Progress on small-molecule proteolysis-targeting chimeras

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

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

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

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

(2018) Lara N. Gechijian et al.   Nature Chemical Biology

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

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

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

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 Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment

(2017) Georg E. Winter et al.   MOLECULAR CELL

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation

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

Structural basis of PROTAC cooperative recognition for selective protein degradation

(2017) Morgan S Gadd 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

Targeting ALK: Precision Medicine Takes on Drug Resistance

(2017) Jessica J. Lin et al.   Cancer Discovery

Small-Molecule PROTACS: New Approaches to Protein Degradation

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

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

Cyclin Dependent Kinase 9 Inhibitors for Cancer Therapy

(2016) Yogesh A. Sonawane et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase

(2016) Georg Petzold et al.   NATURE

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

(2016) Anja F Hohmann et al.   Nature Chemical Biology

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

HaloTag Technology: A Versatile Platform for Biomedical Applications

(2015) Christopher G. England et al.   BIOCONJUGATE CHEMISTRY

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer

(2015) J. A. Beaver et al.   CLINICAL CANCER RESEARCH

Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF

(2015) James Bennett et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor

(2015) Wylie S. Palmer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Design of γ-Carboline Analogues as Potent and Specific BET Bromodomain Inhibitors

(2015) Xu Ran et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2015) Jan Krönke et al.   NATURE

Prime time for PROTACs

(2015) Raymond J Deshaies   Nature Chemical Biology

Catalytic in vivo protein knockdown by small-molecule PROTACs

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

Selectively targeting proteins for degradation

(2015) Sarah Crunkhorn   NATURE REVIEWS DRUG DISCOVERY

The unravelling of the ubiquitin system

(2015) Aaron Ciechanover   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

The demographics of the ubiquitin system

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

A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production

(2015) Ueli Nachbur et al.   Nature Communications

Small-Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System

(2014) Dennis L. Buckley et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

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

TRIM24 Is a p53-Induced E3-Ubiquitin Ligase That Undergoes ATM-Mediated Phosphorylation and Autodegradation during DNA Damage

(2014) A. K. Jain et al.   MOLECULAR AND CELLULAR BIOLOGY

The Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition

(2014) Junwei Shi et al.   MOLECULAR CELL

Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib

(2014) Jennifer A. Woyach et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

Bruton's tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL)

(2013) J. A. Woyach et al.   BLOOD

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

Aurora A kinase and its substrate TACC3 are required for central spindle assembly

(2013) Antonios Lioutas et al.   EMBO REPORTS

Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia

(2013) John C. Byrd et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

Mitotic catastrophe and cell death induced by depletion of centrosomal proteins

(2013) M Kimura et al.   Cell Death & Disease

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

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

Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide

(2012) A Lopez-Girona et al.   LEUKEMIA

BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia

(2012) Oliver Hantschel et al.   Nature Chemical Biology

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

A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging

(2011) Daniel G Booth et al.   EMBO JOURNAL

Estrogen related receptors (ERRs): A new dawn in transcriptional control of mitochondrial gene networks

(2011) Lillian J. Eichner et al.   MITOCHONDRION

Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability

(2010) Chiou-Hong Lin et al.   JOURNAL OF CELL 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

Impact of linker length on the activity of PROTACs

(2010) Kedra Cyrus et al.   Molecular BioSystems

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors

(2010) Young Lim Choi et al.   NEW ENGLAND JOURNAL OF MEDICINE

The centrosomal protein TACC3 controls paclitaxel sensitivity by modulating a premature senescence program

(2010) S Schmidt et al.   ONCOGENE

A small molecule accelerates neuronal differentiation in the adult rat

(2010) H. Wurdak et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

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

Trim24 targets endogenous p53 for degradation

(2009) Kendra Allton et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

HaloTag: A Novel Protein Labeling Technology for Cell Imaging and Protein Analysis

(2008) Georgyi V. Los et al.   ACS Chemical Biology

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

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

Molecular biology of bcr-abl1-positive chronic myeloid leukemia

(2008) A. Quintas-Cardama et al.   BLOOD

Transcriptional Control of Energy Homeostasis by the Estrogen-Related Receptors

(2008) Vincent Giguère   ENDOCRINE REVIEWS

Small Molecules Destabilize cIAP1 by Activating Auto-ubiquitylation

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