The state of the art of PROTAC technologies for drug discovery

PROTAC targeted protein degraders: the past is prologue

(2022) Miklós Békés et al.   NATURE REVIEWS DRUG DISCOVERY

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

Antivirals with common targets against highly pathogenic viruses

(2021) Lu Lu et al.   CELL

Cancer Selective Target Degradation by Folate-Caged PROTACs

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

LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation

(2021) Green Ahn et al.   Nature Chemical Biology

Targeted protein degraders crowd into the clinic

(2021) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy

(2021) Chi Zhang et al.   Nature Communications

Research progress of MEK1/2 inhibitors and degraders in the treatment of cancer

(2021) Chao Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

TF-PROTACs Enable Targeted Degradation of Transcription Factors

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

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

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

bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA)

(2020) Shuhui Lim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

(2020) Steven Kregel et al.   NEOPLASIA

Antibody–PROTAC Conjugates Enable HER2-Dependent Targeted Protein Degradation of BRD4

(2020) Marı́a Maneiro et al.   ACS Chemical Biology

How We Think about Targeting RNA with Small Molecules

(2020) Matthew G. Costales et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

PROTAC Compounds Targeting α-Synuclein Protein for Treating Neurogenerative Disorders: Alzheimer’s and Parkinson’s Diseases

(2020) Robert B. Kargbo   ACS Medicinal Chemistry Letters

Lysosome-targeting chimaeras for degradation of extracellular proteins

(2020) Steven M. Banik et al.   NATURE

The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K

(2020) Mikołaj Słabicki et al.   NATURE

Discovering Nature’s super glue

(2020) Zhi Zeng et al.   Nature Chemical Biology

Prospecting for molecular glues

(2020) Willem den Besten et al.   Nature Chemical Biology

Rational discovery of molecular glue degraders via scalable chemical profiling

(2020) Cristina Mayor-Ruiz et al.   Nature Chemical Biology

Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs

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

The therapeutic potential of PROTACs

(2020) Andrew B. Benowitz et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

PROTAC-DB: an online database of PROTACs

(2020) Gaoqi Weng et al.   NUCLEIC ACIDS RESEARCH

PhotoPROTACs: A Novel Biotechnology for Cancer Treatment

(2020) Zhi-wei Wang et al.   TRENDS IN CELL BIOLOGY

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

New Chemical Modalities Enabling Specific RNA Targeting and Degradation: Application to SARS-CoV-2 RNA

(2020) Audrey Di Giorgio et al.   ACS Central Science

Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development

(2020) Katherine A. Donovan et al.   CELL

PROTACs: New method to degrade transcription regulating proteins

(2020) Beichen Hu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges

(2020) Shenxin Zeng et al.   EUROPEAN 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

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

(2019) Yonghui Sun et al.   LEUKEMIA

PROTAC-Mediated Degradation of Bruton’s Tyrosine Kinase Is Inhibited by Covalent Binding

(2019) Christopher P. Tinworth et al.   ACS Chemical Biology

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

(2019) M Catarina Silva et al.   eLife

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

(2019) George M Burslem et al.   CANCER RESEARCH

Development of Multifunctional Histone Deacetylase 6 Degraders with Potent Antimyeloma Activity

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

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

Reversible Spatiotemporal Control of Induced Protein Degradation by Bistable PhotoPROTACs

(2019) Patrick Pfaff et al.   ACS Central Science

ATTEC: a potential new approach to target proteinopathies

(2019) Zhaoyang Li et al.   Autophagy

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

Light-Induced Protein Degradation with Photocaged PROTACs

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

Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15

(2019) Tabitha C. Ting et al.   Cell Reports

Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein

(2019) Haibin Zhou et al.   JOURNAL OF MEDICINAL CHEMISTRY

AUTACs: Cargo-Specific Degraders Using Selective Autophagy

(2019) Daiki Takahashi et al.   MOLECULAR CELL

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

(2018) Shanshan Gu et al.   BIOESSAYS

Small Molecule Targeted Recruitment of a Nuclease to RNA

(2018) Matthew G. Costales et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

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

Modulating PCAF/GCN5 Immune Cell Function through a PROTAC Approach

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

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

Impact of Target Warhead and Linkage Vector on Inducing Protein Degradation: Comparison of Bromodomain and Extra-Terminal (BET) Degraders Derived from Triazolodiazepine (JQ1) and Tetrahydroquinoline (I-BET726) BET Inhibitor Scaffolds

(2017) Kwok-Ho Chan 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

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

(2017) Ting Han et al.   SCIENCE

A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase

(2016) Mary E. Matyskiela et al.   NATURE

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

(2016) Georg Petzold et al.   NATURE

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

(2016) Honorine Lebraud et al.   ACS Central Science

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