Bromodomain inhibitors and cancer therapy: From structures to applications

RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease

(2016) Dean Gilham et al.   ATHEROSCLEROSIS

Modulation of p300/CBP Acetylation of Nucleosomes by Bromodomain Ligand I-CBP112

(2016) Beth E. Zucconi et al.   BIOCHEMISTRY

OTX015 (MK-8628), a novel BET inhibitor, displaysin vitroandin vivoantitumor effects alone and in combination with conventional therapies in glioblastoma models

(2016) Caroline Berenguer-Daizé et al.   INTERNATIONAL JOURNAL OF CANCER

ATAD2 overexpression is associated with progression and prognosis in colorectal cancer

(2016) Mingming Hou et al.   JAPANESE JOURNAL OF CLINICAL ONCOLOGY

CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer

(2016) Mark L. McCleland et al.   JOURNAL OF CLINICAL INVESTIGATION

Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain

(2016) Apirat Chaikuad et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex

(2016) Charlotte L. Sutherell 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

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

Effects of the BET-inhibitor, RVX-208 on the HDL lipidome and glucose metabolism in individuals with prediabetes: A randomized controlled trial

(2016) Andrew L. Siebel et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

(2016) J. Perez-Pena et al.   MOLECULAR CANCER THERAPEUTICS

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer

(2016) Shaokun Shu et al.   NATURE

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

(2016) Anja F Hohmann et al.   Nature Chemical Biology

Fragment-Based Discovery of a Selective and Cell-Active Benzodiazepinone CBP/EP300 Bromodomain Inhibitor (CPI-637)

(2016) Alexander M. Taylor et al.   ACS Medicinal Chemistry Letters

BET Bromodomain Proteins Brd2, Brd3 and Brd4 Selectively Regulate Metabolic Pathways in the Pancreatic β-Cell

(2016) Jude T. Deeney et al.   PLoS One

Effect of the BET Protein Inhibitor, RVX-208, on Progression of Coronary Atherosclerosis: Results of the Phase 2b, Randomized, Double-Blind, Multicenter, ASSURE Trial

(2015) Stephen J. Nicholls et al.   American Journal of Cardiovascular Drugs

Inhibition of BET proteins impairs estrogen-mediated growth and transcription in breast cancers by pausing RNA polymerase advancement

(2015) Surojeet Sengupta et al.   BREAST CANCER RESEARCH AND TREATMENT

KAT6B Is a Tumor Suppressor Histone H3 Lysine 23 Acetyltransferase Undergoing Genomic Loss in Small Cell Lung Cancer

(2015) Laia Simó-Riudalbas et al.   CANCER RESEARCH

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

Protein Lysine Acetylation by p300/CBP

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

Transcriptional Profiling of a Selective CREB Binding Protein Bromodomain Inhibitor Highlights Therapeutic Opportunities

(2015) Eugene L. Piatnitski Chekler et al.   CHEMISTRY & BIOLOGY

ATAD2 is overexpressed in gastric cancer and serves as an independent poor prognostic biomarker

(2015) M.- J. Zhang et al.   Clinical & Translational Oncology

MicroRNA-410 promotes cell proliferation by targeting BRD7 in non-small cell lung cancer

(2015) Dengrui Li et al.   FEBS LETTERS

Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors

(2015) Paul Bamborough 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

Sensitivity of Small Cell Lung Cancer to BET Inhibition Is Mediated by Regulation of ASCL1 Gene Expression

(2015) R. Lenhart et al.   MOLECULAR CANCER THERAPEUTICS

Small Molecule MYC Inhibitor Conjugated to Integrin-Targeted Nanoparticles Extends Survival in a Mouse Model of Disseminated Multiple Myeloma

(2015) D. Soodgupta et al.   MOLECULAR CANCER THERAPEUTICS

EGFR Mutation Promotes Glioblastoma through Epigenome and Transcription Factor Network Remodeling

(2015) Feng Liu et al.   MOLECULAR CELL

Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma

(2015) Pawel K Mazur et al.   NATURE MEDICINE

Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies

(2015) Siu Chiu Chan et al.   NUCLEIC ACIDS RESEARCH

The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models

(2015) P L Garcia et al.   ONCOGENE

Imiquimod-induced psoriasis-like skin inflammation is suppressed by BET bromodomain inhibitor in mice through RORC/IL-17A pathway modulation

