Bromodomain biology and drug discovery

A chemical toolbox for the study of bromodomains and epigenetic signaling

(2019) Qin Wu et al.   Nature Communications

Targeting non-bromodomain chromatin readers

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

Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors

(2018) Jeremy Lewin et al.   JOURNAL OF CLINICAL ONCOLOGY

Plasticity in binding confers selectivity in ligand-induced protein degradation

(2018) Radosław P. Nowak et al.   Nature Chemical Biology

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

(2018) Lara N. Gechijian et al.   Nature Chemical Biology

Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth

(2018) Chunyan Ren et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes

(2018) Nazar Mashtalir et al.   CELL

Transcription factor dimerization activates the p300 acetyltransferase

(2018) Esther Ortega et al.   NATURE

Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation

(2017) Ka Lung Cheung et al.   MOLECULAR CELL

BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice

(2017) Kalung Cheung et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Structure of the ZMYND8/Drebrin Complex Suggests a Cytoplasmic Sequestering Mechanism of ZMYND8 by Drebrin

(2017) Ningning Yao et al.   STRUCTURE

A Chemical Probe for the ATAD2 Bromodomain

(2016) Paul Bamborough et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Potent and selective bivalent inhibitors of BET bromodomains

(2016) Michael J Waring et al.   Nature Chemical Biology

Design and characterization of bivalent BET inhibitors

(2016) Minoru Tanaka et al.   Nature Chemical Biology

Structural Mechanism of Transcriptional Regulator NSD3 Recognition by the ET Domain of BRD4

(2016) Qiang Zhang et al.   STRUCTURE

ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication

(2016) Seong Joo Koo et al.   Oncotarget

Multivalent Histone and DNA Engagement by a PHD/BRD/PWWP Triple Reader Cassette Recruits ZMYND8 to K14ac-Rich Chromatin

(2016) Pavel Savitsky et al.   Cell Reports

The Bromodomain: A New Target in Emerging Epigenetic Medicine

(2015) Steven G. Smith et al.   ACS Chemical Biology

LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor

(2015) Peter G. K. Clark et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Protein Lysine Acetylation by p300/CBP

(2015) Beverley M. Dancy et al.   CHEMICAL REVIEWS

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B

(2015) Peiling Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

9H-Purine Scaffold Reveals Induced-Fit Pocket Plasticity of the BRD9 Bromodomain

(2015) Sarah Picaud et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure Enabled Design of BAZ2-ICR, A Chemical Probe Targeting the Bromodomains of BAZ2A and BAZ2B

(2015) Ludovic Drouin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors

(2015) Emmanuel H. Demont et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition

(2015) Natalie H. Theodoulou et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor

(2015) Wylie S. Palmer et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2015) Chen Shen et al.   MOLECULAR CELL

Design and synthesis of potent and selective inhibitors of BRD7 and BRD9 bromodomains

(2015) Duncan A. Hay et al.   MedChemComm

Tumour suppressor TRIM33 targets nuclear β-catenin degradation

(2015) Jianfei Xue et al.   Nature Communications

Acetyl-lysine Binding Site of Bromodomain-Containing Protein 4 (BRD4) Interacts with Diverse Kinase Inhibitors

(2014) Stuart W. J. Ember et al.   ACS Chemical Biology

Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer

(2014) Jian Shi et al.   CANCER CELL

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

(2014) Yuanyuan Li et al.   CELL

Privileged Diazepine Compounds and Their Emergence as Bromodomain Inhibitors

(2014) Steven G. Smith et al.   CHEMISTRY & BIOLOGY

Selective Chemical Modulation of Gene Transcription Favors Oligodendrocyte Lineage Progression

(2014) Mar Gacias et al.   CHEMISTRY & BIOLOGY

Fragment-Based Screening of the Bromodomain of ATAD2

(2014) Mary J. Harner et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Discovery of I-BET726 (GSK1324726A), a Potent Tetrahydroquinoline ApoA1 Up-Regulator and Selective BET Bromodomain Inhibitor

(2014) Romain Gosmini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma

(2014) A Moros et al.   LEUKEMIA

ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression

(2014) Hong Wen et al.   NATURE

Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer

(2014) Irfan A. Asangani et al.   NATURE

Targeting bromodomains: epigenetic readers of lysine acetylation

(2014) Panagis Filippakopoulos et al.   NATURE REVIEWS DRUG DISCOVERY

The bromodomain and extra-terminal inhibitor CPI203 enhances the antiproliferative effects of rapamycin on human neuroendocrine tumors

