Development of targeted protein degradation therapeutics

Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase

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

First targeted protein degrader hits the clinic

(2019) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

Development of Dual and Selective Degraders of Cyclin-Dependent Kinases 4 and 6

(2019) Baishan Jiang et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

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

(2019) M Catarina Silva et al.   eLife

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

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

Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders

(2018) Mette Ishoey et al.   ACS Chemical Biology

Targeted protein degradation and the enzymology of degraders

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

Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase–mTORC1 Translational Pathway

(2018) Charlotte C. Bavley et al.   JOURNAL OF NEUROSCIENCE

Linkers for protein degradation

(2018) Philip P. Chamberlain   Nature Chemical Biology

Plasticity in binding confers selectivity in ligand-induced protein degradation

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

Unexplored therapeutic opportunities in the human genome

(2018) Tudor I. Oprea et al.   NATURE REVIEWS DRUG DISCOVERY

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

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

(2018) Quinlan L. Sievers et al.   BLOOD

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

SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate

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

UBE2G1 governs the destruction of cereblon neomorphic substrates

(2018) Gang Lu et al.   eLife

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

(2018) Katherine A Donovan et al.   eLife

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

(2018) John Hines et al.   CANCER RESEARCH

Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel–Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7

(2018) Vittoria Zoppi 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

A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos

(2017) Mary E. Matyskiela et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates

(2017) Thang Van Nguyen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

(2017) Ting Han et al.   SCIENCE

pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate of the CRL4CRBN ubiquitin ligase

(2017) Jian An et al.   Nature Communications

Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon

(2016) Thang Van Nguyen et al.   MOLECULAR CELL

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

Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL

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

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

Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains

(2015) Junwei Shi et al.   NATURE BIOTECHNOLOGY

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

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

Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN

(2013) Anita K. Gandhi et al.   BRITISH JOURNAL OF HAEMATOLOGY

A Comprehensive Mathematical Model for Three-Body Binding Equilibria

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

Mechanisms and function of substrate recruitment by F-box proteins

(2013) Jeffrey R. Skaar et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

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

Small-Molecule Stabilization of Protein-Protein Interactions: An Underestimated Concept in Drug Discovery?

(2012) Philipp Thiel et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Development of target protein-selective degradation inducer for protein knockdown

(2011) Yukihiro Itoh et al.   BIOORGANIC & MEDICINAL CHEMISTRY

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

Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease

(2011) James H. Kim et al.   TOXICOLOGICAL SCIENCES

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

Jasmonate perception by inositol-phosphate-potentiated COI1–JAZ co-receptor

(2010) Laura B. Sheard et al.   NATURE

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

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

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

Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer

(2008) A Rodriguez-Gonzalez et al.   ONCOGENE