Proteolysis-targeting chimeras (PROTACs) in cancer therapy

Development of Antibody-Based PROTACs for the Degradation of the Cell-Surface Immune Checkpoint Protein PD-L1

(2021) Adam D. Cotton et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Discovery of a PROTAC targeting ALK with in vivo activity

(2021) Guoyi Yan et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide

(2021) Max Jan et al.   Nature Reviews Clinical Oncology

Targeted protein degraders crowd into the clinic

(2021) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

From Conception to Development: Investigating PROTACs Features for Improved Cell Permeability and Successful Protein Degradation

(2021) Carlotta Cecchini et al.   Frontiers in Chemistry

TF-PROTACs Enable Targeted Degradation of Transcription Factors

(2021) Jing Liu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

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

Selective inhibition of Ph-positive ALL cell growth through kinase-dependent and independent effects by CDK6-specific PROTACs

(2020) Marco De Dominici et al.   BLOOD

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

(2020) George M. Burslem et al.   CELL

Development of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance

(2020) Ning Sun et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design and synthesis of α-naphthoflavone chimera derivatives able to eliminate cytochrome P450 (CYP)1B1-mediated drug resistance via targeted CYP1B1 degradation

(2020) Li Zhou et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC)

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

Discovery of Potent and Selective Epidermal Growth Factor Receptor (EGFR) Bifunctional Small-Molecule Degraders

(2020) Meng Cheng 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

Harnessing the Power of Proteolysis for Targeted Protein Inactivation

(2020) Rati Verma et al.   MOLECULAR CELL

CRISPR-engineered T cells in patients with refractory cancer

(2020) Edward A. Stadtmauer et al.   SCIENCE

U1 snRNP regulates cancer cell migration and invasion in vitro

(2020) Jung-Min Oh et al.   Nature Communications

Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment

(2020) Steven Kregel et al.   NEOPLASIA

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 the first potent proteolysis targeting chimera (PROTAC) degrader of indoleamine 2, 3-dioxygenase 1

(2020) Mingxing Hu et al.   Acta Pharmaceutica Sinica B

First small-molecule PROTACs for G protein-coupled receptors: Inducing α1A-adrenergic receptor degradation

(2020) Zhenzhen Li et al.   Acta Pharmaceutica Sinica B

Bi-directional differentiation of single bronchioalveolar stem cells during lung repair

(2020) Kuo Liu et al.   Cell Discovery

Development of CDK2 and CDK5 Dual Degrader TMX‐2172

(2020) Nathanael Schiander Gray et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Mechanisms of Sensitivity and Resistance to CDK4/6 Inhibition

(2020) Mónica Álvarez-Fernández et al.   CANCER CELL

Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity

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

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

Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein

(2020) Mingliang Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeted Degradation of the Oncogenic MicroRNA 17-92 Cluster by Structure-Targeting Ligands

(2020) Xiaohui Liu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Efficient Targeted Degradation via Reversible and Irreversible Covalent PROTACs

(2020) Ronen Gabizon et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Small molecules, big impact: 20 years of targeted therapy in oncology

(2020) Philippe L Bedard et al.   LANCET

Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src

(2020) Sudhakar Manda et al.   MOLECULES

Targeting apoptosis in cancer therapy

(2020) Benedito A. Carneiro et al.   Nature Reviews Clinical Oncology

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

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

(2020) Bingqi Tong et al.   ACS Chemical Biology

Structural Insights into PROTAC-Mediated Degradation of Bcl-xL

(2020) Chun-wa Chung et al.   ACS Chemical Biology

Hydroxamic Acids Immobilized on Resins (HAIRs): A Toolbox for the Synthesis of Dual‐Targeting HDAC Inhibitors and HDAC Degraders (PROTACs)

(2020) Laura Sinatra et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Development of small-molecule BRD4 degraders based on pyrrolopyridone derivative

(2020) Jian Zhang et al.   BIOORGANIC CHEMISTRY

Discovery of novel resorcinol diphenyl ether-based PROTAC-like molecules as dual inhibitors and degraders of PD-L1

(2020) Binbin Cheng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

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

Discovery of First-in-class Protein Arginine Methyltransferase 5 (PRMT5) Degraders

(2020) Yudao Shen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Novel PDEδ Degraders for the Treatment of KRAS Mutant Colorectal Cancer

(2020) Junfei Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

Lysosome-targeting chimaeras for degradation of extracellular proteins

(2020) Steven M. Banik et al.   NATURE

Functional characterization of a PROTAC directed against BRAF mutant V600E

(2020) Ganna Posternak et al.   Nature Chemical Biology

Understanding and Improving the Membrane Permeability of VH032-Based PROTACs

(2020) Victoria G. Klein et al.   ACS Medicinal Chemistry Letters

Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs

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

Hematopoietic Progenitor Kinase1 (HPK1) Mediates T Cell Dysfunction and Is a Druggable Target for T Cell-Based Immunotherapies

(2020) Jingwen Si et al.   CANCER CELL

Optimal linker length for small molecule PROTACs that selectively target p38α and p38β for degradation

(2020) Craig Donoghue et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Designing an eEF2K-Targeting PROTAC small molecule that induces apoptosis in MDA-MB-231 cells

(2020) Yao Liu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo

(2020) Mingming Wei et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Progress in the Development of Small Molecular Inhibitors of Focal Adhesion Kinase (FAK)

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

Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders

(2020) Liqun Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of SK-575 as a Highly Potent and Efficacious Proteolysis-Targeting Chimera Degrader of PARP1 for Treating Cancers

(2020) Chaoguo Cao et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2020) Bikash Adhikari et al.   Nature Chemical Biology

Poly(ADP-ribose) polymerase inhibition: past, present and future

(2020) Nicola J. Curtin et al.   NATURE REVIEWS DRUG DISCOVERY

Targeting the SARS-CoV-2 RNA Genome with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders

(2020) Hafeez S. Haniff et al.   ACS Central Science

RNA‐PROTACs: Degraders of RNA‐Binding Proteins

(2020) Alice Ghidini et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Targeted degradation of CD147 proteins in melanoma

(2020) Zhe Zhou et al.   BIOORGANIC CHEMISTRY

Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development

(2020) Katherine A. Donovan et al.   CELL

Design and characterization of cereblon-mediated androgen receptor proteolysis-targeting chimeras

(2020) Akshay D. Takwale et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of potent small molecule PROTACs targeting mutant EGFR

(2020) Hong-Yi Zhao et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Potent and Selective Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Heterobifunctional Small-molecule Degraders

(2020) Jianping Hu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Effects of MTX-23, a Novel PROTAC of Androgen Receptor Splice Variant-7 and Androgen Receptor, on CRPC resistant to Second-Line Antiandrogen Therapy

(2020) Geun Taek Lee et al.   MOLECULAR CANCER THERAPEUTICS

Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes

(2020) James Schiemer et al.   Nature Chemical Biology

Recent developments in bioorthogonal chemistry and the orthogonality within

(2020) Mike L.W.J. Smeenk et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Discovery of selective CDK9 degraders with enhancing antiproliferative activity through PROTAC conversion

(2020) Xiaqiu Qiu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

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

The proteostasis network and its decline in ageing

(2019) Mark S. Hipp et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

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

Light-triggered release of photocaged therapeutics - Where are we now?

(2019) Joana M. Silva et al.   JOURNAL OF CONTROLLED RELEASE

Randomized Phase III Study of Alisertib or Investigator’s Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma

(2019) Owen A. O’Connor et al.   JOURNAL OF CLINICAL ONCOLOGY

Synthesis of 7-benzylguanosine cap-analogue conjugates for eIF4E targeted degradation

(2019) Tanpreet Kaur et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

VEGF in Signaling and Disease: Beyond Discovery and Development

(2019) Rajendra S. Apte et al.   CELL

Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance

(2019) Jonathan Cooper et al.   CANCER CELL

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

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

Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications

(2019) Carl C. Ward et al.   ACS Chemical Biology

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

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

Development and preclinical validation of a novel covalent ubiquitin receptor Rpn13 degrader in multiple myeloma

