Targeting EZH2 for cancer therapy: From current progress to novel strategies

Covalent inhibitors of EZH2: Design, synthesis and evaluation

(2022) Qiangsheng Zhang et al.   BIOMEDICINE & PHARMACOTHERAPY

Targeting EZH2 as cancer therapy

(2021) Shunsuke Hanaki et al.   JOURNAL OF BIOCHEMISTRY

Long non-coding RNA linc00665 inhibits CDKN1C expression by binding to EZH2 and affects cisplatin sensitivity of NSCLC cells

(2021) Daolu Yang et al.   Molecular Therapy-Nucleic Acids

Dual EZH2 and G9a inhibition suppresses multiple myeloma cell proliferation by regulating the interferon signal and IRF4-MYC axis

(2021) Kazuya Ishiguro et al.   Cell Death Discovery

The noncanonical role of EZH2 in cancer

(2021) Jinhua Huang et al.   CANCER SCIENCE

Design and Synthesis of EZH2-Based PROTACs to Degrade the PRC2 Complex for Targeting the Noncatalytic Activity of EZH2

(2021) Zhihao Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Histone Methyltransferase EZH2: A Potential Therapeutic Target for Kidney Diseases

(2021) Tingting Li et al.   Frontiers in Physiology

The Endothelium as a Target for Anti-Atherogenic Therapy: A Focus on the Epigenetic Enzymes EZH2 and SIRT1

(2021) Jolien Fledderus et al.   Journal of Personalized Medicine

Polycomb-Group proteins in the initiation and progression of cancer

(2021) Xiujuan Zhao et al.   Journal of Genetics and Genomics

Finding an easy way to harmonize: a review of advances in clinical research and combination strategies of EZH2 inhibitors

(2021) Chen Li et al.   Clinical Epigenetics

Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma

(2021) Yalin Tu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of First-in-Class Dual PARP and EZH2 Inhibitors for Triple-Negative Breast Cancer with Wild-Type BRCA

(2021) Cheng Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Guided Development of Small-Molecule PRC2 Inhibitors Targeting EZH2–EED Interaction

(2021) Daohai Du et al.   JOURNAL OF MEDICINAL CHEMISTRY

Polycomb Repressive Complex 2 Modulation through the Development of EZH2–EED Interaction Inhibitors and EED Binders

(2021) Stefano Tomassi et al.   JOURNAL OF MEDICINAL CHEMISTRY

EZH2 inhibition confers PIK3CA-driven lung tumors enhanced sensitivity to PI3K inhibition

(2021) Fan Chen et al.   CANCER LETTERS

Histone methyltransferase EZH2 epigenetically affects CCNA1 expression in acute myeloid leukemia

(2021) Xiaoyang Yang et al.   CELLULAR SIGNALLING

DYRK1A inhibitors for disease therapy: Current status and perspectives

(2021) Tong Liu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of IHMT-EZH2-115 as a Potent and Selective Enhancer of Zeste Homolog 2 (EZH2) Inhibitor for the Treatment of B-Cell Lymphomas

(2021) Bin Zhou et al.   JOURNAL OF MEDICINAL CHEMISTRY

The molecular mechanisms and therapeutic potential of EZH2 in breast cancer

(2021) Sara Adibfar et al.   LIFE SCIENCES

Tumor-suppressive function of EZH2 is through inhibiting glutaminase

(2021) Yongfeng Liu et al.   Cell Death & Disease

Novel Natural Inhibitors Targeting Enhancer of Zeste Homolog 2: A Comprehensive Structural Biology Research

(2021) Weihang Li et al.   Frontiers in Oncology

EZH2 Inhibitor Enhances the STING Agonist‒Induced Antitumor Immunity in Melanoma

(2021) Tianxiao Xu et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Design and synthesis of (E)-1,2-diphenylethene-based EZH2 inhibitors

(2020) Hualong He et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

EZH2 Inhibition Sensitizes CARM1-High, Homologous Recombination Proficient Ovarian Cancers to PARP Inhibition

(2020) Sergey Karakashev et al.   CANCER CELL

EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair

(2020) Allyson E. Koyen et al.   ONCOGENE

Design, Synthesis, and Pharmacological Evaluation of Second Generation EZH2 Inhibitors with Long Residence Time

