Homobivalent, Trivalent, and Covalent PROTACs: Emerging Strategies for Protein Degradation

Efficient targeted oncogenic KRASG12C degradation via first reversible-covalent PROTAC

(2022) Fang Yang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Targeting the Non-Catalytic Functions: a New Paradigm for Kinase Drug Discovery?

(2022) Zhen Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications

(2022) Nathaniel J. Henning et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Strategies for designing proteolysis targeting chimaeras (PROTACs)

(2022) Shipeng He et al.   MEDICINAL RESEARCH REVIEWS

PROTAC targeted protein degraders: the past is prologue

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

Discovery of novel potent covalent inhibitor-based EGFR degrader with excellent in vivo efficacy

(2022) Shi Shi et al.   BIOORGANIC CHEMISTRY

Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands

(2022) Hong-Yi Zhao et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel CRBN-Recruiting Proteolysis-Targeting Chimeras as Degraders of Stimulator of Interferon Genes with In Vivo Anti-Inflammatory Efficacy

(2022) Jin Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Deubiquitinase-targeting chimeras for targeted protein stabilization

(2022) Nathaniel J. Henning et al.   Nature Chemical Biology

DUBTACs for targeted protein stabilization

(2022) Joseph Willson   NATURE REVIEWS DRUG DISCOVERY

Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope

(2022) Sinan Ma et al.   Acta Pharmaceutica Sinica B

Effective degradation of EGFRL858R+T790M mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems

(2021) Xiaojuan Qu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 1: Exploration of Antibody Linker, Payload Loading, and Payload Molecular Properties

(2021) Peter S. Dragovich et al.   JOURNAL OF MEDICINAL CHEMISTRY

Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy

(2021) Peter S. Dragovich et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cancer Selective Target Degradation by Folate-Caged PROTACs

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

DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras

(2021) Xiaoyu Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeted protein degraders crowd into the clinic

(2021) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

Aptamer‐PROTAC Conjugates (APCs) for Tumor‐Specific Targeting in Breast Cancer

(2021) Shipeng He et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Design and linkage optimization of ursane-thalidomide-based PROTACs and identification of their targeted-degradation properties to MDM2 protein

(2021) Zhiwen Qi et al.   BIOORGANIC CHEMISTRY

Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic

(2021) Zhenyi Hu et al.   CHEMBIOCHEM

The rise of covalent proteolysis targeting chimeras

(2021) Ronen Gabizon et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries

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

Rational Design and Synthesis of Novel Dual PROTACs for Simultaneous Degradation of EGFR and PARP

(2021) Mengzhu Zheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Folate-Guided Protein Degradation by Immunomodulatory Imide Drug-Based Molecular Glues and Proteolysis Targeting Chimeras

(2021) He Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Unraveling the Role of Linker Design in Proteolysis Targeting Chimeras

(2021) Troy A. Bemis et al.   JOURNAL OF MEDICINAL CHEMISTRY

The PROTACtable genome

(2021) Melanie Schneider et al.   NATURE REVIEWS DRUG DISCOVERY

Design, Synthesis, and Evaluation of Trivalent PROTACs Having a Functionalization Site with Controlled Orientation

(2021) Yifan Huang et al.   BIOCONJUGATE CHEMISTRY

Structure-based molecular hybridization design of Keap1-Nrf2 inhibitors as novel protective agents of acute lung injury

(2021) Le Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

(2021) Satomi Imaide et al.   Nature Chemical Biology

Structure-guided bifunctional molecules hit a DEUBAD-lacking hRpn13 species upregulated in multiple myeloma

(2021) Xiuxiu Lu et al.   Nature Communications

A Fluorescent Probe for Rapid, High-Contrast Visualization of Folate-Receptor-Expressing Tumors In Vivo

(2020) Koji Numasawa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

(2020) George M. Burslem et al.   CELL

Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives

(2020) Yuan Fang et al.   Acta Pharmaceutica Sinica B

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

(2020) Marı́a Maneiro et al.   ACS Chemical Biology

Design and synthesis of selective degraders of EGFRL858R/T790M mutant

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

Efficient Targeted Degradation via Reversible and Irreversible Covalent PROTACs

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

Exploiting the folate receptor α in oncology

(2020) Mariana Scaranti et al.   Nature Reviews Clinical Oncology

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

(2020) Bingqi Tong et al.   ACS Chemical Biology

Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs

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

Radiosensitization of human pancreatic cancer by piperlongumine analogues

(2020) Hao Ma et al.   CHINESE CHEMICAL LETTERS

PRosettaC: Rosetta Based Modeling of PROTAC Mediated Ternary Complexes

(2020) Daniel Zaidman et al.   Journal of Chemical Information and Modeling

Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry

(2020) Wen-Hao Guo et al.   Nature Communications

Bardoxolone conjugation enables targeted protein degradation of BRD4

(2020) Bingqi Tong et al.   Scientific Reports

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

(2020) Shenxin Zeng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Homo-PROTAC mediated suicide of MDM2 to treat non-small cell lung cancer

