The PROTAC technology in drug development

Selective degradation of BET proteins with dBET1, a proteolysis-targeting chimera, potently reduces pro-inflammatory responses in lipopolysaccharide-activated microglia

(2018) Kelly M. DeMars et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

PROTACs: An Emerging Targeting Technique for Protein Degradation in Drug Discovery

(2018) Shanshan Gu et al.   BIOESSAYS

Development of the first small molecule histone deacetylase 6 (HDAC6) degraders

(2018) Ka Yang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Hypoxia-selective allosteric destabilization of activin receptor-like kinases: A potential therapeutic avenue for prophylaxis of heterotopic ossification

(2018) Guorong Lu et al.   BONE

Multiplexed Proteome Dynamics Profiling Reveals Mechanisms Controlling Protein Homeostasis

(2018) Mikhail M. Savitski et al.   CELL

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

Chemical Protein Degradation Approach and its Application to Epigenetic Targets

(2018) Yukihiro Itoh   CHEMICAL RECORD

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

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

Phthalimide conjugations for the degradation of oncogenic PI3K

(2018) Wenlu Li 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

Ubiquitination: Friend and foe in cancer

(2018) Mohammed A. Mansour   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK)

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

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

(2018) Chong Qin et al.   JOURNAL OF MEDICINAL CHEMISTRY

3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein Degradation

(2018) Andrea Testa et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

(2018) Lara N. Gechijian 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

New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons

(2018) Lucia Wang et al.   ACS Medicinal Chemistry Letters

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

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

Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity

(2018) Jinlei Bian et al.   BIOORGANIC CHEMISTRY

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

(2018) Hong Chen et al.   BIOORGANIC CHEMISTRY

Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation

(2018) Katerina Cermakova et al.   MOLECULES

Protein degradation: a validated therapeutic strategy with exciting prospects

(2017) Honorine Lebraud et al.   Essays in Biochemistry

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

Inducing Protein Degradation as a Therapeutic Strategy

(2017) Craig M. Crews   JOURNAL OF MEDICINAL 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

A “Click Chemistry Platform” for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation

(2017) Ryan P. Wurz et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals)

(2017) Matthias Schiedel 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

Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells

(2017) D T Saenz et al.   LEUKEMIA

BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells

(2017) B Sun et al.   LEUKEMIA

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation

(2017) Calla M Olson et al.   Nature Chemical Biology

Targeted protein degradation by PROTACs

(2017) Taavi K. Neklesa et al.   PHARMACOLOGY & THERAPEUTICS

Waste disposal—An attractive strategy for cancer therapy

(2017) Jemilat Salami et al.   SCIENCE

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

Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand

(2016) Yosuke Demizu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy

(2016) Nobumichi Ohoka et al.   CURRENT CANCER DRUG TARGETS

Chemical genetics approaches for selective intervention in epigenetics

(2016) Andrew C Runcie et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Inhibition of bromodomain and extra-terminal (BET) proteins increases NKG2D ligand MICA expression and sensitivity to NK cell-mediated cytotoxicity in multiple myeloma cells: role of cMYC-IRF4-miR-125b interplay

(2016) Maria Pia Abruzzese et al.   Journal of Hematology & Oncology

Degradation of Akt using protein-catalyzed capture agents

(2016) Ryan K. Henning et al.   JOURNAL OF PEPTIDE SCIENCE

Targeted Degradation of Proteins Localized in Subcellular Compartments by Hybrid Small Molecules

(2016) Keiichiro Okuhira et al.   MOLECULAR PHARMACOLOGY

Induced protein degradation: an emerging drug discovery paradigm

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

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

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

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

Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus

(2014) Kristopher Montrose et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Rapid and reversible knockdown of endogenous proteins by peptide-directed lysosomal degradation

(2014) Xuelai Fan et al.   NATURE NEUROSCIENCE

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

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

Development of target protein-selective degradation inducer for protein knockdown

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

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

(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

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

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

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

Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein

(2010) Peter O Bauer et al.   NATURE BIOTECHNOLOGY

Protacs for Treatment of Cancer

(2010) Kathleen M Sakamoto   PEDIATRIC RESEARCH

Design and Applications of Bifunctional Small Molecules: Why Two Heads Are Better Than One

(2008) Timothy W. Corson et al.   ACS Chemical Biology

Chimeric molecules facilitate the degradation of androgen receptors and repress the growth of LNCaP cells

(2008) Yue-Qing Tang et al.   ASIAN JOURNAL OF ANDROLOGY

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

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

Development of an Aryl Hydrocarbon Receptor Antagonist Using the Proteolysis-Targeting Chimeric Molecules Approach: A Potential Tool for Chemoprevention

(2008) D. Puppala et al.   MOLECULAR PHARMACOLOGY

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

(2008) A Rodriguez-Gonzalez et al.   ONCOGENE

hSef potentiates EGF-mediated MAPK signaling through affecting EGFR trafficking and degradation

(2007) Yongming Ren et al.   CELLULAR SIGNALLING