Advances in targeted degradation of endogenous proteins

First targeted protein degrader hits the clinic

(2019) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)

(2018) Chengwei Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

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

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

Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK)

(2018) Chelsea E. Powell et al.   JOURNAL OF MEDICINAL CHEMISTRY

The dTAG system for immediate and target-specific protein degradation

(2018) Behnam Nabet et al.   Nature Chemical Biology

Facile target validation in an animal model with intracellularly expressed monobodies

(2018) Ankit Gupta et al.   Nature Chemical Biology

A super strong engineered auxin-TIR1 pair

(2018) Ryotaro Yamada et al.   PLANT AND CELL PHYSIOLOGY

Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor

(2018) Sahil Gulati et al.   Nature Communications

Affimer proteins for F-actin: novel affinity reagents that label F-actin in live and fixed cells

(2018) Anna Lopata et al.   Scientific Reports

Dynamics of human protein kinase Aurora A linked to drug selectivity

(2018) Warintra Pitsawong et al.   eLife

Induced protein degradation of anaplastic lymphoma kinase (ALK) by proteolysis targeting chimera (PROTAC)

(2018) Chung Hyo Kang et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Abstract 5236: ARV-110: An androgen receptor PROTAC degrader for prostate cancer

(2018) Taavi Neklesa et al.   CANCER RESEARCH

Role of p53 circuitry in tumorigenesis: A brief review

(2018) Sarfaraj Niazi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Conditional control of fluorescent protein degradation by an auxin-dependent nanobody

(2018) Katrin Daniel et al.   Nature Communications

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

(2018) John Hines et al.   CANCER RESEARCH

Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression

(2018) Yangbing Li et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2018) Quinlan L. Sievers et al.   SCIENCE

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

Identification and Characterization of Von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1

(2017) Andrew P. Crew et al.   JOURNAL OF MEDICINAL CHEMISTRY

Proteasome Structure and Assembly

(2017) Lauren Budenholzer et al.   JOURNAL OF MOLECULAR BIOLOGY

Generation of specific inhibitors of SUMO-1– and SUMO-2/3–mediated protein-protein interactions using Affimer (Adhiron) technology

(2017) David J. Hughes et al.   Science Signaling

Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex

(2017) Teresa A.F. Cardote et al.   STRUCTURE

A Brighter Side to Thalidomide: Its Potential Use in Immunological Disorders

(2017) David Millrine et al.   TRENDS IN MOLECULAR MEDICINE

Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

(2017) Chiara Maniaci et al.   Nature Communications

Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange

(2017) Sandrine Guillard et al.   Nature Communications

Hydrophobic tagging-mediated degradation of Alzheimer's disease related Tau

(2017) Na Gao et al.   RSC Advances

Design and applications of a clamp for Green Fluorescent Protein with picomolar affinity

(2017) Simon Hansen et al.   Scientific Reports

Efforts to Develop KRAS Inhibitors

(2017) Matthew Holderfield   Cold Spring Harbor Perspectives in Medicine

Targeting endogenous proteins for degradation through the affinity-directed protein missile system

(2017) Luke J. Fulcher et al.   Open Biology

Genetic compensation: A phenomenon in search of mechanisms

(2017) Mohamed A. El-Brolosy et al.   PLoS Genetics

Affimer proteins are versatile and renewable affinity reagents

(2017) Christian Tiede et al.   eLife

Generation of specific inhibitors of SUMO-1– and SUMO-2/3–mediated protein-protein interactions using Affimer (Adhiron) technology

(2017) David J. Hughes et al.   Science Signaling

A Novel Destabilizing Domain Based on a Small-Molecule Dependent Fluorophore

(2016) Raul Navarro et al.   ACS Chemical Biology

Ubiquitin chain diversity at a glance

(2016) Masato Akutsu et al.   JOURNAL OF CELL SCIENCE

A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly

(2016) Florian I. Schmidt et al.   JOURNAL OF EXPERIMENTAL MEDICINE

The Keap1-Nrf2-ARE Pathway As a Potential Preventive and Therapeutic Target: An Update

(2016) Meng-Chen Lu et al.   MEDICINAL RESEARCH REVIEWS

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

The increasing complexity of the ubiquitin code

(2016) Richard Yau et al.   NATURE CELL BIOLOGY

Inhibition of RAS function through targeting an allosteric regulatory site

(2016) Russell Spencer-Smith et al.   Nature Chemical Biology

In vivo aspects of protein folding and quality control

(2016) D. Balchin et al.   SCIENCE

Peptides in headlock – a novel high-affinity and versatile peptide-binding nanobody for proteomics and microscopy

(2016) Michael B. Braun et al.   Scientific Reports

Rapid Protein Depletion in Human Cells by Auxin-Inducible Degron Tagging with Short Homology Donors

(2016) Toyoaki Natsume et al.   Cell Reports

An affinity-directed protein missile system for targeted proteolysis

(2016) Luke J. Fulcher et al.   Open Biology

Destabilizing an interacting motif strengthens the association of a designed ankyrin repeat protein with tubulin

(2016) Shoeb Ahmad et al.   Scientific Reports

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

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

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

(2015) Michael Zengerle et al.   ACS Chemical Biology

Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL

(2015) Ashton C. Lai et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Small-Molecule-Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging

(2015) Jeffrey L. Gustafson et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Inhibitor of apoptosis proteins as intracellular signaling intermediates

(2015) Andrew J. Kocab et al.   FEBS Journal

Selection of human single domain antibodies recognizing the CMYC protein using enhanced intracellular antibody capture

(2015) J. Zeng et al.   JOURNAL OF IMMUNOLOGICAL METHODS

Monitoring Interactions and Dynamics of Endogenous Beta-catenin With Intracellular Nanobodies in Living Cells

(2015) Bjoern Traenkle et al.   MOLECULAR & CELLULAR PROTEOMICS

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

(2015) Jan Krönke et al.   NATURE

Tunable and reversible drug control of protein production via a self-excising degron

(2015) Hokyung K Chung et al.   Nature Chemical Biology

Catalytic in vivo protein knockdown by small-molecule PROTACs

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

Protein neddylation: beyond cullin–RING ligases

(2015) Radoslav I. Enchev et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Alleviation of off-target effects from vector-encoded shRNAs via codelivered RNA decoys

(2015) Stefan Mockenhaupt et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells

(2015) Marie-Magdelaine Coudé et al.   Oncotarget

Repurposing an endogenous degradation system for rapid and targeted depletion of C. elegans proteins

(2014) S. T. Armenti et al.   DEVELOPMENT

Stratifying fascin and cortactin function in invadopodium formation using inhibitory nanobodies and targeted subcellular delocalization

(2014) Isabel Van Audenhove et al.   FASEB JOURNAL

Functional inhibition of β-catenin-mediatedWnt signaling by intracellular VHHantibodies

(2014) Laura E Newnham et al.   mAbs

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

(2014) Eric S. Fischer et al.   NATURE

Pharmacological targeting of the pseudokinase Her3

(2014) Ting Xie et al.   Nature Chemical Biology

A robust pipeline for rapid production of versatile nanobody repertoires

(2014) Peter C Fridy et al.   NATURE METHODS

Drugging the undruggable RAS: Mission Possible?

(2014) Adrienne D. Cox et al.   NATURE REVIEWS DRUG DISCOVERY

Adhiron: a stable and versatile peptide display scaffold for molecular recognition applications

(2014) Christian Tiede et al.   PROTEIN ENGINEERING DESIGN & SELECTION

Cancer cell death induced by novel small molecules degrading the TACC3 protein via the ubiquitin–proteasome pathway

(2014) N Ohoka et al.   Cell Death & Disease

Replacing Antibodies: Engineering New Binding Proteins

(2013) Scott Banta et al.   Annual Review of Biomedical Engineering

In vivocharacterization of the properties of SUMO1-specific monobodies

(2013) Anja Berndt et al.   BIOCHEMICAL JOURNAL

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

(2013) Jakob Lovén et al.   CELL

A Bilirubin-Inducible Fluorescent Protein from Eel Muscle

(2013) Akiko Kumagai et al.   CELL

Cullin-RING Ligases as Attractive Anti-cancer Targets

(2013) Yongchao Zhao et al.   CURRENT PHARMACEUTICAL DESIGN

L-Plastin Nanobodies Perturb Matrix Degradation, Podosome Formation, Stability and Lifetime in THP-1 Macrophages

(2013) Sarah De Clercq et al.   PLoS One

Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains

(2013) F. Sha et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Design, construction, and characterization of a second-generation DARPin library with reduced hydrophobicity

(2013) Markus A. Seeger et al.   PROTEIN SCIENCE

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

(2013) J. Kronke et al.   SCIENCE

PAPTi: A Peptide Aptamer Interference Toolkit for Perturbation of Protein-Protein Interaction Networks

