Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology

Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins

(2016) Brigitt Raux et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor

(2016) Laetitia J. Martin et al.   JOURNAL OF MEDICINAL CHEMISTRY

4-Acyl Pyrrole Derivatives Yield Novel Vectors for Designing Inhibitors of the Acetyl-Lysine Recognition Site of BRD4(1)

(2016) Martin Hügle et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials

(2016) Brian K. Albrecht et al.   JOURNAL OF MEDICINAL CHEMISTRY

NanoBRET—A Novel BRET Platform for the Analysis of Protein–Protein Interactions

(2015) Thomas Machleidt et al.   ACS Chemical Biology

Unexpected Off-Targets and Paradoxical Pathway Activation by Kinase Inhibitors

(2015) Oliver Hantschel   ACS Chemical Biology

Dual Screening of BPTF and Brd4 Using Protein-Observed Fluorine NMR Uncovers New Bromodomain Probe Molecules

(2015) Andrew K. Urick et al.   ACS Chemical Biology

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

(2015) Michael Zengerle 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

Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy

(2015) S. Picaud et al.   CANCER RESEARCH

The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies

(2015) Bhavatarini Vangamudi et al.   CANCER RESEARCH

Discovery of Chemical Inhibitors of Human Bromodomains

(2015) Guangtao Zhang et al.   CHEMICAL REVIEWS

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Binding Mode of Acetylated Histones to Bromodomains: Variations on a Common Motif

(2015) Jean-Rémy Marchand et al.   ChemMedChem

Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors

(2015) Paul Bamborough et al.   JOURNAL OF MEDICINAL CHEMISTRY

New Synthetic Routes to Triazolo-benzodiazepine Analogues: Expanding the Scope of the Bump-and-Hole Approach for Selective Bromo and Extra-Terminal (BET) Bromodomain Inhibition

(2015) Matthias G. J. Baud et al.   JOURNAL OF MEDICINAL CHEMISTRY

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 a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF

(2015) James Bennett 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

Structure-Based Design of γ-Carboline Analogues as Potent and Specific BET Bromodomain Inhibitors

(2015) Xu Ran et al.   JOURNAL OF MEDICINAL CHEMISTRY

Fragment-Based Design of Selective Nanomolar Ligands of the CREBBP Bromodomain

(2015) Andrea Unzue et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of CREBBP Bromodomain Inhibitors by High-Throughput Docking and Hit Optimization Guided by Molecular Dynamics

(2015) Min Xu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Disrupting Acetyl-Lysine Recognition: Progress in the Development of Bromodomain Inhibitors

(2015) F. Anthony Romero et al.   JOURNAL OF MEDICINAL CHEMISTRY

Know your target, know your molecule

(2015) Mark E Bunnage et al.   Nature Chemical Biology

Probing the epigenome

(2015) Andrea Huston et al.   Nature Chemical Biology

The promise and peril of chemical probes

(2015) Cheryl H Arrowsmith et al.   Nature Chemical Biology

CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses

(2015) Ariane Hammitzsch et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

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

A Subset of Human Bromodomains Recognizes Butyryllysine and Crotonyllysine Histone Peptide Modifications

(2015) E. Megan Flynn et al.   STRUCTURE

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

(2015) Duncan A. Hay et al.   MedChemComm

BRD4 Structure–Activity Relationships of Dual PLK1 Kinase/BRD4 Bromodomain Inhibitor BI-2536

(2015) Lijia Chen et al.   ACS Medicinal Chemistry Letters

Target engagement and drug residence time can be observed in living cells with BRET

(2015) Matthew B. Robers et al.   Nature Communications

Inhibition of BET bromodomains as a therapeutic strategy for cancer drug discovery

(2015) Lei-lei Fu et al.   Oncotarget

BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells

(2015) Marie-Magdelaine Coudé et al.   Oncotarget

Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo

(2015) J M Gajer et al.   Oncogenesis

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

Small Molecule Inhibitors of Bromodomain–Acetyl-lysine Interactions

(2014) Michael Brand et al.   ACS Chemical Biology

A Series of Potent CREBBP Bromodomain Ligands Reveals an Induced-Fit Pocket Stabilized by a Cation-π Interaction

(2014) Timothy P. C. Rooney et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The bromodomain: From epigenome reader to druggable target

(2014) Roberto Sanchez et al.   Biochimica et Biophysica Acta-Gene Regulatory Mechanisms

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

(2014) Jian Shi et al.   CANCER CELL

Privileged Diazepine Compounds and Their Emergence as Bromodomain Inhibitors

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

Nonequivalent Response to Bromodomain-Targeting BET Inhibitors in Oligodendrocyte Cell Fate Decision

(2014) Cheng-Ming Chiang   CHEMISTRY & BIOLOGY

Selective Chemical Modulation of Gene Transcription Favors Oligodendrocyte Lineage Progression

(2014) Mar Gacias et al.   CHEMISTRY & BIOLOGY

Bromodomains and Their Pharmacological Inhibitors

(2014) Daniel Gallenkamp et al.   ChemMedChem

Phenotypic screening and fragment-based approaches to the discovery of small-molecule bromodomain ligands

(2014) Laura E Jennings et al.   Future Medicinal Chemistry

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

Biased Multicomponent Reactions to Develop Novel Bromodomain Inhibitors

(2014) Michael R McKeown et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Optimization of Small-Molecule Ligands for the CBP/p300 Bromodomains

