Targeting epigenetic protein–protein interactions with small-molecule inhibitors

Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer

(2020) Emily J. Faivre et al.   NATURE

Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy

(2019) Gloria Manzotti et al.   Cancers

Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity

(2019) Erin R. Aho et al.   Cell Reports

Molecular Mechanisms Directing PRC2 Recruitment and H3K27 Methylation

(2019) Anne Laugesen et al.   MOLECULAR CELL

Discovery of a Potent and Selective Fragment-like Inhibitor of Methyllysine Reader Protein Spindlin 1 (SPIN1)

(2019) Yan Xiong et al.   JOURNAL OF MEDICINAL CHEMISTRY

Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3

(2019) Jark Böttcher et al.   Nature Chemical Biology

Bromodomains: a new target class for drug development

(2019) Andrea G. Cochran et al.   NATURE REVIEWS DRUG DISCOVERY

Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing

(2019) Hagar F. Moussa et al.   Nature Communications

A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function

(2019) Vincent Fagan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting non-bromodomain chromatin readers

(2019) Cheryl H. Arrowsmith et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Bromodomain biology and drug discovery

(2019) Nilesh Zaware et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Epigenetic Programing of B-Cell Lymphoma by BCL6 and Its Genetic Deregulation

(2019) Haopeng Yang et al.   Frontiers in Cell and Developmental Biology

A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia

(2019) Andrei V. Krivtsov et al.   CANCER CELL

Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia

(2019) Szymon Klossowski et al.   JOURNAL OF CLINICAL INVESTIGATION

Discovery and Structure-Based Optimization of Potent and Selective WD Repeat Domain 5 (WDR5) Inhibitors Containing a Dihydroisoquinolinone Bicyclic Core

(2019) Jianhua Tian et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of H3K36-methylated nucleosome–PWWP complex reveals multivalent cross-gyre binding

(2019) Haibo Wang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach

(2018) Anastasia Amato et al.   ACS Chemical Biology

Discovery of an Irreversible and Cell-Active BCL6 Inhibitor Selectively Targeting Cys53 Located at the Protein–Protein Interaction Interface

(2018) Tomoya Sameshima et al.   BIOCHEMISTRY

Structural plasticity of the TDRD3 Tudor domain probed by a fragment screening hit

(2018) Jiuyang Liu et al.   FEBS Journal

Recognition of histone acetylation by the GAS41 YEATS domain promotes H2A.Z deposition in non-small cell lung cancer

(2018) Chih-Chao Hsu et al.   GENES & DEVELOPMENT

Identification of Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design

(2018) Huimin Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

SPIN1 promotes tumorigenesis by blocking the uL18 (universal large ribosomal subunit protein 18)-MDM2-p53 pathway in human cancer

(2018) Ziling Fang et al.   eLife

Gas41 links histone acetylation to H2A.Z deposition and maintenance of embryonic stem cell identity

(2018) Chih-Chao Hsu et al.   Cell Discovery

GAS41 Recognizes Diacetylated Histone H3 through a Bivalent Binding Mode

(2018) Hyo Je Cho et al.   ACS Chemical Biology

ENL: structure, function, and roles in hematopoiesis and acute myeloid leukemia

(2018) Jianbiao Zhou et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

WD40 Repeat Proteins: Signalling Scaffold with Diverse Functions

(2018) Buddhi Prakash Jain et al.   PROTEIN JOURNAL

Targeting Brd4 for cancer therapy: inhibitors and degraders

(2018) Yingchao Duan et al.   MedChemComm

miR-409 inhibits human non-small cell lung cancer progression by directly targeting SPIN1

(2018) Qi Song et al.   Molecular Therapy-Nucleic Acids

Development of a Novel B-Cell Lymphoma 6 (BCL6) PROTAC To Provide Insight into Small Molecule Targeting of BCL6

(2018) William McCoull et al.   ACS Chemical Biology

Discovery of an MLLT1/3 YEATS Domain Chemical Probe

(2018) Moses Moustakim et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL)

(2018) David Heidenreich et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking

(2018) Xin Li et al.   Nature Chemical Biology

Engagement of DNA and H3K27me3 by the CBX8 chromodomain drives chromatin association

(2018) Katelyn E Connelly et al.   NUCLEIC ACIDS RESEARCH

The Histone H3 Lysine 4 Presenter WDR5 as an Oncogenic Protein and Novel Epigenetic Target in Cancer

(2018) Kebin Lu et al.   Frontiers in Oncology

Epigenetic regulation by the menin pathway

(2017) Zijie Feng et al.   ENDOCRINE-RELATED CANCER

Polycomb Repressor Complex 2 in Genomic Instability and Cancer

(2017) Zoe Veneti et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Structure, mechanism, and regulation of polycomb repressive complex 2

(2017) Lindsay E. Moritz et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Biological function and histone recognition of family IV bromodomain-containing proteins

(2017) Jonathan T. Lloyd et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Discovery of Pyrazolo[1,5-a]pyrimidine B-Cell Lymphoma 6 (BCL6) Binders and Optimization to High Affinity Macrocyclic Inhibitors

(2017) William McCoull et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

(2017) Hacer Karatas et al.   JOURNAL OF MEDICINAL CHEMISTRY

YEATS Domain—A Histone Acylation Reader in Health and Disease

(2017) Dan Zhao et al.   JOURNAL OF MOLECULAR BIOLOGY

The Multiple Facets of PRC2 Alterations in Cancers

(2017) M. Wassef et al.   JOURNAL OF MOLECULAR BIOLOGY

Disease Association and Druggability of WD40 Repeat Proteins

(2017) Richard Song et al.   JOURNAL OF PROTEOME RESEARCH

Transcription control by the ENL YEATS domain in acute leukaemia

(2017) Michael A. Erb et al.   NATURE

ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia

(2017) Liling Wan et al.   NATURE

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

WD40 repeat domain proteins: a novel target class?

(2017) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

Epigenetic plasticity and the hallmarks of cancer

(2017) William A. Flavahan et al.   SCIENCE

Mechanisms Regulating PRC2 Recruitment and Enzymatic Activity

(2017) Daniel Holoch et al.   TRENDS IN BIOCHEMICAL SCIENCES

YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer

(2017) Wenyi Mi et al.   Nature Communications

Tudor Domain Containing Protein 3 Promotes Tumorigenesis and Invasive Capacity of Breast Cancer Cells

(2017) Alan Morettin et al.   Scientific Reports

Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6

(2017) Nina Kerres et al.   Cell Reports

YEATS2 is a selective histone crotonylation reader

(2016) Dan Zhao et al.   CELL RESEARCH

A PWWP Domain of Histone-LysineN-Methyltransferase NSD2 Binds to Dimethylated Lys-36 of Histone H3 and Regulates NSD2 Function at Chromatin

(2016) Saumya M. Sankaran et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma

(2016) Mariano G. Cardenas et al.   JOURNAL OF CLINICAL INVESTIGATION

Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1)

(2016) Matthäus Getlik et al.   JOURNAL OF MEDICINAL CHEMISTRY

Suppression of SPIN1-mediated PI3K-Akt pathway by miR-489 increases chemosensitivity in breast cancer

(2016) Xu Chen et al.   JOURNAL OF PATHOLOGY

Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function

(2016) Arnob Dutta et al.   MOLECULAR CELL

Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain

(2016) Yuanyuan Li et al.   MOLECULAR CELL

A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1

(2016) Jacob I Stuckey et al.   Nature Chemical Biology

Twenty years on: the impact of fragments on drug discovery

(2016) Daniel A. Erlanson et al.   NATURE REVIEWS DRUG DISCOVERY

The molecular hallmarks of epigenetic control

(2016) C. David Allis et al.   NATURE REVIEWS GENETICS

Identification of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening platform

(2016) Tobias Wagner et al.   NUCLEIC ACIDS RESEARCH

LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer

(2016) Anamika Basu et al.   PLoS One

Structural Insights into Histone Crotonyl-Lysine Recognition by the AF9 YEATS Domain

(2016) Qiang Zhang et al.   STRUCTURE

Structure-Guided Discovery of Selective Antagonists for the Chromodomain of Polycomb Repressive Protein CBX7

(2016) Chunyan Ren et al.   ACS Medicinal Chemistry Letters

BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization

(2016) Felicia Gray et al.   Nature Communications

Role of the Polycomb Repressive Complex 2 (PRC2) in Transcriptional Regulation and Cancer

(2016) Anne Laugesen et al.   Cold Spring Harbor Perspectives in Medicine

Identification of a Fragment-like Small Molecule Ligand for the Methyl-lysine Binding Protein, 53BP1

(2015) Michael T. Perfetti et al.   ACS Chemical Biology

Pharmacologic Inhibition of the Menin-MLL Interaction Blocks Progression of MLL Leukemia In Vivo

(2015) Dmitry Borkin et al.   CANCER CELL

Small-Molecule Modulators of Methyl-Lysine Binding for the CBX7 Chromodomain

(2015) Chunyan Ren et al.   CHEMISTRY & BIOLOGY

Polycomb Group (PcG) Proteins and Human Cancers: Multifaceted Functions and Therapeutic Implications

