Achieving clinical success with BET inhibitors as anti-cancer agents

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

(2020) Emily J. Faivre et al.   NATURE

Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer

(2020) Shaokun Shu et al.   MOLECULAR CELL

Selective targeting of BD1 and BD2 of the BET proteins in cancer and immuno-inflammation

(2020) Omer Gilan et al.   SCIENCE

Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors

(2020) Johanna M. Schafer et al.   Science Translational Medicine

Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma

(2020) V. Moreno et al.   ANNALS OF ONCOLOGY

Bromodomain-selective BET inhibitors are potent antitumor agents against MYC-driven pediatric cancer

(2020) P. Jake Slavish et al.   CANCER RESEARCH

A Phase 1b/2a Study of the Pan-BET Bromodomain Inhibitor ZEN-3694 in Combination with Enzalutamide in Patients with Metastatic Castration Resistant Prostate Cancer

(2020) Rahul R. Aggarwal et al.   CLINICAL CANCER RESEARCH

BET inhibitors synergize with venetoclax to induce apoptosis in MYC-driven lymphomas with high BCL-2 expression

(2020) Thomas E. C. Cummin et al.   Blood Advances

Reprogramming of nucleotide metabolism mediates synergy between epigenetic therapy and MAP Kinase inhibition

(2020) Tatiana Shorstova et al.   MOLECULAR CANCER THERAPEUTICS

Targeting the IGF1R/PI3K/AKT pathway sensitizes Ewing sarcoma to BET bromodomain inhibitors

(2019) Sudan N Loganathan et al.   MOLECULAR CANCER THERAPEUTICS

First-in-human phase I study of the bromodomain and extraterminal motif inhibitor BAY 1238097: emerging pharmacokinetic/pharmacodynamic relationship and early termination due to unexpected toxicity

(2019) Sophie Postel-Vinay et al.   EUROPEAN JOURNAL OF CANCER

SWI/SNF-compromised cancers are susceptible to bromodomain inhibitors

(2019) Tatiana Shorstova et al.   CANCER RESEARCH

Inhibition of BRD4 suppresses the malignancy of breast cancer cells via regulation of Snail

(2019) Linlin Lu et al.   CELL DEATH AND DIFFERENTIATION

Vitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer

(2019) Sushmita Mustafi et al.   EBioMedicine

The BET inhibitor JQ1 attenuates double-strand break repair and sensitizes models of pancreatic ductal adenocarcinoma to PARP inhibitors

(2019) Aubrey L. Miller et al.   EBioMedicine

Bromodomains: a new target class for drug development

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

Apabetalone (RVX-208) reduces vascular inflammation in vitro and in CVD patients by a BET-dependent epigenetic mechanism

(2019) Laura M. Tsujikawa et al.   Clinical Epigenetics

First-in-Human Study of Mivebresib (ABBV-075), an Oral Pan-Inhibitor of Bromodomain and Extra Terminal Proteins, in Patients with Relapsed/Refractory Solid Tumors

(2019) Sarina A. Piha-Paul et al.   CLINICAL CANCER RESEARCH

Acquired Resistance Is Oncogene and Drug Agnostic

(2019) Robert C. Doebele   CANCER CELL

Bromodomain biology and drug discovery

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

AZD5153, a novel BRD4 inhibitor, suppresses human thyroid carcinoma cell growth in vitro and in vivo

(2018) Kun Xu et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

BRD4 Inhibition Is Synthetic Lethal with PARP Inhibitors through the Induction of Homologous Recombination Deficiency

(2018) Chaoyang Sun et al.   CANCER CELL

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

Anti-leukemic efficacy of BET inhibitor in a preclinical mouse model of MLL-AF4+ infant ALL

(2018) Michela Bardini et al.   MOLECULAR CANCER THERAPEUTICS

Genetic modifiers of the BRD4-NUT dependency of NUT midline carcinoma uncovers a synergism between BETis and CDK4/6is

(2018) Sida Liao et al.   GENES & DEVELOPMENT

Potent Activity of the Bromodomain Inhibitor OTX015 in Multiple Myeloma

(2018) Jixiang Shi et al.   MOLECULAR PHARMACEUTICS

Resistance to Epigenetic-Targeted Therapy Engenders Tumor Cell Vulnerabilities Associated with Enhancer Remodeling

(2018) Amanda Balboni Iniguez et al.   CANCER CELL

NUT Carcinoma: Clinicopathologic features, pathogenesis, and treatment

(2018) Christopher A. French   PATHOLOGY INTERNATIONAL

The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2

(2017) Torsten Hartwig et al.   MOLECULAR CELL

Prostate cancer–associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4

(2017) Xiangpeng Dai et al.   NATURE MEDICINE

Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT–mTORC1 activation

(2017) Pingzhao Zhang et al.   NATURE MEDICINE

Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors

(2017) Hana Janouskova et al.   NATURE MEDICINE

BET Bromodomain Inhibition Synergizes with PARP Inhibitor in Epithelial Ovarian Cancer

(2017) Sergey Karakashev et al.   Cell Reports

KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer

(2017) Andrew M. Waters et al.   Cold Spring Harbor Perspectives in Medicine

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

A phenotypic drug discovery study on thienodiazepine derivatives as inhibitors of T cell proliferation induced by CD28 co-stimulation leads to the discovery of a first bromodomain inhibitor

(2016) Junichi Endo et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance

(2016) Richard Marcotte et al.   CELL

The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects

(2016) J. Shahbazi et al.   CLINICAL CANCER RESEARCH

The MAPK Pathway Regulates Intrinsic Resistance to BET Inhibitors in Colorectal Cancer

(2016) Yufang Ma et al.   CLINICAL CANCER RESEARCH

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

Promising in vivo efficacy of the BET bromodomain inhibitor OTX015/MK-8628 in malignant pleural mesothelioma xenografts

(2016) Ramiro Vázquez et al.   INTERNATIONAL JOURNAL OF CANCER

The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition

(2016) Goro Sashida et al.   JOURNAL OF EXPERIMENTAL MEDICINE

HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues

(2016) Xiaoyu Lin et al.   MOLECULAR CANCER THERAPEUTICS

AZD5153: A Novel Bivalent BET Bromodomain Inhibitor Highly Active against Hematologic Malignancies

(2016) G. W. Rhyasen et al.   MOLECULAR CANCER THERAPEUTICS

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

(2016) Shaokun Shu et al.   NATURE

Design and characterization of bivalent BET inhibitors

(2016) Minoru Tanaka et al.   Nature Chemical Biology

Inhibition of BET bromodomain-dependent XIAP and FLIP expression sensitizes KRAS-mutated NSCLC to pro-apoptotic agents

(2016) Olaf Klingbeil et al.   Cell Death & Disease

Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628

(2016) A. Stathis et al.   Cancer Discovery

BET Bromodomain Inhibition Releases the Mediator Complex from Select cis -Regulatory Elements

(2016) Anand S. Bhagwat et al.   Cell Reports

Resistance to BET Bromodomain Inhibitors Is Mediated by Kinome Reprogramming in Ovarian Cancer

(2016) Alison M. Kurimchak et al.   Cell Reports

Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study

(2016) Céline Berthon et al.   Lancet Haematology

Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study

(2016) Sandy Amorim et al.   Lancet Haematology

Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib

(2015) B. Sun et al.   BLOOD

Kinase and BET Inhibitors Together Clamp Inhibition of PI3K Signaling and Overcome Resistance to Therapy

(2015) Elias E. Stratikopoulos et al.   CANCER CELL

The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs

(2015) M. Boi et al.   CLINICAL CANCER RESEARCH

Targeting MYCN-Driven Transcription By BET-Bromodomain Inhibition

(2015) A. Henssen et al.   CLINICAL CANCER RESEARCH

Phase I Population Pharmacokinetic Assessment of the Oral Bromodomain Inhibitor OTX015 in Patients with Haematologic Malignancies

(2015) Elodie Odore et al.   CLINICAL PHARMACOKINETICS

An evaluation of RVX-208 for the treatment of atherosclerosis

(2015) Dragana Nikolic et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis

(2015) Yuan Hu et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

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

Transcriptional plasticity promotes primary and acquired resistance to BET inhibition

(2015) Philipp Rathert et al.   NATURE

BET inhibitor resistance emerges from leukaemia stem cells

(2015) Chun Yew Fong et al.   NATURE

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

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

(2015) P L Garcia et al.   ONCOGENE

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

(2015) Anastasia Wyce et al.   Oncotarget

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

(2014) Jian Shi et al.   CANCER CELL

Small Molecule Control of Chromatin Remodeling

(2014) Aidan Finley et al.   CHEMISTRY & BIOLOGY

Affinity Map of Bromodomain Protein 4 (BRD4) Interactions with the Histone H4 Tail and the Small Molecule Inhibitor JQ1

(2014) Marie Jung et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

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

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

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

An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma

(2014) Maria Giuseppina Baratta et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

(2014) M. G. J. Baud et al.   SCIENCE

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

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

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

Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation

(2013) J. Shi et al.   GENES & DEVELOPMENT

BET Protein Function Is Required for Inflammation: Brd2 Genetic Disruption and BET Inhibitor JQ1 Impair Mouse Macrophage Inflammatory Responses

(2013) A. C. Belkina et al.   JOURNAL OF IMMUNOLOGY

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

Regulation of NO Synthesis, Local Inflammation, and Innate Immunity to Pathogens by BET Family Proteins

(2013) S. Wienerroither et al.   MOLECULAR AND CELLULAR BIOLOGY

MYC, a downstream target of BRD-NUT, is necessary and sufficient for the blockade of differentiation in NUT midline carcinoma

(2013) A R Grayson 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

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

Identification of a novel series of BET family bromodomain inhibitors: Binding mode and profile of I-BET151 (GSK1210151A)

(2012) Jonathan Seal et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Small-Molecule Inhibition of BRDT for Male Contraception

(2012) Martin M. Matzuk et al.   CELL

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

Comprehensive molecular portraits of human breast tumours

(2012) Daniel C. Koboldt et al.   NATURE

Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer

(2012) Christopher E Barbieri et al.   NATURE GENETICS

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

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

(2011) Jake E. Delmore et al.   CELL

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Efficacy and Safety of a Novel Oral Inducer of Apolipoprotein A-I Synthesis in Statin-Treated Patients With Stable Coronary Artery Disease

(2011) Stephen J. Nicholls et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

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

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

PIK3CAMutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer

(2009) Shuji Ogino et al.   JOURNAL OF CLINICAL ONCOLOGY

The Bromodomain Protein Brd4 Stimulates G1Gene Transcription and Promotes Progression to S Phase

(2008) Kazuki Mochizuki et al.   JOURNAL OF BIOLOGICAL CHEMISTRY