Unifying Catalysis Framework to Dissect Proteasomal Degradation Paradigms

The Rise of Molecular Glues

(2021) Stuart L. Schreiber   CELL

Reversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide

(2021) Max Jan et al.   Science Translational Medicine

Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins

(2021) Ryosuke Shirasaki et al.   Cell Reports

High-Throughput Quantitative Assay Technologies for Accelerating the Discovery and Optimization of Targeted Protein Degradation Therapeutics

(2021) Jeffrey R. Simard et al.   SLAS Discovery

Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta

(2021) Nan Bai et al.   Journal of Chemical Information and Modeling

TRIP12 promotes small-molecule-induced degradation through K29/K48-branched ubiquitin chains

(2021) Ai Kaiho-Soma et al.   MOLECULAR CELL

Target protein deglycosylation in living cells by a nanobody-fused split O-GlcNAcase

(2021) Yun Ge et al.   Nature Chemical Biology

Targeting oncoproteins with a positive selection assay for protein degraders

(2021) Vidyasagar Koduri et al.   Science Advances

Targeted protein degraders crowd into the clinic

(2021) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

The rise of covalent proteolysis targeting chimeras

(2021) Ronen Gabizon et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Engineering a Proximity-Directed O-GlcNAc Transferase for Selective Protein O-GlcNAcylation in Cells

(2020) Daniel H. Ramirez et al.   ACS Chemical Biology

Proteolysis‐targeting chimeras in drug development: A safety perspective

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

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

(2020) George M. Burslem et al.   CELL

PIKES Analysis Reveals Response to Degraders and Key Regulatory Mechanisms of the CRL4 Network

(2020) Kurt M. Reichermeier et al.   MOLECULAR CELL

Harnessing the Power of Proteolysis for Targeted Protein Inactivation

(2020) Rati Verma et al.   MOLECULAR CELL

bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA)

(2020) Shuhui Lim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Fundamental aspects of DMPK optimization of targeted protein degraders

(2020) Carina Cantrill et al.   DRUG DISCOVERY TODAY

Monomeric targeted protein degraders

(2020) Emily J. Hanan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders

(2020) Benjamin R. Bellenie et al.   JOURNAL OF MEDICINAL CHEMISTRY

Multispecific drugs herald a new era of biopharmaceutical innovation

(2020) Raymond J. Deshaies   NATURE

Unifying principles of bifunctional, proximity-inducing small molecules

(2020) Christopher J. Gerry et al.   Nature Chemical Biology

Critical Assessment of Targeted Protein Degradation as a Research Tool and Pharmacological Modality

(2020) Milka Kostic et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Enzyme dynamics: Looking beyond a single structure

(2020) Pratul Agarwal et al.   ChemCatChem

Targeted protein degradation: current and future challenges

(2020) Alexander Hanzl et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Phosphorylation-Inducing Chimeric Small Molecules

(2020) Sachini U. Siriwardena et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Lysosome-targeting chimaeras for degradation of extracellular proteins

(2020) Steven M. Banik et al.   NATURE

The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K

(2020) Mikołaj Słabicki et al.   NATURE

Rational discovery of molecular glue degraders via scalable chemical profiling

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

Targeted protein degradation as a powerful research tool in basic biology and drug target discovery

(2020) Tao Wu et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface

(2020) Uddhav K. Shigdel et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Native Mass Spectrometry Can Effectively Predict PROTAC Efficacy

(2020) Rebecca Beveridge et al.   ACS Central Science

A suite of mathematical solutions to describe ternary complex formation and their application to targeted protein degradation by hetero-bifunctional ligands

(2020) Bomie Han   JOURNAL OF BIOLOGICAL CHEMISTRY

Improved Accuracy for Modeling PROTAC-Mediated Ternary Complex Formation and Targeted Protein Degradation via New In Silico Methodologies

(2020) Michael L. Drummond et al.   Journal of Chemical Information and Modeling

A kinetic proofreading model for bispecific protein degraders

(2020) Derek W. Bartlett et al.   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

Unexpected specificity within dynamic transcriptional protein–protein complexes

(2020) Matthew J. Henley et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer

(2020) Francesca Petralia et al.   CELL

Small-molecule-induced polymerization triggers degradation of BCL6

(2020) Mikołaj Słabicki et al.   NATURE

Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes

(2020) James Schiemer et al.   Nature Chemical Biology

Systems biology in cardiovascular disease: a multiomics approach

(2020) Abhishek Joshi et al.   Nature Reviews Cardiology

High-Throughput Affinity Measurements of Transcription Factor and DNA Mutations Reveal Affinity and Specificity Determinants

(2020) Arjun K. Aditham et al.   Cell Systems

Exquisitely Specific anti-KRAS Biodegraders Inform on the Cellular Prevalence of Nucleotide-Loaded States

(2020) Shuhui Lim et al.   ACS Central Science

CDK Family PROTAC Profiling Reveals Distinct Kinetic Responses and Cell Cycle–Dependent Degradation of CDK2

(2020) Kristin M. Riching et al.   SLAS Discovery

Target Validation Using PROTACs: Applying the Four Pillars Framework

(2020) Radosław P. Nowak et al.   SLAS Discovery

Small-Molecule Approaches to Targeted Protein Degradation

(2020) Tyler B. Faust et al.   Annual Review of Cancer Biology-Series

Building ubiquitination machineries: E3 ligase multi-subunit assembly and substrate targeting by PROTACs and molecular glues

(2020) Sarath Ramachandran et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction

(2019) Kyle R. Simonetta et al.   Nature Communications

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

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

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

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

Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models

(2019) M Catarina Silva et al.   eLife

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

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

(2019) Philipp Ottis et al.   ACS Chemical Biology

Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds

(2019) Zhaoyang Li et al.   NATURE

Targeted protein degradation: expanding the toolbox

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

Evolution of Cereblon-Mediated Protein Degradation as a Therapeutic Modality

(2019) Philip P. Chamberlain et al.   ACS Medicinal Chemistry Letters

Evolution and regulation of nitrogen flux through compartmentalized metabolic networks in a marine diatom

(2019) Sarah R. Smith et al.   Nature Communications

Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study

(2019) Sayumi Yamazoe et al.   JOURNAL OF MEDICINAL CHEMISTRY

AUTACs: Cargo-Specific Degraders Using Selective Autophagy

(2019) Daiki Takahashi et al.   MOLECULAR CELL

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

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

The size matters? A computational tool to design bivalent ligands

(2018) Laura Pérez-Benito et al.   BIOINFORMATICS

Targeted protein degradation and the enzymology of degraders

(2018) Stewart L Fisher et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

The dTAG system for immediate and target-specific protein degradation

(2018) Behnam Nabet et al.   Nature Chemical Biology

Plasticity in binding confers selectivity in ligand-induced protein degradation

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

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

Chemically induced proximity in biology and medicine

(2018) Benjamin Z. Stanton et al.   SCIENCE

Systematic analysis of protein turnover in primary cells

(2018) Toby Mathieson et al.   Nature Communications

Quantitative Live-Cell Kinetic Degradation and Mechanistic Profiling of PROTAC Mode of Action

(2018) Kristin M. Riching et al.   ACS Chemical Biology

Genome-wide screen identifies cullin-RING ligase machinery required for lenalidomide-dependent CRL4CRBN activity

(2018) Quinlan L. Sievers et al.   BLOOD

SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate

(2018) Mary E. Matyskiela et al.   Nature Chemical Biology

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

(2018) Katherine A Donovan et al.   eLife

Development of a Novel B-Cell Lymphoma 6 (BCL6) PROTAC To Provide Insight into Small Molecule Targeting of BCL6

(2018) William McCoull et al.   ACS Chemical Biology

A Biophysical Perspective on Enzyme Catalysis

(2018) Pratul K. Agarwal   BIOCHEMISTRY

Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN

(2018) Quinlan L. Sievers et al.   SCIENCE

Molecular recognition of ternary complexes: a new dimension in the structure-guided design of chemical degraders

(2017) Scott J. Hughes et al.   Essays in Biochemistry

Selective degradation of splicing factor CAPERα by anticancer sulfonamides

(2017) Taisuke Uehara et al.   Nature Chemical Biology

Structural basis of PROTAC cooperative recognition for selective protein degradation

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

Ubiquitylation at the crossroads of development and disease

(2017) Michael Rape   NATURE REVIEWS MOLECULAR CELL BIOLOGY

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

(2017) Ting Han et al.   SCIENCE

Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6

(2017) Nina Kerres et al.   Cell Reports

Types of Ubiquitin Ligases

(2016) Francesca Ester Morreale et al.   CELL

HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins

(2015) Dennis L. Buckley et al.   ACS Chemical Biology

Catalytic in vivo protein knockdown by small-molecule PROTACs

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

The demographics of the ubiquitin system

(2015) Michael J. Clague et al.   TRENDS IN CELL BIOLOGY

Current Compound Coverage of the Kinome

(2014) Ye Hu et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Comprehensive Mathematical Model for Three-Body Binding Equilibria

(2013) Eugene F. Douglass et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells

(2013) J. Kronke et al.   SCIENCE

The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins

(2013) G. Lu et al.   SCIENCE

Flexibility, Diversity, and Cooperativity: Pillars of Enzyme Catalysis

(2011) Gordon G. Hammes et al.   BIOCHEMISTRY

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

Free-Energy Landscape of Enzyme Catalysis†

(2008) Stephen J. Benkovic et al.   BIOCHEMISTRY

Cooperativity and biological complexity

(2008) Adrian Whitty   Nature Chemical Biology