The rise and rise of protein degradation: Opportunities and challenges ahead

Targeted protein degraders crowd into the clinic

(2021) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

The PROTACtable genome

(2021) Melanie Schneider et al.   NATURE REVIEWS DRUG DISCOVERY

Proteolysis‐targeting chimeras in drug development: A safety perspective

(2020) Kevin Moreau et al.   BRITISH JOURNAL OF PHARMACOLOGY

Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity

(2020) Xuan Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Multiple Cereblon genetic changes associate with acquired resistance to Lenalidomide or Pomalidomide in Multiple Myeloma

(2020) Sarah Gooding et al.   BLOOD

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

(2020) Andy Pike et al.   DRUG DISCOVERY TODAY

DT2216—a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas

(2020) Yonghan He et al.   Journal of Hematology & Oncology

Lysosome-targeting chimaeras for degradation of extracellular proteins

(2020) Steven M. Banik et al.   NATURE

Rational discovery of molecular glue degraders via scalable chemical profiling

(2020) Cristina Mayor-Ruiz et al.   Nature Chemical Biology

Selective Degradation of GSPT1 by Cereblon Modulators Identified via a Focused Combinatorial Library

(2020) Chelsea E. Powell et al.   ACS Chemical Biology

First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo

(2020) Mingming Wei et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications

(2020) Laura Goracci et al.   JOURNAL OF MEDICINAL CHEMISTRY

Bardoxolone conjugation enables targeted protein degradation of BRD4

(2020) Bingqi Tong et al.   Scientific Reports

Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation

(2020) Lu Lv et al.   eLife

Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development

(2020) Katherine A. Donovan et al.   CELL

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

(2019) Xiuyun Sun et al.   Cell Discovery

Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications

(2019) Carl C. Ward et al.   ACS Chemical Biology

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

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

Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-mediated Targeted Protein Degradation

(2019) George M Burslem et al.   CANCER RESEARCH

Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation

(2019) Kinam Park et al.   JOURNAL OF CONTROLLED RELEASE

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

Plasticity of the Cullin-RING Ligase Repertoire Shapes Sensitivity to Ligand-Induced Protein Degradation

(2019) Cristina Mayor-Ruiz et al.   MOLECULAR CELL

Cellular Resistance Mechanisms to Targeted Protein Degradation Converge Toward Impairment of the Engaged Ubiquitin Transfer Pathway

(2019) Philipp Ottis et al.   ACS Chemical Biology

Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15

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

Targeted protein degradation: expanding the toolbox

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

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

(2019) Xinlin Du et al.   STRUCTURE

AUTACs: Cargo-Specific Degraders Using Selective Autophagy

(2019) Daiki Takahashi et al.   MOLECULAR CELL

Targeting the C481S Ibrutinib-Resistance Mutation in Bruton’s Tyrosine Kinase Using PROTAC-Mediated Degradation

(2018) Alexandru D. Buhimschi et al.   BIOCHEMISTRY

PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies

(2018) Yonghui Sun et al.   CELL RESEARCH

Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation

(2018) Nobumichi Ohoka et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Protein targeting chimeric molecules specific for bromodomain and extra-terminal motif family proteins are active against pre-clinical models of multiple myeloma

(2018) Xiaohui Zhang et al.   LEUKEMIA

Delineating the role of cooperativity in the design of potent PROTACs for BTK

(2018) Adelajda Zorba et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Systematic analysis of protein turnover in primary cells

(2018) Toby Mathieson et al.   Nature Communications

Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome

(2018) Katherine A Donovan et al.   eLife

Bruton's Tyrosine Kinase degradation as a therapeutic strategy for cancer

(2018) Dennis Dobrovolsky et al.   BLOOD

Beyond the Rule of 5: Lessons Learned from AbbVie’s Drugs and Compound Collection

(2017) David A. DeGoey 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

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

(2017) Ting Han et al.   SCIENCE

Central Nervous System Multiparameter Optimization Desirability: Application in Drug Discovery

(2016) Travis T. Wager et al.   ACS Chemical Neuroscience

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

(2015) Michael Zengerle et al.   ACS Chemical Biology

Catalytic in vivo protein knockdown by small-molecule PROTACs

(2015) Daniel P Bondeson et al.   Nature Chemical Biology

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

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

(2014) Eric S. Fischer et al.   NATURE

The secret life of kinases: functions beyond catalysis

(2011) Jens Rauch et al.   Cell Communication and Signaling

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE