E3 Ligase Ligands in Successful PROTACs: An Overview of Syntheses and Linker Attachment Points

CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia

(2021) Joshua D. Hansen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Hi-JAK-ing the ubiquitin system: The design and physicochemical optimisation of JAK PROTACs

(2020) Rishi R. Shah et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

(2020) George M. Burslem et al.   CELL

Catalytic enantioselective formal synthesis of MDM2 antagonist RG7388 and its analogues

(2020) Xue‐Jie Zou et al.   CHINESE JOURNAL OF CHEMISTRY

Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma

(2020) Joshua D. Hansen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Optical Control of Small Molecule-Induced Protein Degradation

(2020) Yuta Naro et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

PHOTACs enable optical control of protein degradation

(2020) Martin Reynders et al.   Science Advances

Design and synthesis of new lenalidomide analogs via Suzuki cross‐coupling reaction

(2020) Donghuai Xiao et al.   ARCHIV DER PHARMAZIE

Selective CDK6 degradation mediated by cereblon, VHL, and novel IAP-recruiting PROTACs

(2020) Niall A. Anderson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design and synthesis of selective degraders of EGFRL858R/T790M mutant

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

Azo-PROTAC: Novel Light-Controlled Small-Molecule Tool for Protein Knockdown

(2020) Yu-Hui Jin et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2020) Michael Gütschow et al.   SYNTHESIS-STUTTGART

A Nimbolide-Based Kinase Degrader Preferentially Degrades Oncogenic BCR-ABL

(2020) Bingqi Tong et al.   ACS Chemical Biology

A Buchwald‐Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3‐Ligase PROTACs

(2020) Thomas G Hayhow et al.   CHEMISTRY-A EUROPEAN JOURNAL

Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines

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

A Cellular Mechanism to Detect and Alleviate Reductive Stress

(2020) Andrew G. Manford et al.   CELL

PROTAC-DB: an online database of PROTACs

(2020) Gaoqi Weng et al.   NUCLEIC ACIDS RESEARCH

Bardoxolone conjugation enables targeted protein degradation of BRD4

(2020) Bingqi Tong et al.   Scientific Reports

Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER)

(2019) Jiantao Hu 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

Developing potent PROTACs tools for selective degradation of HDAC6 protein

(2019) Zixuan An et al.   Protein & Cell

Degradation of Bruton’s tyrosine kinase mutants by PROTACs for potential treatment of ibrutinib-resistant non-Hodgkin lymphomas

(2019) Yonghui Sun et al.   LEUKEMIA

Selective Degradation of CDK6 by a Palbociclib Based PROTAC

(2019) Sandeep Rana et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

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

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

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1 (MCL1)

(2019) James William Papatzimas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction

(2019) Xing Qiu et al.   ORGANIC LETTERS

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

(2019) M Catarina Silva et al.   eLife

Pomalidomide hybrids act as proteolysis targeting chimeras: Synthesis, anticancer activity and B-Raf degradation

(2019) Hong Chen et al.   BIOORGANIC CHEMISTRY

Development of Multifunctional Histone Deacetylase 6 Degraders with Potent Antimyeloma Activity

(2019) Hao Wu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Harnessing the anti-cancer natural product nimbolide for targeted protein degradation

(2019) Jessica N. Spradlin et al.   Nature Chemical Biology

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

(2019) William Farnaby et al.   Nature Chemical Biology

Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16

(2019) Xiaoyu Zhang et al.   Nature Chemical Biology

Targeting IRAK4 for Degradation with PROTACs

(2019) Joao Nunes et al.   ACS Medicinal Chemistry Letters

Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations

(2019) Mélissanne de Wispelaere et al.   Nature Communications

Development of selective small molecule MDM2 degraders based on nutlin

(2019) Bo Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders

(2019) Shang Su et al.   JOURNAL OF MEDICINAL CHEMISTRY

Simple Structural Modifications Converting a Bona Fide MDM2 PROTAC Degrader into a Molecular Glue Molecule: A Cautionary Tale in the Design of PROTAC Degraders