(2019) Yan Song et al.   LEUKEMIA

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

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

(2019) Hong Chen et al.   BIOORGANIC CHEMISTRY

Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-mediated Targeted Protein Degradation

(2019) George M Burslem et al.   CANCER RESEARCH

Targeted protein degradation: elements of PROTAC design

(2019) Stacey-Lynn Paiva et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

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

Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma

(2019) Neeraj Jain et al.   Science Translational Medicine

Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader

(2019) Hannah Tovell et al.   ACS Chemical Biology

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

Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1/Bcl-2 Derived from Nonselective Target Binding Ligands

(2019) Ziqian Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

TrkC-Targeted Kinase Inhibitors And PROTACs

(2019) Bosheng Zhao et al.   MOLECULAR PHARMACEUTICS

Development of targeted protein degradation therapeutics

(2019) Philip P. Chamberlain et al.   Nature Chemical Biology

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

Protein targeting chimeric molecules specific for dual bromodomain 4 (BRD4) and Polo-like kinase 1 (PLK1) proteins in acute myeloid leukemia cells

(2019) Xupeng Mu et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

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

Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader

(2019) Jieli Wei et al.   JOURNAL OF MEDICINAL CHEMISTRY

Light-Induced Protein Degradation with Photocaged PROTACs

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

Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds

(2019) Zhaoyang Li et al.   NATURE

Uncoupling of PARP1 trapping and inhibition using selective PARP1 degradation

(2019) Shuai Wang et al.   Nature Chemical Biology

Targeted protein degradation: expanding the toolbox

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

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

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

A novel strategy to block mitotic progression for targeted therapy

(2019) Junlong (Jack) Chi et al.   EBioMedicine

Structure-Based Design of a Macrocyclic PROTAC

(2019) Andrea Testa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Development of a PDEδ-Targeting PROTACs that Impair Lipid Metabolism

(2019) Michael Winzker et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Development of selective mono or dual PROTAC degrader probe of CDK isoforms

(2019) Fei Zhou et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Development of cell-permeable peptide-based PROTACs targeting estrogen receptor α

(2019) Yuxuan Dai et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands

(2019) Xin Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design, Synthesis, and Biological Evaluation of MEK PROTACs

(2019) Stefan Vollmer et al.   JOURNAL OF MEDICINAL CHEMISTRY

AUTACs: Cargo-Specific Degraders Using Selective Autophagy

(2019) Daiki Takahashi et al.   MOLECULAR CELL

A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity

(2019) Sajid Khan et al.   NATURE MEDICINE

Structure and Function of the 26S Proteasome

(2018) Jared A.M. Bard et al.   Annual Review of 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

In Vivo Photopharmacology

(2018) Katharina Hüll et al.   CHEMICAL REVIEWS

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

Regulation and Function of the PD-L1 Checkpoint

(2018) Chong Sun et al.   IMMUNITY

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

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

The dTAG system for immediate and target-specific protein degradation

(2018) Behnam Nabet et al.   Nature Chemical Biology

Plasticity in binding confers selectivity in ligand-induced protein degradation

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

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

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

Targeting the IL-6/JAK/STAT3 signalling axis in cancer

(2018) Daniel E. Johnson et al.   Nature Reviews Clinical Oncology

The promise and challenges of immune agonist antibody development in cancer

(2018) Patrick A. Mayes et al.   NATURE REVIEWS DRUG DISCOVERY

EMT: Mechanisms and therapeutic implications

(2018) Mohini Singh et al.   PHARMACOLOGY & THERAPEUTICS

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

Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of CDK8

(2018) John M. Hatcher et al.   ACS Medicinal Chemistry Letters

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

CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest

(2018) Shom Goel et al.   TRENDS IN CELL BIOLOGY

Development of a Novel B-Cell Lymphoma 6 (BCL6) PROTAC To Provide Insight into Small Molecule Targeting of BCL6

(2018) William McCoull et al.   ACS Chemical Biology

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

(2018) Dennis Dobrovolsky et al.   BLOOD

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

Enhancing Antiproliferative Activity and Selectivity of a FLT-3 Inhibitor by Proteolysis Targeting Chimera Conversion

(2018) George M. Burslem et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

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

Cancer immunoediting and resistance to T cell-based immunotherapy

(2018) Jake S. O’Donnell et al.   Nature Reviews Clinical Oncology

Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN

(2018) Quinlan L. Sievers et al.   SCIENCE

Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol

(2018) Shi-You Jiang et al.   Nature Communications

Double-slit photoelectron interference in strong-field ionization of the neon dimer

(2018) Maksim Kunitski et al.   Nature Communications

Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma

(2018) Gerard L Brien et al.   eLife

SG formation relies on eIF4GI-G3BP interaction which is targeted by picornavirus stress antagonists

(2018) Xiaodan Yang et al.   Cell Discovery

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

How Big Is Too Big for Cell Permeability?

(2017) Pär Matsson et al.   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

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

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

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

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

Transcription control by the ENL YEATS domain in acute leukaemia

(2017) Michael A. Erb et al.   NATURE

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

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

(2016) Xin Wang et al.   BIOCHEMICAL PHARMACOLOGY

A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase

(2016) Mary E. Matyskiela et al.   NATURE

The increasing complexity of the ubiquitin code

(2016) Richard Yau et al.   NATURE CELL BIOLOGY

Treating cancer with selective CDK4/6 inhibitors

(2016) Ben O'Leary et al.   Nature Reviews Clinical Oncology

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

Catalytic in vivo protein knockdown by small-molecule PROTACs

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

Kinase inhibitors and monoclonal antibodies in oncology: clinical implications

(2015) Helen Gharwan et al.   Nature Reviews Clinical Oncology

Clinical experiences with systemically administered siRNA-based therapeutics in cancer

(2015) Jonathan E. Zuckerman et al.   NATURE REVIEWS DRUG DISCOVERY

Regulation of RAF protein kinases in ERK signalling

(2015) Hugo Lavoie et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Degradation of HaloTag-fused nuclear proteins using bestatin-HaloTag ligand hybrid molecules

(2015) Shusuke Tomoshige et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

Immune evasion in cancer: Mechanistic basis and therapeutic strategies

(2015) Dass S. Vinay et al.   SEMINARS IN CANCER BIOLOGY

Broad targeting of resistance to apoptosis in cancer

(2015) Ramzi M. Mohammad et al.   SEMINARS IN CANCER BIOLOGY

Compensatory induction of MYC expression by sustained CDK9 inhibition via a BRD4-dependent mechanism

(2015) Huasong Lu et al.   eLife

Targeting RAS–ERK signalling in cancer: promises and challenges

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

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

Origins of Metastatic Traits

(2013) Sakari Vanharanta et al.   CANCER CELL

Reversible Photocontrol of Biological Systems by the Incorporation of Molecular Photoswitches

(2013) Wiktor Szymański et al.   CHEMICAL REVIEWS

The quest to overcome resistance to EGFR-targeted therapies in cancer

(2013) Curtis R Chong et al.   NATURE 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

Disrupting the Scaffold to Improve Focal Adhesion Kinase-Targeted Cancer Therapeutics

(2013) W. G. Cance et al.   Science Signaling

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

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

The Ubiquitin Code

(2012) David Komander et al.   Annual Review of Biochemistry

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

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

BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet

(2011) S. Soverini et al.   BLOOD

Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets

(2011) S. M. Schoenwaelder et al.   BLOOD

Mutant BRAF Melanomas—Dependence and Resistance

(2011) Poulikos I. Poulikakos et al.   CANCER CELL

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

(2011) Poulikos I. Poulikakos et al.   NATURE

Cancer Immunoediting: Integrating Immunity's Roles in Cancer Suppression and Promotion

(2011) R. D. Schreiber et al.   SCIENCE

Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity

(2010) Amie S. Corbin et al.   JOURNAL OF CLINICAL INVESTIGATION

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

Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation

(2010) Ramin Nazarian et al.   NATURE

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

Lin28 promotes transformation and is associated with advanced human malignancies

(2009) Srinivas R Viswanathan et al.   NATURE GENETICS

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

EGFR Antagonists in Cancer Treatment

(2008) Fortunato Ciardiello et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

(2008) A Rodriguez-Gonzalez et al.   ONCOGENE