Opportunities and Challenges of Small Molecule Induced Targeted Protein Degradation

Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy

(2021) Liguo Wang et al.   Nature Chemical Biology

Mutant-selective degradation by BRAF-targeting PROTACs

(2021) Shanique Alabi et al.   Nature Communications

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

(2020) George M. Burslem et al.   CELL

Optical Control of Small Molecule-Induced Protein Degradation

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

Light-induced control of protein destruction by opto-PROTAC

(2020) Jing Liu et al.   Science Advances

PHOTACs enable optical control of protein degradation

(2020) Martin Reynders et al.   Science Advances

Discovery of Selective Small Molecule Degraders of BRAF-V600E

(2020) Xiao-Ran Han et al.   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

Degradation versus Inhibition: Development of Proteolysis-Targeting Chimeras for Overcoming Statin-Induced Compensatory Upregulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase

(2020) Mei-Xin Li et al.   JOURNAL OF MEDICINAL CHEMISTRY

PROTAC Technology: Opportunities and Challenges

(2020) Hongying Gao et al.   ACS Medicinal Chemistry Letters

Development of Selective Histone Deacetylase 6 (HDAC6) Degraders Recruiting Von Hippel–Lindau (VHL) E3 Ubiquitin Ligase

(2020) Ka Yang et al.   ACS Medicinal Chemistry Letters

FAK-targeting PROTAC as a chemical tool for the investigation of non-enzymatic FAK function in mice

(2020) Hongying Gao et al.   Protein & Cell

Challenges of in vitro genome editing with CRISPR/Cas9 and possible solutions: A review

(2020) Vida Ebrahimi et al.   GENE

Global PROTAC Toolbox for Degrading BCR–ABL Overcomes Drug-Resistant Mutants and Adverse Effects

(2020) Yiqing Yang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Functional characterization of a PROTAC directed against BRAF mutant V600E

(2020) Ganna Posternak et al.   Nature Chemical Biology

Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs

(2020) Michael J. Bond et al.   ACS Central Science

PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase

(2020) Bikash Adhikari et al.   Nature Chemical Biology

The PROTAC technology in drug development

(2019) Yutian Zou et al.   CELL BIOCHEMISTRY AND FUNCTION

Developing potent PROTACs tools for selective degradation of HDAC6 protein

(2019) Zixuan An et al.   Protein & Cell

A chemical approach for global protein knockdown from mice to non-human primates

(2019) Xiuyun Sun et al.   Cell Discovery

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

(2019) Yonghui Sun et al.   LEUKEMIA

Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions

(2019) Johannes Popow et al.   JOURNAL OF MEDICINAL CHEMISTRY

Photoactivatable Prodrug of Doxazolidine Targeting Exosomes

(2019) Ryo Tamura et al.   JOURNAL OF MEDICINAL CHEMISTRY

ARV-110: An oral androgen receptor PROTAC degrader for prostate cancer.

(2019) Taavi Neklesa et al.   JOURNAL OF CLINICAL ONCOLOGY

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

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

KRASG12C inhibitors on the horizon

(2019) Ali Cagir et al.   Future Medicinal Chemistry

Development of Multifunctional Histone Deacetylase 6 Degraders with Potent Antimyeloma Activity

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

Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders

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

Reversible Spatiotemporal Control of Induced Protein Degradation by Bistable PhotoPROTACs

(2019) Patrick Pfaff et al.   ACS Central Science

PROTACs as Potential Therapeutic Agents for Cancer Drug Resistance

(2019) Xiuyun Sun et al.   BIOCHEMISTRY

A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo

(2019) Longchuan Bai et al.   CANCER CELL

Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel–Lindau (VHL) E3 Ubiquitin Ligase

(2019) Quanju Zhao et al.   JOURNAL OF MEDICINAL CHEMISTRY

Light-Induced Protein Degradation with Photocaged PROTACs

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

Design, Synthesis, and Evaluation of Highly Potent FAK-Targeting PROTACs

(2019) Hongying Gao et al.   ACS Medicinal Chemistry Letters

The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients

(2019) Jill Hallin et al.   Cancer Discovery

Design, synthesis and biological evaluation of Proteolysis Targeting Chimeras (PROTACs) as a BTK degraders with improved pharmacokinetic properties

(2019) Saul Jaime-Figueroa et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Targeting the C481S Ibrutinib-Resistance Mutation in Bruton’s Tyrosine Kinase Using PROTAC-Mediated Degradation

(2018) Alexandru D. Buhimschi et al.   BIOCHEMISTRY

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

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

Ubiquitin-dependent degradation of CDK2 drives the therapeutic differentiation of AML by targeting PRDX2

(2018) Meidan Ying et al.   BLOOD

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

Current Insights of BRAF Inhibitors in Cancer

(2018) Bogos Agianian et al.   JOURNAL OF MEDICINAL CHEMISTRY

The dTAG system for immediate and target-specific protein degradation

(2018) Behnam Nabet 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

Bruton's Tyrosine Kinase degradation as a therapeutic strategy for cancer

(2018) Dennis Dobrovolsky et al.   BLOOD

Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway

(2018) Zhiqiang Li et al.   CANCER CELL

Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: An Update

(2018) Solomon Tadesse et al.   JOURNAL OF MEDICINAL CHEMISTRY

Addressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation

(2018) Philipp M. Cromm et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Optogenetic control of kinetochore function