(2015) Wei Wang et al.   MEDICINAL RESEARCH REVIEWS

NSD3-Short Is an Adaptor Protein that Couples BRD4 to the CHD8 Chromatin Remodeler

(2015) Chen Shen et al.   MOLECULAR CELL

Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia

(2015) Florian Grebien et al.   Nature Chemical Biology

Molecular Basis of Histone Tail Recognition by Human TIP5 PHD Finger and Bromodomain of the Chromatin Remodeling Complex NoRC

(2015) Cynthia Tallant et al.   STRUCTURE

Competitive Binding of a Benzimidazole to the Histone-Binding Pocket of the Pygo PHD Finger

(2014) Thomas C. R. Miller et al.   ACS Chemical Biology

Hot spot-based design of small-molecule inhibitors for protein–protein interactions

(2014) Wenxing Guo et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation

(2014) Yuanyuan Li et al.   CELL

Crystal structure of human BS69 Bromo-ZnF-PWWP reveals its role in H3K36me3 nucleosome binding

(2014) Juncheng Wang et al.   CELL RESEARCH

Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality

(2014) Michelle R. Arkin et al.   CHEMISTRY & BIOLOGY

Biotransformation and bioactivation reactions of alicyclic amines in drug molecules

(2014) Jayaprakasam Bolleddula et al.   DRUG METABOLISM REVIEWS

Challenges and opportunities in targeting the menin–MLL interaction

(2014) Tomasz Cierpicki et al.   Future Medicinal Chemistry

Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1

(2014) X. Su et al.   GENES & DEVELOPMENT

Targeting protein-protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies?

(2014) Tomasz Cierpicki et al.   IMMUNOLOGICAL REVIEWS

Chromodomain Antagonists That Target the Polycomb-Group Methyllysine Reader Protein Chromobox Homolog 7 (CBX7)

(2014) Chakravarthi Simhadri et al.   JOURNAL OF MEDICINAL CHEMISTRY

53BP1, BRCA1, and the Choice between Recombination and End Joining at DNA Double-Strand Breaks

(2014) J. M. Daley et al.   MOLECULAR AND CELLULAR BIOLOGY

Arginine Methylation Facilitates the Recruitment of TOP3B to Chromatin to Prevent R Loop Accumulation

(2014) Yanzhong Yang et al.   MOLECULAR CELL

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome

(2014) Robert K. McGinty et al.   NATURE

BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence

(2014) Lei Gu et al.   NATURE GENETICS

Structure and function of the nucleosome-binding PWWP domain

(2014) Su Qin et al.   TRENDS IN BIOCHEMICAL SCIENCES

PRC1 complex diversity: where is it taking us?

(2014) Jesús Gil et al.   TRENDS IN CELL BIOLOGY

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

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

Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain

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

Tudor: a versatile family of histone methylation ‘readers’

(2013) Rui Lu et al.   TRENDS IN BIOCHEMICAL SCIENCES

Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain

(2013) Rick van Nuland et al.   Epigenetics & Chromatin

A Hybrid Mechanism of Action for BCL6 in B Cells Defined by Formation of Functionally Distinct Complexes at Enhancers and Promoters

(2013) Katerina Hatzi et al.   Cell Reports

Fine-Tuning Multiprotein Complexes Using Small Molecules

(2012) Andrea D. Thompson et al.   ACS Chemical Biology

Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5

(2012) Guillermo Senisterra et al.   BIOCHEMICAL JOURNAL

Identification and Characterization of Small Molecule Inhibitors of a Plant Homeodomain Finger

(2012) Elise K. Wagner et al.   BIOCHEMISTRY

Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia

(2012) A. Shi et al.   BLOOD

Expanding the Number of ‘Druggable’ Targets: Non-Enzymes and Protein-Protein Interactions

(2012) Leah N. Makley et al.   Chemical Biology & Drug Design

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

Histone Recognition by Human Malignant Brain Tumor Domains

(2012) Nataliya Nady et al.   JOURNAL OF MOLECULAR BIOLOGY

High-Affinity, Small-Molecule Peptidomimetic Inhibitors of MLL1/WDR5 Protein–Protein Interaction

(2012) Hacer Karatas et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia

(2012) Jolanta Grembecka et al.   Nature Chemical Biology

Crystal Structure of TDRD3 and Methyl-Arginine Binding Characterization of TDRD3, SMN and SPF30