(2015) Ahmed Nadeem et al.   PHARMACOLOGICAL RESEARCH

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

Bromodomain and extra-terminal domain bromodomain inhibition prevents synovial inflammation via blocking IκB kinase–dependent NF-κB activation in rheumatoid fibroblast-like synoviocytes

(2015) Youjun Xiao et al.   RHEUMATOLOGY

Overexpression of ANCCA/ATAD2 in endometrial carcinoma and its correlation with tumor progression and poor prognosis

(2015) Pan Shang et al.   TUMOR BIOLOGY

Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma

(2015) Matthew B. Siegel 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

GLI2-dependent c-MYC upregulation mediates resistance of pancreatic cancer cells to the BET bromodomain inhibitor JQ1

(2015) Krishan Kumar et al.   Scientific Reports

Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance

(2015) O. Fedorov et al.   Science Advances

Inhibition of BET bromodomain proteins as a therapeutic approach in prostate cancer.

(2015) Anastasia Wyce et al.   Oncotarget

BET bromodomain protein inhibition is a therapeutic option for medulloblastoma

(2015) Anton George Henssen et al.   Oncotarget

Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma

(2015) Sujatha Venataraman et al.   Oncotarget

Resistance to everolimus driven by epigenetic regulation of MYC in ER+ breast cancers

(2015) Teeru Bihani et al.   Oncotarget

The bromodomain protein inhibitor I-BET151 suppresses expression of inflammatory genes and matrix degrading enzymes in rheumatoid arthritis synovial fibroblasts

(2014) Kerstin Klein et al.   ANNALS OF THE RHEUMATIC DISEASES

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

(2014) Wei-Na Wan et al.   Asian Pacific Journal of Cancer Prevention

I-BET151 selectively regulates IL-6 production

(2014) Elyse Barrett et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Hallmarks of triple negative breast cancer emerging at last?

(2014) Rosa Bernardi et al.   CELL RESEARCH

An epigenomic approach to therapy for tamoxifen-resistant breast cancer

(2014) Qin Feng et al.   CELL RESEARCH

Identification of Structural Features of 2-Alkylidene-1,3-Dicarbonyl Derivatives that Induce Inhibition and/or Activation of Histone Acetyltransferases KAT3B/p300 and KAT2B/PCAF

(2014) Sabrina Castellano et al.   ChemMedChem

The Histone Acetylase Activator Pentadecylidenemalonate 1b Rescues Proliferation and Differentiation in the Human Cardiac Mesenchymal Cells of Type 2 Diabetic Patients

(2014) Matteo Vecellio et al.   DIABETES

BET bromodomain proteins are required for glioblastoma cell proliferation

(2014) Chiara Pastori et al.   Epigenetics

The Epigenetic Regulator I-BET151 Induces BIM-Dependent Apoptosis and Cell Cycle Arrest of Human Melanoma Cells

(2014) Stuart J. Gallagher et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

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

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

Targeting BRG1 Chromatin Remodeler via Its Bromodomain for Enhanced Tumor Cell Radiosensitivity In Vitro and In Vivo

(2014) S.-J. Kwon et al.   MOLECULAR CANCER THERAPEUTICS

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

(2014) Irfan A. Asangani 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

Targeting bromodomains: epigenetic readers of lysine acetylation

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

The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss

(2014) L-H Tsai et al.   ONCOGENE

Control of NF-kB activity in human melanoma by bromodomain and extra-terminal protein inhibitor I-BET151

(2014) Stuart J. Gallagher et al.   Pigment Cell & Melanoma Research

BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma

(2014) Joydeep Bhadury et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells

(2014) Wenxian Fu et al.   eLife

Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762

(2013) A. Chaidos et al.   BLOOD

Discovery and Characterization of Super-Enhancer-Associated Dependencies in Diffuse Large B Cell Lymphoma

(2013) Bjoern Chapuy et al.   CANCER CELL

Histone Acetyltransferase PCAF Is Required for Hedgehog-Gli-Dependent Transcription and Cancer Cell Proliferation

(2013) M. Malatesta et al.   CANCER RESEARCH

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

(2013) S. Picaud et al.   CANCER RESEARCH

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

(2013) Jakob Lovén et al.   CELL

Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non-Small Cell Lung Cancer

(2013) T. Shimamura et al.   CLINICAL CANCER RESEARCH

Tumor Suppressive Effects of Bromodomain-Containing Protein 7 (BRD7) in Epithelial Ovarian Carcinoma

