE

A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells

(2012) Sarah K Knutson et al.   Nature Chemical Biology

Epigenetic protein families: a new frontier for drug discovery

(2012) Cheryl H. Arrowsmith et al.   NATURE REVIEWS DRUG DISCOVERY

Polycomb repressive complex 2 is required for MLL-AF9 leukemia

(2012) T. Neff et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation

(2012) W. Qi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2

(2012) Sharad K. Verma et al.   ACS Medicinal Chemistry Letters

Regulation of chromatin by histone modifications

(2011) Andrew J Bannister et al.   CELL RESEARCH

Novel 3,5-Bis(bromohydroxybenzylidene)piperidin-4-ones as Coactivator-Associated Arginine Methyltransferase 1 Inhibitors: Enzyme Selectivity and Cellular Activity

(2011) Donghang Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis

(2010) I. Velichutina et al.   BLOOD

Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation

(2010) D. B. Yap et al.   BLOOD

TNF/p38α/Polycomb Signaling to Pax7 Locus in Satellite Cells Links Inflammation to the Epigenetic Control of Muscle Regeneration

(2010) Daniela Palacios et al.   Cell Stem Cell

Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin

(2010) Ryan D Morin et al.   NATURE GENETICS

Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas

(2010) C. J. Sneeringer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Condensed DNA: Condensing the concepts

(2010) Vladimir B. Teif et al.   PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY

Protein methyltransferases as a target class for drug discovery

(2009) Robert A. Copeland et al.   NATURE REVIEWS DRUG DISCOVERY

Epigenetic Multiple Ligands: Mixed Histone/Protein Methyltransferase, Acetyltransferase, and Class III Deacetylase (Sirtuin) Inhibitors

(2008) Antonello Mai et al.   JOURNAL OF MEDICINAL CHEMISTRY

Ezh1 and Ezh2 Maintain Repressive Chromatin through Different Mechanisms

(2008) Raphael Margueron et al.   MOLECULAR CELL