(2012) Ke Liu et al.   PLoS One

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

(2012) N. Yang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Linking DNA Methyltransferases to Epigenetic Marks and Nucleosome Structure Genome-wide in Human Tumor Cells

(2012) Bilian Jin et al.   Cell Reports

Structure and Mechanisms of Lysine Methylation Recognition by the Chromodomain in Gene Transcription

(2011) Kyoko L. Yap et al.   BIOCHEMISTRY

Regulation of chromatin by histone modifications

(2011) Andrew J Bannister et al.   CELL RESEARCH

Fragment screening to predict druggability (ligandability) and lead discovery success

(2011) Fredrik N.B. Edfeldt et al.   DRUG DISCOVERY TODAY

Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the expression of rRNA genes

(2011) Weixiang Wang et al.   EMBO REPORTS

Crystal Structure of Menin Reveals Binding Site for Mixed Lineage Leukemia (MLL) Protein

(2011) Marcelo J. Murai et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Small-Molecule Ligands of Methyl-Lysine Binding Proteins

(2011) J. Martin Herold et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cancer epigenetics reaches mainstream oncology

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

Structural and Histone Binding Ability Characterizations of Human PWWP Domains

(2011) Hong Wu et al.   PLoS One

Structure and function of WD40 domain proteins

(2011) Chao Xu et al.   Protein & Cell

Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

(2010) G. Mann et al.   BLOOD

MLL fusions: Pathways to leukemia

(2010) Han Liu et al.   CANCER BIOLOGY & THERAPY

A Small-Molecule Inhibitor of BCL6 Kills DLBCL Cells In Vitro and In Vivo

(2010) Leandro C. Cerchietti et al.   CANCER CELL

Loss of the CBX7 protein expression correlates with a more aggressive phenotype in pancreatic cancer

(2010) Eva Karamitopoulou et al.   EUROPEAN JOURNAL OF CANCER

Molecular Basis of the Mixed Lineage Leukemia-Menin Interaction

(2010) Jolanta Grembecka et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Recognition and Specificity Determinants of the Human Cbx Chromodomains

(2010) Lilia Kaustov et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Analysis of the Binding of Mixed Lineage Leukemia 1 (MLL1) and Histone 3 Peptides to WD Repeat Domain 5 (WDR5) for the Design of Inhibitors of the MLL1−WDR5 Interaction

(2010) Hacer Karatas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Allosteric Remodelling of the Histone H3 Binding Pocket in the Pygo2 PHD Finger Triggered by Its Binding to the B9L/BCL9 Co-Factor

(2010) Thomas C.R. Miller et al.   JOURNAL OF MOLECULAR BIOLOGY

Ring1B Compacts Chromatin Structure and Represses Gene Expression Independent of Histone Ubiquitination

(2010) Ragnhild Eskeland et al.   MOLECULAR CELL

Molecular Interplay of the Noncoding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a

(2010) Kyoko L. Yap et al.   MOLECULAR CELL

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1

(2010) Alessandro Vezzoli et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

L3MBTL1 polycomb protein, a candidate tumor suppressor in del(20q12) myeloid disorders, is essential for genome stability

(2010) N. Gurvich et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Protein-protein docking benchmark version 4.0

(2010) Howook Hwang et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

WD40 proteins propel cellular networks

(2010) Christian U. Stirnimann et al.   TRENDS IN BIOCHEMICAL SCIENCES

Ring1B Contains a Ubiquitin-Like Docking Module for Interaction with Cbx Proteins,

(2009) Irina Bezsonova et al.   BIOCHEMISTRY

Structures of the Dual Bromodomains of the P-TEFb-activating Protein Brd4 at Atomic Resolution

(2009) Friederike Vollmuth et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger

(2009) Gang G. Wang et al.   NATURE

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

(2009) Raphael Margueron et al.   NATURE

Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma

(2009) Paul A Northcott et al.   NATURE GENETICS

MBT domain proteins in development and disease

(2009) Roberto Bonasio et al.   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

Menin Critically Links MLL Proteins with LEDGF on Cancer-Associated Target Genes

(2008) Akihiko Yokoyama et al.   CANCER CELL

Decoding of Methylated Histone H3 Tail by the Pygo-BCL9 Wnt Signaling Complex

(2008) Marc Fiedler et al.   MOLECULAR CELL

Structure of a BCOR Corepressor Peptide in Complex with the BCL6 BTB Domain Dimer

(2008) Alexandru F. Ghetu et al.   MOLECULAR CELL

Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1

(2008) N Kalakonda et al.   ONCOGENE