Cancer epigenetics drug discovery and development: the challenge of hitting the mark

Long Residence Time Inhibition of EZH2 in Activated Polycomb Repressive Complex 2

(2014) Glenn S. Van Aller et al.   ACS Chemical Biology

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

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

Bromo-deaza-SAH: A potent and selective DOT1L inhibitor

(2013) Wenyu Yu et al.   BIOORGANIC & MEDICINAL CHEMISTRY

PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains

(2013) S. Picaud et al.   CANCER RESEARCH

Interplay between the Cancer Genome and Epigenome

(2013) Hui Shen et al.   CELL

Exploiting an Allosteric Binding Site of PRMT3 Yields Potent and Selective Inhibitors

(2013) Feng Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain

(2013) Lindsey I James et al.   Nature Chemical Biology

The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases

(2013) O A Romero et al.   ONCOGENE

BET Inhibition Silences Expression of MYCN and BCL2 and Induces Cytotoxicity in Neuroblastoma Tumor Models

(2013) Anastasia Wyce et al.   PLoS One

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

Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition

(2013) Alexandre Puissant et al.   Cancer Discovery

Epigenetic Resensitization to Platinum in Ovarian Cancer

(2012) D. Matei et al.   CANCER RESEARCH

Conformational Adaptation Drives Potent, Selective and Durable Inhibition of the Human Protein Methyltransferase DOT1L

(2012) Aravind Basavapathruni et al.   Chemical Biology & Drug Design

Identification of a Chemical Probe for Bromo and Extra C-Terminal Bromodomain Inhibition through Optimization of a Fragment-Derived Hit

(2012) Paul V. Fish et al.   JOURNAL OF MEDICINAL CHEMISTRY

Abrogation of MLL–AF10 and CALM–AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l

(2012) L Chen et al.   LEUKEMIA

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

(2012) Michael T. McCabe et al.   NATURE

Epigenetic protein families: a new frontier for drug discovery

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

Targeting Epigenetic Readers in Cancer

(2012) Mark A. Dawson et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors

(2012) Wenyu Yu et al.   Nature Communications

Biochemical Characterization of Human SET and MYND Domain-Containing Protein 2 Methyltransferase

(2011) Jiaquan Wu et al.   BIOCHEMISTRY

Selective Killing of Mixed Lineage Leukemia Cells by a Potent Small-Molecule DOT1L Inhibitor

(2011) Scott R. Daigle et al.   CANCER CELL

MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L

(2011) Kathrin M. Bernt et al.   CANCER CELL

BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc

(2011) Jake E. Delmore et al.   CELL

Discovery and Characterization of Small Molecule Inhibitors of the BET Family Bromodomains

(2011) Chun-wa Chung et al.   JOURNAL OF MEDICINAL CHEMISTRY

Selective Inhibitors of Histone Methyltransferase DOT1L: Design, Synthesis, and Crystallographic Studies

(2011) Yuan Yao et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

NSD2 Links Dimethylation of Histone H3 at Lysine 36 to Oncogenic Programming

(2011) Alex J. Kuo et al.   MOLECULAR CELL

Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

(2011) Mark A. Dawson et al.   NATURE

A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells

(2011) Masoud Vedadi et al.   Nature Chemical Biology

Targeting MYC dependence in cancer by inhibiting BET bromodomains

(2011) J. A. Mertz et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non-Small Cell Lung Cancer

(2011) R. A. Juergens et al.   Cancer Discovery

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

The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells

(2010) E. Martinez-Garcia et al.   BLOOD

Epigenetic Antagonism between Polycomb and SWI/SNF Complexes during Oncogenic Transformation

(2010) Boris G. Wilson et al.   CANCER CELL

Quantitative Mass Spectrometry of Histones H3.2 and H3.3 inSuz12-deficient Mouse Embryonic Stem Cells Reveals Distinct, Dynamic Post-translational Modifications at Lys-27 and Lys-36

(2010) Hye Ryung Jung et al.   MOLECULAR & CELLULAR PROTEOMICS

Suppression of inflammation by a synthetic histone mimic

(2010) Edwige Nicodeme et al.   NATURE

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes

(2010) Gorica Nikoloski 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

Genomic Analysis Using High-Density Single Nucleotide Polymorphism-Based Oligonucleotide Arrays and Multiplex Ligation-Dependent Probe Amplification Provides a Comprehensive Analysis of INI1/SMARCB1 in Malignant Rhabdoid Tumors

(2009) E. M. Jackson et al.   CLINICAL CANCER RESEARCH

The molecular biology of mixed lineage leukemia

(2009) R. K. Slany   HAEMATOLOGICA

The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate

(2009) Yan Li et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Role of the polycomb protein EED in the propagation of repressive histone marks

(2009) Raphael Margueron et al.   NATURE

Causes and consequences of microRNA dysregulation in cancer

(2009) Carlo M. Croce   NATURE REVIEWS GENETICS

Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia

(2009) Dorothee Mueller et al.   PLOS BIOLOGY

Demystified molecular pathology of NUT midline carcinomas

(2008) C. A. French   JOURNAL OF CLINICAL PATHOLOGY

The multiple myeloma associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity

(2007) J. Lauring et al.   BLOOD