(2017) Huaiying Zhang et al.   Nature Chemical Biology

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

Small-Molecule PROTACS: New Approaches to Protein Degradation

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

The Role of New Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

(2016) Priyanka A. Pophali et al.   CANCER JOURNAL

Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view

(2016) Shaoyong Lu et al.   CHEMICAL SOCIETY REVIEWS

Structural insights into HDAC6 tubulin deacetylation and its selective inhibition

(2016) Yasuyuki Miyake et al.   Nature Chemical Biology

A MYC–aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer

(2016) Daniel Dauch et al.   NATURE MEDICINE

Induced protein degradation: an emerging drug discovery paradigm

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

Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence

(2016) C Yang et al.   ONCOGENE

Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype

(2016) Feimeng Zheng et al.   Nature Communications

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

Hybrid pyrimidine alkynyls inhibit the clinically resistance related Bcr-AblT315I mutant

(2015) Xiaoyun Lu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Targeting CDK6 in cancer: State of the art and new insights

(2015) Solomon Tadesse et al.   CELL CYCLE

Wavelength-selective cleavage of photoprotecting groups: strategies and applications in dynamic systems

(2015) Mickel J. Hansen et al.   CHEMICAL SOCIETY REVIEWS

Mechanisms of resistance to BCR–ABL TKIs and the therapeutic strategies: A review

(2015) Ke Yang et al.   CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma

(2015) Ruben Niesvizky et al.   LEUKEMIA & LYMPHOMA

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

FAK dimerization controls its kinase-dependent functions at focal adhesions

(2014) K. Brami-Cherrier et al.   EMBO JOURNAL

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

Functional characterization of BTK C481S mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors

(2014) S Cheng et al.   LEUKEMIA

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

(2014) Eric S. Fischer et al.   NATURE

How to control proteins with light in living systems

(2014) Arnaud Gautier et al.   Nature Chemical Biology

Targeting RAS–ERK signalling in cancer: promises and challenges

(2014) Ahmed A. Samatar et al.   NATURE REVIEWS DRUG DISCOVERY

Drugging the HDAC6–HSP90 interplay in malignant cells

(2014) Oliver H. Krämer et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Cell-Cycle Reprogramming for PI3K Inhibition Overrides a Relapse-Specific C481S BTK Mutation Revealed by Longitudinal Functional Genomics in Mantle Cell Lymphoma

(2014) D. Chiron et al.   Cancer Discovery

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

Small Molecule Inhibitors of Aurora-A Induce Proteasomal Degradation of N-Myc in Childhood Neuroblastoma

(2013) Markus Brockmann et al.   CANCER CELL

Reversible Photocontrol of Biological Systems by the Incorporation of Molecular Photoswitches

(2013) Wiktor Szymański et al.   CHEMICAL REVIEWS

HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs?

(2013) Claudia Simões-Pires et al.   Molecular Neurodegeneration

Tumor adaptation and resistance to RAF inhibitors

(2013) Piro Lito et al.   NATURE MEDICINE

Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma

(2013) Michael L. Wang et al.   NEW ENGLAND JOURNAL OF MEDICINE

PD-0332991, a CDK4/6 Inhibitor, Significantly Prolongs Survival in a Genetically Engineered Mouse Model of Brainstem Glioma

(2013) Kelly L. Barton et al.   PLoS One

Light-Controlled Tools

(2012) Clara Brieke et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma

(2012) J. P. Leonard et al.   BLOOD

Atorvastatin in Pulmonary Arterial Hypertension (APATH) study

(2012) Wei-Jie Zeng et al.   EUROPEAN RESPIRATORY JOURNAL

The Ras protein superfamily: Evolutionary tree and role of conserved amino acids

(2012) Ana Maria Rojas et al.   JOURNAL OF CELL BIOLOGY

Selective Histone Deacetylase 6 Inhibitors Bearing Substituted Urea Linkers Inhibit Melanoma Cell Growth

(2012) Joel A. Bergman et al.   JOURNAL OF MEDICINAL CHEMISTRY

A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing

(2012) Linda Madisen et al.   NATURE NEUROSCIENCE

Vemurafenib: the first drug approved for BRAF-mutant cancer

(2012) Gideon Bollag et al.   NATURE REVIEWS DRUG DISCOVERY

Focal adhesion kinase is required for KSHV vGPCR signaling

(2011) Meilan He et al.   MOLECULAR CARCINOGENESIS

A kinase-independent role for Aurora A in the assembly of mitotic spindle microtubules in Caenorhabditis elegans embryos

(2011) Mika Toya et al.   NATURE 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

Dysregulation of the mevalonate pathway promotes transformation

(2010) J. W. Clendening et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Stabilization of N-Myc Is a Critical Function of Aurora A in Human Neuroblastoma

(2009) Tobias Otto et al.   CANCER CELL

The Role of HMGCR Alternative Splicing in Statin Efficacy

(2009) Marisa Wong Medina et al.   TRENDS IN CARDIOVASCULAR MEDICINE

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

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

Photoresponsive Surfaces with Two Independent Wavelength-Selective Functional Levels

(2008) Petra Stegmaier et al.   LANGMUIR