(2013) Johannes T. -H. Yeh et al.   Scientific Reports

Epitope-Guided Engineering of Monobody Binders for in Vivo Inhibition of Erk-2 Signaling

(2012) Jasdeep K. Mann et al.   ACS Chemical Biology

Small-Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1α

(2012) Dennis L. Buckley et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The Ubiquitin Code

(2012) David Komander et al.   Annual Review of Biochemistry

Double protein knockdown of cIAP1 and CRABP-II using a hybrid molecule consisting of ATRA and IAPs antagonist

(2012) Yukihiro Itoh et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Nanobody-induced perturbation of LFA-1/L-plastin phosphorylation impairs MTOC docking, immune synapse formation and T cell activation

(2012) Sarah De Clercq et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

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

Kinetics of PKCε Activating and Inhibiting Llama Single Chain Antibodies and Their Effect on PKCε Translocation in HeLa Cells

(2012) Milla Summanen et al.   PLoS One

A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity

(2012) M. Jinek et al.   SCIENCE

Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein

(2011) Keiichiro Okuhira et al.   FEBS LETTERS

Identification of Diaryl Ether-Based Ligands for Estrogen-Related Receptor α as Potential Antidiabetic Agents

(2011) Raymond J. Patch et al.   JOURNAL OF MEDICINAL CHEMISTRY

Teaching an Old Scaffold New Tricks: Monobodies Constructed Using Alternative Surfaces of the FN3 Scaffold

(2011) Akiko Koide et al.   JOURNAL OF MOLECULAR BIOLOGY

Small-molecule hydrophobic tagging–induced degradation of HaloTag fusion proteins

(2011) Taavi K Neklesa et al.   Nature Chemical Biology

Fluorescent fusion protein knockout mediated by anti-GFP nanobody

(2011) Emmanuel Caussinus et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Isoform-specific monobody inhibitors of small ubiquitin-related modifiers engineered using structure-guided library design

(2011) R. N. Gilbreth et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A llama-derived gelsolin single-domain antibody blocks gelsolin–G-actin interaction

(2010) Anske Van den Abbeele et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Affibody molecules: Engineered proteins for therapeutic, diagnostic and biotechnological applications

(2010) J. Löfblom et al.   FEBS LETTERS

Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes

(2010) K. Tachibana-Konwalski et al.   GENES & DEVELOPMENT

Single Domain Intracellular Antibodies from Diverse Libraries

(2010) Tomoyuki Tanaka et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Protein Knockdown Using Methyl Bestatin−Ligand Hybrid Molecules: Design and Synthesis of Inducers of Ubiquitination-Mediated Degradation of Cellular Retinoic Acid-Binding Proteins

(2010) Yukihiro Itoh et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain

(2010) John Wojcik et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)

(2010) D. L. Mallery et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

N-terminal engineering of amyloid-β-binding Affibody molecules yields improved chemical synthesis and higher binding affinity

(2010) Joel Lindgren et al.   PROTEIN SCIENCE

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

CRISPR/Cas, the Immune System of Bacteria and Archaea

(2010) P. Horvath et al.   SCIENCE

An alpaca single-domain antibody blocks filopodia formation by obstructing L-plastin-mediated F-actin bundling

(2009) Veerle Delanote et al.   FASEB JOURNAL

An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer

(2009) Teresa A. Soucy et al.   NATURE

An auxin-based degron system for the rapid depletion of proteins in nonplant cells

(2009) Kohei Nishimura et al.   NATURE METHODS

Isolation and Functional Characterization of Single Domain Antibody Modulators of Caspase-3 and Apoptosis

(2008) Katrina McGonigal et al.   APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY

Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics

(2008) Ashley R. Schneekloth et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Selection and characterization of Affibody® ligands to the transcription factor c-Jun

(2008) Emma Lundberg et al.   BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY

Small Molecules Destabilize cIAP1 by Activating Auto-ubiquitylation

(2008) Keiko Sekine et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A drug-controllable tag for visualizing newly synthesized proteins in cells and whole animals

(2008) M. Z. Lin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cullin-RING ubiquitin ligases: global regulation and activation cycles

(2008) Dimple R Bosu et al.   Cell Division

An scFv Intrabody against the Nonamyloid Component of α-Synuclein Reduces Intracellular Aggregation and Toxicity

(2007) Sandra M. Lynch et al.   JOURNAL OF MOLECULAR BIOLOGY