Discovery of a New-Generation S-Adenosylmethionine-Noncompetitive Covalent Inhibitor Targeting the Lysine Methyltransferase Enhancer of Zeste Homologue 2

Discovery of a Novel Covalent EZH2 Inhibitor Based on Tazemetostat Scaffold for the Treatment of Ovarian Cancer

(2023) Qiangsheng Zhang et al.   Journal of Medicinal Chemistry

Covalent inhibitors of EZH2: Design, synthesis and evaluation

(2022) Qiangsheng Zhang et al.   BIOMEDICINE & PHARMACOTHERAPY

Targeting Enhancer of Zeste Homolog 2 for the Treatment of Hematological Malignancies and Solid Tumors: Candidate Structure–Activity Relationships Insights and Evolution Prospects

(2022) Juan Xia et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design and Synthesis of Dual EZH2/BRD4 Inhibitors to Target Solid Tumors

(2022) Zhirong Guo et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Aided Design, Synthesis, and Biological Evaluation of Potent and Selective Non-Nucleoside Inhibitors Targeting Protein Arginine Methyltransferase 5

(2022) Deqin Rong et al.   JOURNAL OF MEDICINAL CHEMISTRY

EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis

(2022) Jun Wang et al.   NATURE CELL BIOLOGY

Discovery of precision targeting EZH2 degraders for triple-negative breast cancer

(2022) Cheng Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

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

(2022) Jia Zeng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of the First-in-Class G9a/GLP Covalent Inhibitors

(2022) Kwang-Su Park et al.   JOURNAL OF MEDICINAL CHEMISTRY

Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease

(2021) Kamakoti P. Bhat et al.   NATURE REVIEWS DRUG DISCOVERY

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

Design and Characterization of a Pyridone-Containing EZH2 Inhibitor Phosphate Prodrug

(2021) Pei-Pei Kung et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting Epigenetic Regulators with Covalent Small-Molecule Inhibitors

(2021) Yi Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhibition of EZH2 primes the cardiac gene activation via removal of epigenetic repression during human direct cardiac reprogramming

(2021) Yawen Tang et al.   Stem Cell Research

FIRST‐IN‐HUMAN STUDY OF THE EZH1 AND EZH2 DUAL INHIBITOR VALEMETOSTAT TOSYLATE (DS‐3201B) IN PATIENTS WITH RELAPSED OR REFRACTORY NON‐HODGKIN LYMPHOMAS

(2021) K Ishitsuka et al.   HEMATOLOGICAL ONCOLOGY

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

Discovery of Cysteine-targeting Covalent Protein Kinase Inhibitors

(2021) Xiaoyun Lu et al.   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

Discovery of Di- and Trihaloacetamides as Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity

(2021) Chunlong Ma et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Discovery of M-808 as a Highly Potent, Covalent, Small-Molecule Inhibitor of the Menin–MLL Interaction with Strong In Vivo Antitumor Activity

(2020) Shilin Xu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a First-in-Class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor

(2020) Yudao Shen et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

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

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

Covalent Inhibitors of Protein–Protein Interactions Targeting Lysine, Tyrosine, or Histidine Residues

(2019) Luca Gambini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a first-in-class EZH2 selective degrader

(2019) Anqi Ma et al.   Nature Chemical Biology

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

(2018) Malik Bisserier et al.   BLOOD

Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study

(2018) Antoine Italiano et al.   LANCET ONCOLOGY

Histone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer

(2018) Bayley A. Jones et al.   MOLECULAR CANCER THERAPEUTICS

Epigenetic drug discovery: a success story for cofactor interference

(2018) A. Ganesan   PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES

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

Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology

(2018) Matthias Gehringer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Engineering of Irreversible Inhibitors against Histone Lysine Demethylase KDM5A

(2018) John R. Horton et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

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

(2016) Kevin W. Kuntz 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

Structure-Based Design of a Covalent Inhibitor of the SET Domain-Containing Protein 8 (SETD8) Lysine Methyltransferase

(2016) Kyle V. Butler et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting EZH2 in cancer

(2016) Kimberly H Kim et al.   NATURE MEDICINE

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

(2015) L. Jiao et al.   SCIENCE

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

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

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

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

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

Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks

(2011) Frank W. Schmitges et al.   MOLECULAR CELL

The Polycomb complex PRC2 and its mark in life

(2011) Raphaël Margueron et al.   NATURE

Tobacco Smoke Induces Polycomb-Mediated Repression of Dickkopf-1 in Lung Cancer Cells

(2009) M. Hussain et al.   CANCER RESEARCH