(2014) Duncan A. Hay et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition

(2014) Junwei Shi et al.   MOLECULAR CELL

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

(2014) Pietro Ciceri et al.   Nature Chemical Biology

Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders

(2014) Katrina J. Falkenberg et al.   NATURE REVIEWS DRUG DISCOVERY

Targeting bromodomains: epigenetic readers of lysine acetylation

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

RVX-208, an Inducer of ApoA-I in Humans, Is a BET Bromodomain Antagonist

(2014) Kevin G. McLure et al.   PLoS One

The new frontier of genome engineering with CRISPR-Cas9

(2014) J. A. Doudna et al.   SCIENCE

Tracking cancer drugs in living cells by thermal profiling of the proteome

(2014) M. M. Savitski et al.   SCIENCE

A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes

(2014) M. G. J. Baud et al.   SCIENCE

Structure-based approaches towards identification of fragments for the low-druggability ATAD2 bromodomain

(2014) Apirat Chaikuad et al.   MedChemComm

Evaluation of functional groups as acetyl-lysine mimetics for BET bromodomain inhibition

(2014) Phillip P. Sharp et al.   MedChemComm

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

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

The Commonly Used PI3-Kinase Probe LY294002 Is an Inhibitor of BET Bromodomains

(2013) Antje Dittmann et al.   ACS Chemical Biology

Cyclin-Dependent Kinase Inhibitor Dinaciclib Interacts with the Acetyl-Lysine Recognition Site of Bromodomains

(2013) Mathew P. Martin et al.   ACS Chemical Biology

4-Acyl Pyrroles: Mimicking Acetylated Lysines in Histone Code Reading

(2013) Xavier Lucas et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Readout of Epigenetic Modifications

(2013) Dinshaw J. Patel et al.   Annual Review of Biochemistry

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

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

[1,2,4]Triazolo[4,3-a]phthalazines: Inhibitors of Diverse Bromodomains

(2013) Oleg Fedorov et al.   JOURNAL OF MEDICINAL CHEMISTRY

Optimization of 3,5-Dimethylisoxazole Derivatives as Potent Bromodomain Ligands

(2013) David S. Hewings et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Guided Design of Potent Diazobenzene Inhibitors for the BET Bromodomains

(2013) Guangtao Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Genome-wide localization of small molecules

(2013) Lars Anders et al.   NATURE BIOTECHNOLOGY

Target validation using chemical probes

(2013) Mark E Bunnage et al.   Nature Chemical Biology

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

Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay

(2013) D. M. Molina et al.   SCIENCE

Structural Insights into Acetylated-Histone H4 Recognition by the Bromodomain-PHD Finger Module of Human Transcriptional Coactivator CBP

(2013) Alexander N. Plotnikov et al.   STRUCTURE

Cancer Epigenetics: From Mechanism to Therapy

(2012) Mark A. Dawson et al.   CELL

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

(2012) Panagis Filippakopoulos et al.   CELL

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

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

Progress in the Development and Application of Small Molecule Inhibitors of Bromodomain–Acetyl-lysine Interactions

(2012) David S. Hewings et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

Epigenetic protein families: a new frontier for drug discovery

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

BRD4 is an atypical kinase that phosphorylates Serine2 of the RNA Polymerase II carboxy-terminal domain

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

Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family

(2011) Panagis Filippakopoulos et al.   BIOORGANIC & MEDICINAL CHEMISTRY

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

(2011) Jake E. Delmore et al.   CELL

A Small Molecule Binding to the Coactivator CREB-Binding Protein Blocks Apoptosis in Cardiomyocytes

(2011) Jagat C. Borah et al.   CHEMISTRY & BIOLOGY

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

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

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

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

Fragment-Based Discovery of Bromodomain Inhibitors Part 1: Inhibitor Binding Modes and Implications for Lead Discovery

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

Rational Design of Cyclic Peptide Modulators of the Transcriptional Coactivator CBP: A New Class of p53 Inhibitors

(2011) Guillermo Gerona-Navarro et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Structural Basis and Specificity of Acetylated Transcription Factor GATA1 Recognition by BET Family Bromodomain Protein Brd3

(2011) R. Gamsjaeger et al.   MOLECULAR AND CELLULAR BIOLOGY

Bromodomain-peptide displacement assays for interactome mapping and inhibitor discovery

(2011) Martin Philpott et al.   Molecular BioSystems

Bromodomain protein Brd3 associates with acetylated GATA1 to promote its chromatin occupancy at erythroid target genes

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

Probing the Probes: Fitness Factors For Small Molecule Tools

(2010) Paul Workman et al.   CHEMISTRY & BIOLOGY

Privileged scaffolds for library design and drug discovery

(2010) Matthew E Welsch et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

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

The art of the chemical probe

(2010) Stephen V Frye   Nature Chemical Biology

Guidelines for the effective use of chemical inhibitors of protein function to understand their roles in cell regulation: Table 1

(2009) Philip Cohen   BIOCHEMICAL JOURNAL

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

(2009) Jeanne Morinière et al.   NATURE

The Double Bromodomain Proteins Brd2 and Brd3 Couple Histone Acetylation to Transcription

(2008) Gary LeRoy et al.   MOLECULAR CELL

Lysine Acetylation: Codified Crosstalk with Other Posttranslational Modifications

(2008) Xiang-Jiao Yang et al.   MOLECULAR CELL