(2020) Avinash Khanna et al.   ACS Medicinal Chemistry Letters

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

(2020) Annalisa Romanelli et al.   ACS Medicinal Chemistry Letters

EZH2-Targeted Therapies in Cancer: Hype or a Reality

(2020) Marie-Lisa Eich et al.   CANCER RESEARCH

Combined EZH2 and Bcl-2 inhibitors as precision therapy for genetically defined DLBCL subtypes

(2020) Hanna Scholze et al.   Blood Advances

EZH2 promotes the expression of LPA1 by mediating microRNA-139 promoter methylation to accelerate the development of ovarian cancer

(2020) Dongbo Wu et al.   Cancer Cell International

No Easy Way Out for EZH2: Its Pleiotropic, Noncanonical Effects on Gene Regulation and Cellular Function

(2020) Jun Wang et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

EZH2 as a Potential Target for NAFLD Therapy

(2020) Hyun Jung Lim et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Small Molecule Approaches for Targeting the Polycomb Repressive Complex 2 (PRC2) in Cancer

(2020) M. Cynthia Martin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells

(2019) Xiaofu Qiu et al.   BMC CANCER

EZH2 promotes gastric cancer cells proliferation by repressing p21 expression

(2019) Jiewei Xu et al.   PATHOLOGY RESEARCH AND PRACTICE

Identification of a chemical modulator of EZH2-mediated silencing by cell-based high-throughput screening assay

(2019) Akihiro Murashima et al.   JOURNAL OF BIOCHEMISTRY

Decreased expression of NEDD4L contributes to NSCLC progression and metastasis

(2019) Xuming Wang et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Precision Targeting with EZH2 and HDAC Inhibitors in Epigenetically Dysregulated Lymphomas

(2019) Jennifer K Lue et al.   CLINICAL CANCER RESEARCH

Inhibition of enhancer of zeste homolog 2 (EZH2) overcomes enzalutamide-resistance in castration-resistance prostate cancer

(2019) Yunfeng Bai et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phase 1 study of the novel enhancer of zeste homolog 2 (EZH2) inhibitor GSK2816126 in patients with advanced hematological and solid tumors

(2019) Timothy A. Yap et al.   CLINICAL CANCER RESEARCH

Targeting EZH2 enhances antigen presentation, antitumor immunity and circumvents anti-PD-1 resistance in head and neck cancers

(2019) Liye Zhou et al.   CLINICAL CANCER RESEARCH

Overexpression of Histone H3 Lysine 27 Trimethylation Is Associated with Aggressiveness and Dedifferentiation of Thyroid Cancer

(2019) Chia-Chi Tsai et al.   ENDOCRINE PATHOLOGY

HOXA11-AS promotes the migration and invasion of hepatocellular carcinoma cells by inhibiting miR-124 expression by binding to EZH2

(2019) Wen-long Zhang et al.   Human Cell

Degradation of proteins by PROTACs and other strategies

(2019) Yang Wang et al.   Acta Pharmaceutica Sinica B

The role and prospect of JMJD3 in stem cells and cancer

(2019) Xiaojiao Yin et al.   BIOMEDICINE & PHARMACOTHERAPY

EZH2 negatively regulates PD-L1 expression in hepatocellular carcinoma

(2019) Gang Xiao et al.   Journal for ImmunoTherapy of Cancer

Identification and Assessments of Novel and Potent Small-Molecule Inhibitors of EED–EZH2 Interaction of Polycomb Repressive Complex 2 by Computational Methods and Biological Evaluations

(2019) Kongkai Zhu et al.   CHEMICAL & PHARMACEUTICAL BULLETIN

Discovery of a first-in-class EZH2 selective degrader

(2019) Anqi Ma et al.   Nature Chemical Biology

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

(2019) Giulia Stazi et al.   Clinical Epigenetics

Mechanisms of resistance to EZH2 inhibitors in diffuse large B-cell lymphomas

(2018) Malik Bisserier et al.   BLOOD

PARP Inhibitors in Ovarian Cancer: A Trailblazing and Transformative Journey

(2018) Panagiotis A. Konstantinopoulos et al.   CLINICAL CANCER RESEARCH

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

Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors

(2018) Xun Huang et al.   CELL

Modulation of EZH2 expression in T cells improves efficacy of anti–CTLA-4 therapy

(2018) Sangeeta Goswami et al.   JOURNAL OF CLINICAL INVESTIGATION

Histone deacetylase inhibitors synergizes with catalytic inhibitors of EZH2 to exhibit anti-tumor activity in small cell carcinoma of the ovary, hypercalcemic type

(2018) Yemin Wang et al.   MOLECULAR CANCER THERAPEUTICS

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

(2018) Rossella Fioravanti et al.   CHEMICAL RECORD

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

Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones?

(2017) Ian Churcher   JOURNAL OF MEDICINAL CHEMISTRY

EZH2 contributes to the response to PARP inhibitors through its PARP-mediated poly-ADP ribosylation in breast cancer

(2017) H Yamaguchi et al.   ONCOGENE

Current status of poly(ADP-ribose) polymerase inhibitors and future directions

(2017) Akihiro Ohmoto et al.   OncoTargets and Therapy

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

(2017) Evelina Miele et al.   Oncotarget

Combined inhibition of EZH2 and histone deacetylases as a potential epigenetic therapy for non-small-cell lung cancer cells

(2016) Taichi Takashina et al.   CANCER SCIENCE

Targeting protein–protein interactions, a wide open field for drug design

(2016) May Bakail et al.   COMPTES RENDUS CHIMIE

Emerging roles for Polycomb proteins in cancer

(2016) Diego Pasini et al.   CURRENT OPINION IN GENETICS & DEVELOPMENT

Loss ofEzh2synergizes withJAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis

(2016) Takafumi Shimizu et al.   JOURNAL OF EXPERIMENTAL MEDICINE

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

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

(2016) Kevin W. Kuntz et al.   JOURNAL OF MEDICINAL CHEMISTRY

Counting on natural products for drug design

(2016) Tiago Rodrigues et al.   Nature Chemistry

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

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

(2016) H. Zhang et al.   Cancer Discovery

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

Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-dependent manner

(2015) M. Mochizuki-Kashio et al.   BLOOD

Overexpression of EZH2 associates with a poor prognosis in chronic lymphocytic leukemia

(2015) Doralina do Amaral Rabello et al.   BLOOD CELLS MOLECULES AND DISEASES

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 sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors

(2015) Christine M. Fillmore et al.   NATURE

Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2

(2015) L. Jiao et al.   SCIENCE

Interference with endogenous EZH2 reverses the chemotherapy drug resistance in cervical cancer cells partly by up-regulating Dicer expression

(2015) Liqiong Cai et al.   TUMOR BIOLOGY

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

Design, synthesis and biological evaluation of novel 1-methyl-3-oxo-2,3,5,6,7,8-hexahydroisoquinolins as potential EZH2 inhibitors

(2015) Lidan Zhang et al.   RSC Advances

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

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

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

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

Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2

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

EZH2-Mediated Inactivation of IFN-γ-JAK-STAT1 Signaling Is an Effective Therapeutic Target in MYC-Driven Prostate Cancer

(2014) Zhen Ning Wee et al.   Cell Reports

PARP inhibition and synthetic lethality in ovarian cancer

(2014) Ramez N Eskander et al.   Expert Review of Clinical Pharmacology

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

(2013) Wendy Béguelin et al.   CANCER CELL

Phosphorylation of EZH2 Activates STAT3 Signaling via STAT3 Methylation and Promotes Tumorigenicity of Glioblastoma Stem-like Cells

(2013) Eunhee Kim et al.   CANCER CELL

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

Features of protein–protein interactions that translate into potent inhibitors: topology, surface area and affinity

(2012) Matthew C. Smith et al.   EXPERT REVIEWS IN MOLECULAR MEDICINE

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

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

EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells Is Polycomb-Independent

(2012) K. Xu et al.   SCIENCE

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

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

Context-Specific Regulation of NF-κB Target Gene Expression by EZH2 in Breast Cancers

(2011) Shuet Theng Lee et al.   MOLECULAR CELL

The Polycomb complex PRC2 and its mark in life

(2011) Raphaël Margueron et al.   NATURE

Targeting protein–protein interactions for therapeutic intervention: a challenge for the future

(2010) Giovanna Zinzalla et al.   Future Medicinal Chemistry

Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells

(2009) W. Fiskus et al.   BLOOD

Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success

(2009) Frank Lovering et al.   JOURNAL OF MEDICINAL CHEMISTRY

Roles of the EZH2 histone methyltransferase in cancer epigenetics

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