(2019) Jiuling Yang et al.   JOURNAL OF MEDICINAL CHEMISTRY

TrkC-Targeted Kinase Inhibitors And PROTACs

(2019) Bosheng Zhao et al.   MOLECULAR PHARMACEUTICS

Reversible Spatiotemporal Control of Induced Protein Degradation by Bistable PhotoPROTACs

(2019) Patrick Pfaff et al.   ACS Central Science

Development of Small Molecule Chimeras That Recruit AhR E3 Ligase to Target Proteins

(2019) Nobumichi Ohoka et al.   ACS Chemical Biology

Triazol: a privileged scaffold for proteolysis targeting chimeras

(2019) Li-Wen Xia et al.   Future Medicinal Chemistry

Light-Induced Protein Degradation with Photocaged PROTACs

(2019) Gang Xue et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeted protein degradation: expanding the toolbox

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

Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide

(2019) Fangqing Zhang et al.   BIOORGANIC & MEDICINAL CHEMISTRY

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

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

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

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

Targeted Protein Degradation by Chimeric Small Molecules, PROTACs and SNIPERs

(2019) Mikihiko Naito et al.   Frontiers in Chemistry

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

(2018) Mette Ishoey et al.   ACS Chemical Biology

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

Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure-Degradation Relationships

(2018) George M. Burslem et al.   ChemMedChem

Targeted protein degradation and the enzymology of degraders

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

Phthalimide conjugations for the degradation of oncogenic PI3K

(2018) Wenlu Li 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

Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766)

(2018) Nicola E. A. Chessum et al.   JOURNAL OF MEDICINAL CHEMISTRY

A practical diastereoselective synthesis of (−)-bestatin

(2018) Suisheng Shang et al.   JOURNAL OF PEPTIDE SCIENCE

Modulating PCAF/GCN5 Immune Cell Function through a PROTAC Approach

(2018) Zuni I. Bassi et al.   ACS Chemical Biology

Homo-PROTACs for the Chemical Knockdown of Cereblon

(2018) Christian Steinebach et al.   ACS Chemical Biology

Chemically induced degradation of CK2 by proteolysis targeting chimeras based on a ubiquitin–proteasome pathway

(2018) Hong Chen et al.   BIOORGANIC CHEMISTRY

Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs

(2018) Sainan An et al.   EBioMedicine

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

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

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

Development of Protein Degradation Inducers of Androgen Receptor by Conjugation of Androgen Receptor Ligands and Inhibitor of Apoptosis Protein Ligands

(2017) Norihito Shibata 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

A Molecular Mechanism To Switch the Aryl Hydrocarbon Receptor from a Transcription Factor to an E3 Ubiquitin Ligase

(2017) Sandra Luecke-Johansson et al.   MOLECULAR AND CELLULAR BIOLOGY

Structural basis of PROTAC cooperative recognition for selective protein degradation

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

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

(2017) Ting Han et al.   SCIENCE

Targeting the Allosteric Site of Oncoprotein BCR-ABL as an Alternative Strategy for Effective Target Protein Degradation

(2017) Kenichiro Shimokawa et al.   ACS Medicinal Chemistry Letters

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

(2017) Chiara Maniaci et al.   Nature Communications

SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

(2017) Antoine Daina et al.   Scientific Reports

Small-Molecule PROTACS: New Approaches to Protein Degradation

(2016) Momar Toure et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

New strategy for renal fibrosis: Targeting Smad3 proteins for ubiquitination and degradation

(2016) Xin Wang et al.   BIOCHEMICAL PHARMACOLOGY

Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development

(2016) Jasmin Lohbeck et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery and Development of Kelch-like ECH-Associated Protein 1. Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction Inhibitors: Achievements, Challenges, and Future Directions

(2016) Zheng-Yu Jiang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery

(2016) Thomas G. Davies et al.   JOURNAL OF MEDICINAL CHEMISTRY

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

Structural insights into the catalysis and regulation of E3 ubiquitin ligases

(2016) Lori Buetow et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Practical Synthesis of MDM2 Antagonist RG7388. Part 2: Development of the Cu(I) Catalyzed [3 + 2] Asymmetric Cycloaddition Process for the Manufacture of Idasanutlin