(2014) C Wong et al.   Cell Death & Disease

1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain

(2014) Emmanuel H. Demont et al.   ACS Medicinal Chemistry Letters

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

(2013) S. Picaud et al.   CANCER RESEARCH

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes

(2013) Warren A. Whyte et al.   CELL

Super-Enhancers in the Control of Cell Identity and Disease

(2013) Denes Hnisz et al.   CELL

BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure

(2013) Priti Anand et al.   CELL

BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism

(2013) Daniela Boehm et al.   CELL CYCLE

Inhibition of BET Bromodomain Targets Genetically Diverse Glioblastoma

(2013) Z. Cheng et al.   CLINICAL CANCER RESEARCH

BET bromodomain inhibition suppresses TH17-mediated pathology

(2013) Deanna A. Mele et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Targeting Low-Druggability Bromodomains: Fragment Based Screening and Inhibitor Design against the BAZ2B Bromodomain

(2013) Fleur M. Ferguson et al.   JOURNAL OF MEDICINAL CHEMISTRY

BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms

(2013) B S Wyspiańska et al.   LEUKEMIA

Acetylation of RNA Polymerase II Regulates Growth-Factor-Induced Gene Transcription in Mammalian Cells

(2013) Sebastian Schröder et al.   MOLECULAR CELL

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain

(2013) S. Picaud 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

Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family

(2012) Panagis Filippakopoulos et al.   CELL

Down-regulation of NF-κB Transcriptional Activity in HIV-associated Kidney Disease by BRD4 Inhibition

(2012) Guangtao Zhang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Druggability Analysis and Structural Classification of Bromodomain Acetyl-lysine Binding Sites

(2012) Lewis R. Vidler et al.   JOURNAL OF MEDICINAL CHEMISTRY

Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins

(2012) W. W. Lockwood et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis

(2011) Y. Mishima et al.   BLOOD

A Poised Chromatin Platform for TGF-β Access to Master Regulators

(2011) Qiaoran Xi et al.   CELL

Analysis of the Human Endogenous Coregulator Complexome

(2011) Anna Malovannaya et al.   CELL

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

(2011) Jake E. Delmore et al.   CELL

Identification of 67 Histone Marks and Histone Lysine Crotonylation as a New Type of Histone Modification

(2011) Minjia Tan et al.   CELL

Two-pronged Binding with Bromodomain-containing Protein 4 Liberates Positive Transcription Elongation Factor b from Inactive Ribonucleoprotein Complexes

(2011) Sebastian Schröder et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands

(2011) David S. Hewings et al.   JOURNAL OF MEDICINAL CHEMISTRY

CECR2 Is Involved in Spermatogenesis and Forms a Complex with SNF2H in the Testis

(2011) Peter J. Thompson et al.   JOURNAL OF MOLECULAR BIOLOGY

The Brd4 Extraterminal Domain Confers Transcription Activation Independent of pTEFb by Recruiting Multiple Proteins, Including NSD3

(2011) S. Rahman et al.   MOLECULAR AND CELLULAR BIOLOGY

RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia

(2011) Johannes Zuber et al.   NATURE

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

(2011) Mark A. Dawson et al.   NATURE

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

Regulation of p53: TRIM24 enters the RING

(2010) Abhinav K. Jain et al.   CELL CYCLE

Chromatin remodelling during development

(2010) Lena Ho et al.   NATURE

Suppression of inflammation by a synthetic histone mimic

(2010) Edwige Nicodeme et al.   NATURE

Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b

(2010) Lei Zeng et al.   NATURE

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

PML Nuclear Body Component Sp140 Is a Novel Autoantigen in Primary Biliary Cirrhosis

(2009) Alessandro Granito et al.   AMERICAN JOURNAL OF GASTROENTEROLOGY

The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors

(2009) F. M. Perez-Campo et al.   BLOOD

BRD8 is a potential chemosensitizing target for spindle poisons in colorectal cancer therapy

(2009) Yamada   INTERNATIONAL JOURNAL OF ONCOLOGY

Cooperative binding of two acetylation marks on a histone tail by a single bromodomain

(2009) Jeanne Morinière et al.   NATURE

Molecular Architecture of Quartet MOZ/MORF Histone Acetyltransferase Complexes

(2008) M. Ullah et al.   MOLECULAR AND CELLULAR BIOLOGY

WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity

(2008) Andrew Xiao et al.   NATURE

Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing

(2008) Lei Zeng et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY