EZH2 inhibitors: a patent review (2014-2016)

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

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

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

(2017) Ling Li et al.   PLoS One

EZH2 promotes invasion and metastasis of laryngeal squamous cells carcinoma via epithelial-mesenchymal transition through H3K27me3

(2016) HuaNan Luo et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

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

Targeting EZH2 in cancer

(2016) Kimberly H Kim 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

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

(2016) H. Zhang et al.   Cancer Discovery

Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy

(2016) Ludovica Morera et al.   Clinical Epigenetics

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

(2016) Angel R. de Lera et al.   Clinical Epigenetics

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

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

Preclinical pharmacokinetic studies of 3-deazaneplanocin A, a potent epigenetic anticancer agent, and its human pharmacokinetic prediction using GastroPlus™

(2015) Feng Sun et al.   EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Epigenetic-based therapy: From single- to multi-target approaches

(2015) Rosaria Benedetti et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

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

Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent cancer

(2015) Huiming Chen et al.   Oncotarget

Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer

(2015) Jason S. Kirk et al.   Oncotarget

Myc Enforces Overexpression of EZH2 in Early Prostatic Neoplasia via Transcriptional and Post-transcriptional Mechanisms

(2015) Cheryl M. Koh 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

Astemizole Arrests the Proliferation of Cancer Cells by Disrupting the EZH2-EED Interaction of Polycomb Repressive Complex 2

(2014) Xiangqian Kong et al.   JOURNAL OF MEDICINAL CHEMISTRY

PRC2 loss amplifies Ras signaling in cancer

(2014) Annika Baude et al.   NATURE GENETICS

Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas

(2014) Sarah K. Knutson et al.   PLoS One

Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2

(2014) Christopher G. Nasveschuk et al.   ACS Medicinal Chemistry Letters

Distinct and separable roles for EZH2 in neurogenic astroglia

(2014) William W Hwang et al.   eLife

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

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

Physical Interaction between MYCN Oncogene and Polycomb Repressive Complex 2 (PRC2) in Neuroblastoma

(2013) Daisy Corvetta et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Combined modulation of polycomb and trithorax genes rejuvenates β cell replication

(2013) Josie X. Zhou et al.   JOURNAL OF CLINICAL INVESTIGATION

Targeted disruption of the EZH2–EED complex inhibits EZH2-dependent cancer

(2013) Woojin Kim et al.   Nature Chemical Biology

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

Non-coding RNAs and EZH2 interactions in cancer: Long and short tales from the transcriptome

(2012) Leonidas Benetatos et al.   INTERNATIONAL JOURNAL OF CANCER

Twist-1 Induces Ezh2 Recruitment Regulating Histone Methylation along the Ink4A/Arf Locus in Mesenchymal Stem Cells

(2012) D. Cakouros et al.   MOLECULAR AND CELLULAR BIOLOGY

Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27)

(2012) M. T. McCabe 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

Ectopic expression of the histone methyltransferase Ezh2 in haematopoietic stem cells causes myeloproliferative disease

(2012) A. Herrera-Merchan et al.   Nature Communications

FOXC1, a target of polycomb, inhibits metastasis of breast cancer cells

(2011) Juan Du et al.   BREAST CANCER RESEARCH AND TREATMENT

The role of EZH2 in tumour progression

(2011) C-J Chang et al.   BRITISH JOURNAL OF CANCER

Exploiting Cancer Cell Vulnerabilities to Develop a Combination Therapy for Ras-Driven Tumors

(2011) Thomas De Raedt et al.   CANCER CELL

EZH2 Promotes Expansion of Breast Tumor Initiating Cells through Activation of RAF1-β-Catenin Signaling

(2011) Chun-Ju Chang et al.   CANCER CELL

Phosphoryl-EZH-ion

(2011) Giuseppina Caretti et al.   Cell Stem Cell

Aberrations of EZH2 in Cancer

(2011) A. Chase et al.   CLINICAL CANCER RESEARCH

Myocyte Enhancer Factor-2 Interacting Transcriptional Repressor (MITR) Is a Switch That Promotes Osteogenesis and Inhibits Adipogenesis of Mesenchymal Stem Cells by Inactivating Peroxisome Proliferator-activated Receptor γ-2

(2011) Ya-Huey Chen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Myc Regulates the Transcription of the PRC2 Gene To Control the Expression of Developmental Genes in Embryonic Stem Cells

(2011) F. Neri et al.   MOLECULAR AND CELLULAR BIOLOGY

The Polycomb complex PRC2 and its mark in life

(2011) Raphaël Margueron et al.   NATURE

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

Polycomb Group Proteins: Multi-Faceted Regulators of Somatic Stem Cells and Cancer

(2010) Martin Sauvageau et al.   Cell Stem Cell

Epigenetic factors in cancer development: Polycomb group proteins

(2010) Andrea Piunti et al.   Future Oncology

CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells

(2010) Yongkun Wei et al.   NATURE CELL BIOLOGY

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

TNF Inhibits Notch-1 in Skeletal Muscle Cells by Ezh2 and DNA Methylation Mediated Repression: Implications in Duchenne Muscular Dystrophy

(2010) Swarnali Acharyya et al.   PLoS One

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

Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex

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

Histone H3K27 methyltransferase Ezh2 represses Wnt genes to facilitate adipogenesis

(2010) L. Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells

(2009) Elena Ezhkova et al.   CELL

Recruitment of Polycomb group complexes and their role in the dynamic regulation of cell fate choice

(2009) B. Schuettengruber et al.   DEVELOPMENT

Polycomb protein Ezh2 regulates pancreatic  -cell Ink4a/Arf expression and regeneration in diabetes mellitus

(2009) H. Chen et al.   GENES & DEVELOPMENT

DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation

(2009) T. B. Miranda et al.   MOLECULAR CANCER THERAPEUTICS

In Brief

(2009)   NATURE REVIEWS NEUROSCIENCE

Ezh1 and Ezh2 Maintain Repressive Chromatin through Different Mechanisms

(2008) Raphael Margueron et al.   MOLECULAR CELL

Repression of E-cadherin by the polycomb group protein EZH2 in cancer

(2008) Q Cao et al.   ONCOGENE

Differentiation of Neural Stem Cells into Oligodendrocytes: Involvement of the Polycomb Group Protein Ezh2

(2008) Falak Sher et al.   STEM CELLS