(2016) Gösta Rimmler et al.   ORGANIC PROCESS RESEARCH & DEVELOPMENT

Practical Synthesis of MDM2 Antagonist RG7388. Part 1: A Cu(II)-Catalyzed Asymmetric [3 + 2] Cycloaddition

(2016) Lianhe Shu et al.   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

New synthesis route for the preparation of pomalidomide

(2016) Daowei Huang et al.   SYNTHETIC COMMUNICATIONS

Protein Degradation by In-Cell Self-Assembly of Proteolysis Targeting Chimeras

(2016) Honorine Lebraud et al.   ACS Central Science

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

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Scalable and green process for the synthesis of anticancer drug lenalidomide

(2015) Yuri Ponomaryov et al.   Chemistry of Heterocyclic Compounds

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

(2015) Jan Krönke et al.   NATURE

Catalytic in vivo protein knockdown by small-molecule PROTACs

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

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

Design of Chemically Stable, Potent, and Efficacious MDM2 Inhibitors That Exploit the Retro-Mannich Ring-Opening-Cyclization Reaction Mechanism in Spiro-oxindoles

(2014) Angelo Aguilar et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

Perilous journey: a tour of the ubiquitin–proteasome system

(2014) Gary Kleiger et al.   TRENDS IN CELL BIOLOGY

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

Protein quality control and elimination of protein waste: The role of the ubiquitin–proteasome system

(2013) Ingo Amm et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Development of hybrid small molecules that induce degradation of estrogen receptor-alpha and necrotic cell death in breast cancer cells

(2013) Keiichiro Okuhira et al.   CANCER SCIENCE

ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1

(2013) J Han et al.   CELL DEATH AND DIFFERENTIATION

Optimization of Benzodiazepinones as Selective Inhibitors of the X-Linked Inhibitor of Apoptosis Protein (XIAP) Second Baculovirus IAP Repeat (BIR2) Domain

(2013) Robert F. Kester et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development

(2013) Qingjie Ding et al.   JOURNAL OF MEDICINAL CHEMISTRY

Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders

(2013) Philip B Busbee et al.   NUTRITION REVIEWS

Efficient and Scalable Synthesis of Bardoxolone Methyl (CDDO-methyl Ester)

(2013) Liangfeng Fu et al.   ORGANIC LETTERS

Alternative synthesis of lenalidomide

(2013) A. N. Balaev et al.   PHARMACEUTICAL CHEMISTRY JOURNAL

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

(2013) J. Kronke et al.   SCIENCE

Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development

(2013) Binh Vu et al.   ACS Medicinal Chemistry Letters

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

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

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

Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration

(2012) Matthew Hoffmann et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Dissecting Fragment-Based Lead Discovery at the von Hippel-Lindau Protein:Hypoxia Inducible Factor 1α Protein-Protein Interface

(2012) Inge Van Molle et al.   CHEMISTRY & BIOLOGY

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

Targeting IAP proteins for therapeutic intervention in cancer

(2012) Simone Fulda et al.   NATURE REVIEWS DRUG DISCOVERY

Design, synthesis and biological evaluation of nuclear receptor-degradation inducers

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

Design and synthesis of estrogen receptor degradation inducer based on a protein knockdown strategy

(2011) Yosuke Demizu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide

(2011) Y. X. Zhu et al.   BLOOD

Teratogenic effects of thalidomide: molecular mechanisms

(2011) Takumi Ito et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

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

Functional analysis of the RNF114 psoriasis susceptibility gene implicates innate immune responses to double-stranded RNA in disease pathogenesis

(2011) Marie-José Bijlmakers et al.   HUMAN MOLECULAR GENETICS

Novel thalidomide analogues with potent NFκB and TNF expression inhibition

(2011) Sing Yee Yeung et al.   MedChemComm

Design, synthesis and biological evaluation of new thalidomide analogues as TNF-α and IL-6 production inhibitors

(2010) Charlotte Chaulet et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Will the Ubiquitin System Furnish as Many Drug Targets as Protein Kinases?

(2010) Philip Cohen et al.   CELL

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

New thalidomide analogues derived through Sonogashira or Suzuki reactions and their TNF expression inhibition profiles

(2009) Scott G. Stewart et al.   BIOORGANIC & MEDICINAL CHEMISTRY

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

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