A comprehensive review of BET-targeting PROTACs for cancer therapy

Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications

(2022) Nathaniel J. Henning et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

PROTAC targeted protein degraders: the past is prologue

(2022) Miklós Békés et al.   NATURE REVIEWS DRUG DISCOVERY

Targeting epigenetic modulators using PROTAC degraders: Current status and future perspective

(2022) Thomas Webb et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Adjusted degradation of BRD4 S and BRD4 L based on fine structural modifications of the pyrrolopyridone scaffold

(2022) Jingjing Chen et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

The state of the art of PROTAC technologies for drug discovery

(2022) Chao Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A platform for the rapid synthesis of proteolysis targeting chimeras (Rapid-TAC) under miniaturized conditions

(2022) Le Guo et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Clinical considerations for the design of PROTACs in cancer

(2022) Cristina Nieto-Jiménez et al.   Molecular Cancer

Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 1: Exploration of Antibody Linker, Payload Loading, and Payload Molecular Properties

(2021) Peter S. Dragovich et al.   JOURNAL OF MEDICINAL CHEMISTRY

Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy

(2021) Peter S. Dragovich et al.   JOURNAL OF MEDICINAL CHEMISTRY

Frontiers in PROTACs

(2021) Gregory R. Hughes et al.   DRUG DISCOVERY TODAY

Nimbolide, a Neem Limonoid, Is a Promising Candidate for the Anticancer Drug Arsenal

(2021) Siddavaram Nagini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cancer Selective Target Degradation by Folate-Caged PROTACs

(2021) Jing Liu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Aptamer‐PROTAC Conjugates (APCs) for Tumor‐Specific Targeting in Breast Cancer

(2021) Shipeng He et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Structural insights into SMCR8 C-degron recognition by FEM1B

(2021) Shidong Zhao et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Bromodomains: A novel target for the anticancer therapy

(2021) Shivani Gokani et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Protein degradation technology: a strategic paradigm shift in drug discovery

(2021) Haobin Li et al.   Journal of Hematology & Oncology

Harnessing the E3 Ligase KEAP1 for Targeted Protein Degradation

(2021) Jieli Wei et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Stromal induction of BRD4 phosphorylation Results in Chromatin Remodeling and BET inhibitor Resistance in Colorectal Cancer

(2021) Wenyu Wang et al.   Nature Communications

E3 Ligase Ligands in Successful PROTACs: An Overview of Syntheses and Linker Attachment Points

(2021) Aleša Bricelj et al.   Frontiers in Chemistry

Opportunities and Challenges of Small Molecule Induced Targeted Protein Degradation

(2021) Ming He et al.   Frontiers in Cell and Developmental Biology

Phenyl‐Glutarimides: Alternative Cereblon Binders for the Design of PROTACs

(2021) Jaeki Min et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Design, Synthesis, and Evaluation of Trivalent PROTACs Having a Functionalization Site with Controlled Orientation

(2021) Yifan Huang et al.   BIOCONJUGATE CHEMISTRY

Structural basis and regulation of the reductive stress response

(2021) Andrew G. Manford et al.   CELL

Identification of a selective BRD4 PROTAC with potent antiproliferative effects in AR-positive prostate cancer based on a dual BET/PLK1 inhibitor

(2021) Rong Hu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Development of photocontrolled BRD4 PROTACs for tongue squamous cell carcinoma (TSCC)

(2021) Zhenzhen Li et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Developments of CRBN-based PROTACs as potential therapeutic agents

(2021) Chao Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Amide-to-Ester Substitution as a Strategy for Optimizing PROTAC Permeability and Cellular Activity

(2021) Victoria G. Klein et al.   JOURNAL OF MEDICINAL CHEMISTRY

The role of distinct BRD4 isoforms and their contribution to high-grade serous ovarian carcinoma pathogenesis

(2021) Ana Luiza Drumond-Bock et al.   Molecular Cancer

Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

(2021) Satomi Imaide et al.   Nature Chemical Biology

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

(2020) George M. Burslem et al.   CELL

Optical Control of Small Molecule-Induced Protein Degradation

(2020) Yuta Naro et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

(2020) Emily J. Faivre et al.   NATURE

Make your best BET: The emerging role of BET inhibitor treatment in malignant tumors

(2020) Oliver Bechter et al.   PHARMACOLOGY & THERAPEUTICS

Light-induced control of protein destruction by opto-PROTAC

(2020) Jing Liu et al.   Science Advances

PHOTACs enable optical control of protein degradation

(2020) Martin Reynders et al.   Science Advances

Design, synthesis, and biological evaluation of 4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine derivatives as novel dual-PLK1/BRD4 inhibitors

(2020) Ning-Yu Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Novel strategies targeting bromodomain-containing protein 4 (BRD4) for cancer drug discovery

(2020) Dailin Liang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of N-Ethyl-4-[2-(4-fluoro-2,6-dimethyl-phenoxy)-5-(1-hydroxy-1-methyl-ethyl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (ABBV-744), a BET Bromodomain Inhibitor with Selectivity for the Second Bromodomain

(2020) George S. Sheppard et al.   JOURNAL OF MEDICINAL CHEMISTRY

Opposing Functions of BRD4 Isoforms in Breast Cancer

(2020) Shwu-Yuan Wu et al.   MOLECULAR CELL

PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics

(2020) Sajid Khan et al.   ONCOGENE

Development of small-molecule BRD4 degraders based on pyrrolopyridone derivative

(2020) Jian Zhang et al.   BIOORGANIC CHEMISTRY

CDDO-Imidazolide Targets Multiple Amino Acid Residues on the Nrf2 Adaptor, Keap1

(2020) Xiaoli Meng et al.   JOURNAL OF MEDICINAL CHEMISTRY

MDM2 inhibition: an important step forward in cancer therapy

(2020) Marina Konopleva et al.   LEUKEMIA

A Cellular Mechanism to Detect and Alleviate Reductive Stress

(2020) Andrew G. Manford et al.   CELL

PROTAC: A promising technology for cancer treatment

(2020) Xin Zhou et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Bardoxolone conjugation enables targeted protein degradation of BRD4

(2020) Bingqi Tong et al.   Scientific Reports

Recent advances in small molecule PROTACs for the treatment of cancer

(2020) Wen Li et al.   CURRENT MEDICINAL CHEMISTRY

Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges

(2020) Shenxin Zeng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

The KEAP1–NRF2 System as a Molecular Target of Cancer Treatment

(2020) Keiko Taguchi et al.   Cancers

A novel cereblon modulator for targeted protein degradation

(2019) Sung Ah Kim et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structure–Activity and Structure–Conformation Relationships of Aryl Propionic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1/Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1/NRF2) Protein–Protein Interaction

(2019) Tom D. Heightman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Acquired Resistance to BET-PROTACs(Proteolysis Targeting Chimeras) Caused by Genomic Alterations in Core Components of E3 ligase Complexes

(2019) Lu Zhang et al.   MOLECULAR CANCER THERAPEUTICS

Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction

(2019) Xing Qiu et al.   ORGANIC LETTERS

Bromodomain-Containing Protein 4: A Druggable Target

(2019) Yingying Shi et al.   CURRENT DRUG TARGETS

Harnessing the anti-cancer natural product nimbolide for targeted protein degradation

(2019) Jessica N. Spradlin et al.   Nature Chemical Biology

Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16

(2019) Xiaoyu Zhang et al.   Nature Chemical Biology

Bromodomains: a new target class for drug development

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

Molecular mechanisms of cereblon-based drugs

(2019) Tomoko Asatsuma-Okumura et al.   PHARMACOLOGY & THERAPEUTICS

Reversible Spatiotemporal Control of Induced Protein Degradation by Bistable PhotoPROTACs

(2019) Patrick Pfaff et al.   ACS Central Science

Antibody Conjugation of a Chimeric BET Degrader Enables in vivo Activity

(2019) Thomas H. Pillow et al.   ChemMedChem

Light-Induced Protein Degradation with Photocaged PROTACs

(2019) Gang Xue et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeting MDM2 for novel molecular therapy: Beyond oncology

(2019) Wei Wang et al.   MEDICINAL RESEARCH REVIEWS

Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15

(2019) Tyler B. Faust et al.   Nature Chemical Biology

Structural Basis and Kinetic Pathway of RBM39 Recruitment to DCAF15 by a Sulfonamide Molecular Glue E7820

(2019) Xinlin Du et al.   STRUCTURE

Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15

(2019) Tabitha C. Ting et al.   Cell Reports

Structure-Based Design of a Macrocyclic PROTAC

(2019) Andrea Testa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A patent review of BRD4 inhibitors (2013-2019)

(2019) Tian Lu et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex

(2019) Dirksen E. Bussiere et al.   Nature Chemical Biology

Final results of a phase 2, open-label study of indisulam, idarubicin, and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome

(2018) Rita Assi et al.   CANCER

Discovery of a Keap1-dependent peptide PROTAC to knockdown Tau by ubiquitination-proteasome degradation pathway

(2018) Mengchen Lu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

(2018) Chong Qin et al.   JOURNAL OF MEDICINAL CHEMISTRY

3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein Degradation

(2018) Andrea Testa et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Plasticity in binding confers selectivity in ligand-induced protein degradation

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

DUB3 Promotes BET Inhibitor Resistance and Cancer Progression by Deubiquitinating BRD4

(2018) Xin Jin et al.   MOLECULAR CELL

MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53

(2018) John Hines et al.   CANCER RESEARCH

BRD4 and Cancer: going beyond transcriptional regulation

(2018) Benedetta Donati et al.   Molecular Cancer

A “Click Chemistry Platform” for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation

(2017) Ryan P. Wurz et al.   JOURNAL OF MEDICINAL CHEMISTRY

Impact of Target Warhead and Linkage Vector on Inducing Protein Degradation: Comparison of Bromodomain and Extra-Terminal (BET) Degraders Derived from Triazolodiazepine (JQ1) and Tetrahydroquinoline (I-BET726) BET Inhibitor Scaffolds

(2017) Kwok-Ho Chan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Drug Discovery Targeting Bromodomain-Containing Protein 4

(2017) Zhiqing Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones?

(2017) Ian Churcher   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression

(2017) Bing Zhou et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural basis of PROTAC cooperative recognition for selective protein degradation

(2017) Morgan S Gadd et al.   Nature Chemical Biology

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

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

(2017) Ting Han et al.   SCIENCE

The KEAP1–NRF2 System in Cancer

(2017) Keiko Taguchi et al.   Frontiers in Oncology

Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery

(2016) Thomas G. Davies et al.   JOURNAL OF MEDICINAL CHEMISTRY

A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase

(2016) Mary E. Matyskiela et al.   NATURE

Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase

(2016) Georg Petzold et al.   NATURE

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

PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

(2016) Kanak Raina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition

(2016) Julianty Frost et al.   Nature Communications

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

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

Protein Degradation by In-Cell Self-Assembly of Proteolysis Targeting Chimeras

(2016) Honorine Lebraud et al.   ACS Central Science

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS

(2015) Jan Krönke et al.   NATURE

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

Structure-Guided Design and Optimization of Small Molecules Targeting the Protein–Protein Interaction between the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities

(2014) Carles Galdeano et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide

(2014) Eric S. Fischer et al.   NATURE

Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs

(2014) Philip P Chamberlain et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Targeting the von Hippel–Lindau E3 Ubiquitin Ligase Using Small Molecules To Disrupt the VHL/HIF-1α Interaction

(2012) Dennis L. Buckley et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Phase I Study of E7820, an Oral Inhibitor of Integrin  -2 Expression with Antiangiogenic Properties, in Patients with Advanced Malignancies

(2011) M. Mita et al.   CLINICAL CANCER RESEARCH

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

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

(2009) Jeanne Morinière et al.   NATURE