(2020) Shipeng He et al.   Acta Pharmaceutica Sinica B

Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase

(2019) Blake E. Smith et al.   Nature Communications

Cereblon versus VHL: Hijacking E3 ligases against each other using PROTACs

(2019) Miriam Girardini et al.   BIOORGANIC & MEDICINAL CHEMISTRY

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

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

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

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

Rapid and Reversible Knockdown of Endogenously Tagged Endosomal Proteins via an Optimized HaloPROTAC Degrader

(2019) Hannah Tovell et al.   ACS Chemical Biology

Identification of New Small-Molecule Inducers of Estrogen-related Receptor α (ERRα) Degradation

(2019) Lijie Peng et al.   ACS Medicinal Chemistry Letters

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

(2019) Stefanie Lindner et al.   Jove-Journal of Visualized Experiments

Harnessing the anti-cancer natural product nimbolide for targeted protein degradation

(2019) Jessica N. Spradlin et al.   Nature Chemical Biology

Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16

(2019) Xiaoyu Zhang et al.   Nature Chemical Biology

Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations

(2019) Mélissanne de Wispelaere et al.   Nature Communications

Development of selective small molecule MDM2 degraders based on nutlin

(2019) Bo Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Simple Structural Modifications Converting a Bona Fide MDM2 PROTAC Degrader into a Molecular Glue Molecule: A Cautionary Tale in the Design of PROTAC Degraders

(2019) Jiuling Yang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Antibody Conjugation of a Chimeric BET Degrader Enables in vivo Activity

(2019) Thomas H. Pillow et al.   ChemMedChem

Aptamers: A Review of Their Chemical Properties and Modifications for Therapeutic Application

(2019) Adachi et al.   MOLECULES

Targeted protein degradation: expanding the toolbox

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

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

(2019) Yahui Huang et al.   Acta Pharmaceutica Sinica B

Antibody-mediated delivery of chimeric protein degraders which target estrogen receptor alpha (ERα)

(2019) Peter S. Dragovich et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders

(2018) Mette Ishoey et al.   ACS Chemical Biology

Oxidation resistance 1 is a novel senolytic target

(2018) Xin Zhang et al.   AGING CELL

High-Throughput Cysteine Scanning To Identify Stable Antibody Conjugation Sites for Maleimide- and Disulfide-Based Linkers

(2018) Rachana Ohri et al.   BIOCONJUGATE CHEMISTRY

An Anti-CLL-1 Antibody-Drug Conjugate for the Treatment of Acute Myeloid Leukemia

(2018) Bing Zheng et al.   CLINICAL CANCER 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

Homo-PROTACs for the Chemical Knockdown of Cereblon

(2018) Christian Steinebach et al.   ACS Chemical Biology

Targeting STING with covalent small-molecule inhibitors

(2018) Simone M. Haag et al.   NATURE

Targeted Degradation of MDM2 as a New Approach to Improve the Efficacy of MDM2-p53 Inhibitors

(2018) Ryan P. Wurz 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

TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression

(2018) Ka-wing Fong et al.   Nature Communications

Small molecule-drug conjugates: A novel strategy for cancer-targeted treatment

(2018) Chunlin Zhuang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structural basis of PROTAC cooperative recognition for selective protein degradation

(2017) Morgan S Gadd et al.   Nature Chemical Biology

Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

(2017) Chiara Maniaci et al.   Nature Communications

Small-Molecule PROTACS: New Approaches to Protein Degradation

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

Efficient protein knockdown of HaloTag-fused proteins using hybrid molecules consisting of IAP antagonist and HaloTag ligand

(2016) Shusuke Tomoshige et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Aptamers as targeted therapeutics: current potential and challenges

(2016) Jiehua Zhou 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

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

Small-Molecule Inhibitors of the MDM2–p53 Protein–Protein Interaction (MDM2 Inhibitors) in Clinical Trials for Cancer Treatment

(2014) Yujun Zhao et al.   JOURNAL OF MEDICINAL CHEMISTRY

MDM2 Small-Molecule Antagonist RG7112 Activates p53 Signaling and Regresses Human Tumors in Preclinical Cancer Models

(2013) C. Tovar et al.   CANCER RESEARCH

Discovery, Synthesis, and Biological Evaluation of Orally Active Pyrrolidone Derivatives as Novel Inhibitors of p53–MDM2 Protein–Protein Interaction

(2012) Chunlin Zhuang et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

The resurgence of covalent drugs

(2011) Juswinder Singh et al.   NATURE REVIEWS DRUG DISCOVERY

Two-Headed PROTAC: An Effective New Tool for Targeted Protein Degradation

(2010) Kedra Cyrus  et al.   CHEMBIOCHEM

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