(2013) Young-Ae Park et al.   CLINICAL CANCER RESEARCH

Inhibition of BET Bromodomain Targets Genetically Diverse Glioblastoma

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

BET Bromodomain Inhibition of MYC-Amplified Medulloblastoma

(2013) P. Bandopadhayay et al.   CLINICAL CANCER RESEARCH

Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

(2013) Olivier Mirguet 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

A Novel Activator of CBP/p300 Acetyltransferases Promotes Neurogenesis and Extends Memory Duration in Adult Mice

(2013) S. Chatterjee et al.   JOURNAL OF NEUROSCIENCE

Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia

(2013) M A Dawson et al.   LEUKEMIA

BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms

(2013) B S Wyspiańska et al.   LEUKEMIA

Brd4 maintains constitutively active NF-κB in cancer cells by binding to acetylated RelA

(2013) Z Zou et al.   ONCOGENE

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

Small organic molecules targeting PCAF bromodomain as potent inhibitors of HIV-1 replication

(2013) Qiang Wang et al.   MedChemComm

RVX 208

(2013)   Drugs in research & development

P300/CBP Associated Factor Regulates Nitroglycerin-Dependent Arterial Relaxation by N ε -Lysine Acetylation of Contractile Proteins

(2012) Claudia Colussi et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Cancer and the bromodomains of BAF180

(2012) Peter M. Brownlee et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia

(2012) C. J. Ott et al.   BLOOD

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

(2012) Panagis Filippakopoulos et al.   CELL

Prognostic relevance of BRD7 expression in colorectal carcinoma

(2012) Wen-Jing Wu et al.   EUROPEAN JOURNAL OF CLINICAL INVESTIGATION

The bromodomain interaction module

(2012) Panagis Filippakopoulos et al.   FEBS LETTERS

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

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

p300/CBP-Associated Factor Selectively Regulates the Extinction of Conditioned Fear

(2012) W. Wei et al.   JOURNAL OF NEUROSCIENCE

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

(2012) Martin Peifer et al.   NATURE GENETICS

PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27Kip1

(2012) M. Perez-Luna et al.   NUCLEIC ACIDS RESEARCH

SS18 Together with Animal-Specific Factors Defines Human BAF-Type SWI/SNF Complexes

(2012) Evelien Middeljans et al.   PLoS One

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

Modulation of the activity of histone acetyltransferases by long chain alkylidenemalonates (LoCAMs)

(2011) Ciro Milite 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

The interactions between MicroRNA-200c and BRD7 in endometrial carcinoma

(2011) Young-Ae Park et al.   GYNECOLOGIC ONCOLOGY

Bromodomain-peptide displacement assays for interactome mapping and inhibitor discovery

(2011) Martin Philpott et al.   Molecular BioSystems

Inactivating mutations of acetyltransferase genes in B-cell lymphoma

(2011) Laura Pasqualucci et al.   NATURE

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

Inhibition of p53 acetylation by INHAT subunit SET/TAF-Iβ represses p53 activity

(2011) Ji-Young Kim et al.   NUCLEIC ACIDS RESEARCH

N -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart

(2011) C. Colussi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

BRD7, a Subunit of SWI/SNF Complexes, Binds Directly to BRCA1 and Regulates BRCA1-Dependent Transcription

(2010) M. T. Harte et al.   CANCER RESEARCH

Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor

(2010) Erin M. Bowers et al.   CHEMISTRY & BIOLOGY

The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats

(2010) Claudio Guetg et al.   EMBO JOURNAL

RVX-208

(2010) Dana Bailey et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

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

Androgen-Induced Coactivator ANCCA Mediates Specific Androgen Receptor Signaling in Prostate Cancer

(2009) J. X. Zou et al.   CANCER RESEARCH

ATAD2 Is a Novel Cofactor for MYC, Overexpressed and Amplified in Aggressive Tumors

(2009) M. Ciro et al.   CANCER RESEARCH

An operational definition of epigenetics

(2009) S. L. Berger et al.   GENES & DEVELOPMENT

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

(2009) Jeanne Morinière et al.   NATURE

Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases

(2008) Gianluca Sbardella et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines

(2008) Pedro P. Medina et al.   HUMAN MUTATION

Mechanism of p300 Specific Histone Acetyltransferase Inhibition by Small Molecules

(2008) M. Arif et al.   JOURNAL OF MEDICINAL CHEMISTRY

PCAF Acetylates β-Catenin and Improves Its Stability

(2008) Xinjian Ge et al.   MOLECULAR BIOLOGY OF THE CELL

Epigenetics in Cancer

(2008) Manel Esteller   NEW ENGLAND JOURNAL OF MEDICINE