Enhancer of zeste homolog 2 (EZH2) inhibitors

EZH2 inhibitors: a patent review (2014-2016)

(2017) Giulia Stazi et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

DUAL INHIBITION OF EZH2 AND HDAC IS SYNERGISTIC IN EZH2 DYSREGULATED LYMPHOMAS

(2017) J.K. Lue et al.   HEMATOLOGICAL ONCOLOGY

PRELIMINARY EVIDENCE OF A MOLECULAR PREDICTOR OF TAZEMETOSTAT RESPONSE, BEYOND EZH2 MUTATION, IN NHL PATIENTS VIA CHARACTERIZATION OF ARCHIVE TUMOR AND CIRCULATING TUMOR DNA

(2017) S.J. Blakemore et al.   HEMATOLOGICAL ONCOLOGY

INTERIM REPORT FROM A PHASE 2 MULTICENTER STUDY OF TAZEMETOSTAT, AN EZH2 INHIBITOR, IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMAS

(2017) F. Morschhauser et al.   HEMATOLOGICAL ONCOLOGY

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

EZH2 Inhibition by Tazemetostat Results in Altered Dependency on B-cell Activation Signaling in DLBCL

(2017) Dorothy Brach et al.   MOLECULAR CANCER THERAPEUTICS

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

EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop

(2017) Wendy Béguelin et al.   Nature Communications

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

(2017) Ling Li et al.   PLoS One

JAK2 exon 12 mutant mice display isolated erythrocytosis and changes in iron metabolism favoring increased erythropoiesis

(2016) Jean Grisouard et al.   BLOOD

EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis

(2016) Wendy Béguelin et al.   CANCER CELL

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

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

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

(2016) H. Zhang et al.   Cancer Discovery

Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma

(2016) Satoshi Kawano et al.   PLoS One

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

Targeting EZH2 and PRC2 dependence as novel anticancer therapy

(2015) Bowen Xu et al.   EXPERIMENTAL HEMATOLOGY

Oral Presentations

(2015)   HEMATOLOGICAL ONCOLOGY

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

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

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

Histone variants: dynamic punctuation in transcription

(2014) C. M. Weber et al.   GENES & DEVELOPMENT

Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2-Mutant Non-Hodgkin Lymphoma

(2014) S. K. Knutson et al.   MOLECULAR CANCER THERAPEUTICS

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

Breaking bad in the germinal center: how deregulation of BCL6 contributes to lymphomagenesis

(2014) Katerina Hatzi et al.   TRENDS IN MOLECULAR MEDICINE

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

Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis

(2013) Marieta Caganova 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

Germinal Centers

(2012) Gabriel D. Victora et al.   Annual Review of Immunology

Cancer Epigenetics: From Mechanism to Therapy

(2012) Mark A. Dawson et al.   CELL

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

Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia

(2012) Panagiotis Ntziachristos et al.   NATURE MEDICINE

Epigenetic protein families: a new frontier for drug discovery

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

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

Emerging Epigenetic Targets and Therapies in Cancer Medicine

(2012) Relja Popovic et al.   Cancer Discovery

Aberrations of EZH2 in Cancer

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

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

(2011) Ryan D. Morin et al.   NATURE

The Polycomb complex PRC2 and its mark in life

(2011) Raphaël Margueron et al.   NATURE

Cancer epigenetics reaches mainstream oncology

(2011) Manuel Rodríguez-Paredes et al.   NATURE MEDICINE

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

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

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

Roles of the EZH2 histone methyltransferase in cancer epigenetics

(2008) Jeffrey A. Simon et al.   MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS