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

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

Improved translation of stability for conjugated antibodies using an in vitro whole blood assay

(2020) Aimee Fourie-O’Donohue et al.   mAbs

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

(2020) Emily J. Faivre et al.   NATURE

Antibody–PROTAC Conjugates Enable HER2-Dependent Targeted Protein Degradation of BRD4

(2020) Marı́a Maneiro et al.   ACS Chemical Biology

First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI).

(2020) Daniel Peter Petrylak et al.   JOURNAL OF CLINICAL ONCOLOGY

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

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

(2020) Omer Gilan et al.   SCIENCE

A Facile Synthesis of Ligands for the von Hippel–Lindau E3 Ligase

(2020) Michael Gütschow et al.   SYNTHESIS-STUTTGART

Optimising proteolysis-targeting chimeras (PROTACs) for oral drug delivery: a drug metabolism and pharmacokinetics perspective

(2020) Andy Pike et al.   DRUG DISCOVERY TODAY

The Design and Synthesis of a Highly Selective and In Vivo Capable Inhibitor of the Second Bromodomain (BD2) of the Bromodomain and Extra Terminal Domain (BET) Family of Proteins

(2020) Alex Preston et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Optimisation of a Novel, Weak Bromo and Extra Terminal Domain (BET) Bromodomain Fragment Ligand to a Potent and Selective Second Bromodomain (BD2) Inhibitor

(2020) Jonathan Thomas Seal et al.   JOURNAL OF MEDICINAL CHEMISTRY

GSK789: A Selective Inhibitor of the First Bromodomains (BD1) of the Bromo and Extra Terminal Domain (BET) Proteins

(2020) Robert J. Watson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Design of a Bromodomain and Extraterminal Domain (BET) Inhibitor Selective for the N-Terminal Bromodomains That Retains an Anti-inflammatory and Antiproliferative Phenotype

(2020) Christopher R. Wellaway et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer

(2019) Xin Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase

(2019) Blake E. Smith et al.   Nature Communications

A chemical approach for global protein knockdown from mice to non-human primates

(2019) Xiuyun Sun et al.   Cell Discovery

Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions

(2019) Johannes Popow et al.   JOURNAL OF MEDICINAL CHEMISTRY

SPR-Measured Dissociation Kinetics of PROTAC Ternary Complexes Influence Target Degradation Rate

(2019) Michael J. Roy et al.   ACS Chemical Biology

Proteolysis targeting chimeras (PROTACs) in ‘beyond rule-of-five’ chemical space: Recent progress and future challenges

(2019) Scott D. Edmondson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A Novel Anti-HER2 Antibody-Drug Conjugate XMT-1522 for HER2-Positive Breast And Gastric Cancers Resistant to Trastuzumab Emtansine

(2019) Vadim Le Joncour et al.   MOLECULAR CANCER THERAPEUTICS

BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

(2019) William Farnaby et al.   Nature Chemical Biology

Peptide-Cleavable Self-immolative Maytansinoid Antibody–Drug Conjugates Designed To Provide Improved Bystander Killing

(2019) Juliet A. Costoplus et al.   ACS Medicinal Chemistry Letters

Antibody Conjugation of a Chimeric BET Degrader Enables in vivo Activity

(2019) Thomas H. Pillow et al.   ChemMedChem

Targeted protein degradation: expanding the toolbox

(2019) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

Antibody-mediated delivery of chimeric protein degraders which target estrogen receptor alpha (ERα)

(2019) Peter S. Dragovich et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

High-Throughput Cysteine Scanning To Identify Stable Antibody Conjugation Sites for Maleimide- and Disulfide-Based Linkers

(2018) Rachana Ohri et al.   BIOCONJUGATE CHEMISTRY

Development of Anti-CD74 Antibody–Drug Conjugates to Target Glucocorticoids to Immune Cells

(2018) Philip E. Brandish et al.   BIOCONJUGATE CHEMISTRY

Conjugation of Indoles to Antibodies through a Novel Self-Immolating Linker

(2018) Peter S. Dragovich et al.   CHEMISTRY-A EUROPEAN JOURNAL

An Anti-CLL-1 Antibody-Drug Conjugate for the Treatment of Acute Myeloid Leukemia

(2018) Bing Zheng et al.   CLINICAL CANCER RESEARCH

Targeting STEAP1 Protein in Human Cancer: Current Trends and Future Challenges

(2018) J. Barroca-Ferreira et al.   CURRENT CANCER DRUG TARGETS

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

Glucuronide-linked antibody-tubulysin conjugates display activity in MDR+ and heterogeneous tumor models

(2018) Patrick J. Burke et al.   MOLECULAR CANCER THERAPEUTICS

Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs

(2018) Michael D. Shultz   JOURNAL OF MEDICINAL CHEMISTRY

Preclinical pharmacokinetics and pharmacodynamics of DCLL9718A: An antibody-drug conjugate for the treatment of acute myeloid leukemia

(2018) Douglas D. Leipold et al.   mAbs

Targeted delivery of cytotoxic NAMPT inhibitors using antibody-drug conjugates

(2018) Christopher S Neumann et al.   MOLECULAR CANCER THERAPEUTICS

Targeting Brd4 for cancer therapy: inhibitors and degraders

(2018) Yingchao Duan et al.   MedChemComm

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

(2018) John Hines et al.   CANCER RESEARCH

In VivoKnockdown of Pathogenic Proteins via Specific and Nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent Protein Erasers (SNIPERs)

(2017) Nobumichi Ohoka et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Peptidomimetic Antibody–Drug Conjugate Linkers with Enhanced Protease Specificity

(2017) BinQing Wei 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

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

Modulating Therapeutic Activity and Toxicity of Pyrrolobenzodiazepine Antibody–Drug Conjugates with Self-Immolative Disulfide Linkers

(2017) Thomas H. Pillow et al.   MOLECULAR CANCER THERAPEUTICS

BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment

(2017) Georg E. Winter et al.   MOLECULAR CELL

Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy

(2017) Hao Chen et al.   MOLECULES

Structural basis of PROTAC cooperative recognition for selective protein degradation

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

Strategies and challenges for the next generation of antibody–drug conjugates

(2017) Alain Beck et al.   NATURE REVIEWS DRUG DISCOVERY

Decoupling stability and release in disulfide bonds with antibody-small molecule conjugates

(2017) Thomas H. Pillow et al.   Chemical Science

The Methylene Alkoxy Carbamate Self-Immolative Unit: Utilization for the Targeted Delivery of Alcohol-Containing Payloads with Antibody-Drug Conjugates

(2016) Robert V. Kolakowski et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Novel Phosphate Modified Cathepsin B Linkers: Improving Aqueous Solubility and Enhancing Payload Scope of ADCs

(2016) Jeffrey C. Kern et al.   BIOCONJUGATE CHEMISTRY

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

Intracellular Released Payload Influences Potency and Bystander-Killing Effects of Antibody-Drug Conjugates in Preclinical Models

(2016) F. Li et al.   CANCER RESEARCH

Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity

(2016) Yusuke Ogitani et al.   CANCER SCIENCE

DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1

(2016) Y. Ogitani et al.   CLINICAL CANCER RESEARCH

Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075

(2016) Emily J. Faivre et al.   MOLECULAR CANCER RESEARCH

Processes for Constructing Homogeneous Antibody Drug Conjugates

(2016) David Y. Jackson   ORGANIC PROCESS RESEARCH & DEVELOPMENT

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

Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability

(2016) William A. Kinney et al.   ACS Medicinal Chemistry Letters

Design and Synthesis of Tesirine, a Clinical Antibody–Drug Conjugate Pyrrolobenzodiazepine Dimer Payload

(2016) Arnaud C. Tiberghien et al.   ACS Medicinal Chemistry Letters

ImmunoPET helps predicting the efficacy of antibody-drug conjugates targeting TENB2 and STEAP1

(2016) Simon-Peter Williams et al.   Oncotarget

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

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

(2015) Michael Zengerle et al.   ACS Chemical Biology

Site-Specific Antibody–Drug Conjugates: The Nexus of Bioorthogonal Chemistry, Protein Engineering, and Drug Development

(2015) Paresh Agarwal et al.   BIOCONJUGATE CHEMISTRY

SLC46A3 Is Required to Transport Catabolites of Noncleavable Antibody Maytansine Conjugates from the Lysosome to the Cytoplasm

(2015) K. J. Hamblett et al.   CANCER RESEARCH

Synthetic Approaches to Anti-Inflammatory Macrolactones of the Oxacyclododecindione Type

(2015) Johannes Tauber et al.   EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

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

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

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

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

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

(2015) Lei-lei Fu et al.   Oncotarget

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

(2015) Anastasia Wyce et al.   Oncotarget

Antibody-Drug Conjugates: An Emerging Concept in Cancer Therapy

(2014) Ravi V. J. Chari et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

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

Improving the Therapeutic Index in Cancer Therapy by Using Antibody–Drug Conjugates Designed with a Moderately Cytotoxic Drug

(2014) Serengulam V. Govindan et al.   MOLECULAR PHARMACEUTICS

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

A Potent Anti-CD70 Antibody–Drug Conjugate Combining a Dimeric Pyrrolobenzodiazepine Drug with Site-Specific Conjugation Technology

(2013) Scott C. Jeffrey et al.   BIOCONJUGATE CHEMISTRY

Rapid Measurement of Intracellular Unbound Drug Concentrations

(2013) André Mateus et al.   MOLECULAR PHARMACEUTICS

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE