Targeting reversible post-translational modifications with PROTACs: a focus on enzymes modifying protein lysine and arginine residues

Dissecting and targeting noncanonical functions of EZH2 in multiple myeloma via an EZH2 degrader

(2023) Xufen Yu et al.   ONCOGENE

Targeted MDM2 degradation reveals a new vulnerability for p53 inactivated triple negative breast cancer

(2023) Clare M. Adams et al.   Cancer Discovery

Targeted Degradation of PRC1 Components, BMI1 and RING1B, via a Novel Protein Complex Degrader Strategy

(2023) Kwang‐Su Park et al.   Advanced Science

PROTAC Linkerology Leads to an Optimized Bivalent Chemical Degrader of Polycomb Repressive Complex 2 (PRC2) Components

(2023) Frances M. Bashore et al.   ACS Chemical Biology

Heterobifunctional Ligase Recruiters Enable pan-Degradation of Inhibitor of Apoptosis Proteins

(2023) Yuen Lam Dora Ng et al.   Journal of Medicinal Chemistry

Discovery of highly potent HDAC8 PROTACs with anti-tumor activity

(2023) Chunlong Zhao et al.   BIOORGANIC CHEMISTRY

Selective degradation of PARP2 by PROTACs via recruiting DCAF16 for triple-negative breast cancer

(2022) Chunlan Pu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Optimization of Class I Histone Deacetylase PROTACs Reveals that HDAC1/2 Degradation is Critical to Induce Apoptosis and Cell Arrest in Cancer Cells

(2022) Joshua P. Smalley et al.   JOURNAL OF MEDICINAL CHEMISTRY

EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis

(2022) Jun Wang et al.   NATURE CELL BIOLOGY

Discovery of a Potent and Selective Degrader for USP7

(2022) Yuan Pei et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Comprehensive Transcriptomic Analysis of Novel Class I HDAC Proteolysis Targeting Chimeras (PROTACs)

(2022) India M. Baker et al.   BIOCHEMISTRY

Chemical biology and pharmacology of histone lysine methylation inhibitors

(2022) Samir H. Barghout et al.   Biochimica et Biophysica Acta-Gene Regulatory Mechanisms

Discovery of precision targeting EZH2 degraders for triple-negative breast cancer

(2022) Cheng Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design, Synthesis and Biological Characterization of Histone Deacetylase 8 (HDAC8) Proteolysis Targeting Chimeras (PROTACs) with Anti-Neuroblastoma Activity

(2022) Salma Darwish et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Discovery of a First-in-Class Degrader for Nuclear Receptor Binding SET Domain Protein 2 (NSD2) and Ikaros/Aiolos

(2022) Fanye Meng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of CN0 as a novel proteolysis-targeting chimera (PROTAC) degrader of PARP1 that can activate the cGAS/STING immunity pathway combined with daunorubicin

(2022) Shanshan Lin et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Synthesis and biological evaluation of a tumor-selective degrader of PARP1

(2022) Chunlan Pu et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery of pomalidomide-based PROTACs for selective degradation of histone deacetylase 8

(2022) Zhiqiang Sun et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a potent and selective proteolysis targeting chimera (PROTAC) degrader of NSD3 histone methyltransferase

(2022) Yaoliang Sun et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

An MDM2 degrader for treatment of acute leukemias

(2022) Bridget K. Marcellino et al.   LEUKEMIA

A cryptic transactivation domain of EZH2 binds AR and AR’s splice variant, promoting oncogene activation and tumorous transformation

(2022) Jun Wang et al.   NUCLEIC ACIDS RESEARCH

Selective PARP1 Inhibitors, PARP1-based Dual-Target Inhibitors, PROTAC PARP1 Degraders, and Prodrugs of PARP1 Inhibitors for Cancer Therapy

(2022) Xiaopeng Peng et al.   PHARMACOLOGICAL RESEARCH

A PARP1 PROTAC as a novel strategy against PARP inhibitor resistance via promotion of ferroptosis in p53-positive breast cancer

(2022) Ge Li et al.   BIOCHEMICAL PHARMACOLOGY

Design and characterization of PROTAC degraders specific to protein N-terminal methyltransferase 1

(2022) Qilong Zhou et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of pan-IAP degraders via a CRBN recruiting mechanism

(2022) Seulki Park et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Solid-Phase Synthesis of Cereblon-Recruiting Selective Histone Deacetylase 6 Degraders (HDAC6 PROTACs) with Antileukemic Activity

(2022) Laura Sinatra et al.   Journal of Medicinal Chemistry

Structure-Based Discovery of Selective Histone Deacetylase 8 Degraders with Potent Anticancer Activity

(2022) Jinbo Huang et al.   Journal of Medicinal Chemistry

Design and characterization of a heterobifunctional degrader of KEAP1

(2022) Hao Chen et al.   Redox Biology

Post-translational modifications: regulation of nitrogen utilization and signaling

(2021) Wei Wang et al.   PLANT AND CELL PHYSIOLOGY

Design and Synthesis of EZH2-Based PROTACs to Degrade the PRC2 Complex for Targeting the Noncatalytic Activity of EZH2

(2021) Zhihao Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeted Degradation of PARP14 Using a Heterobifunctional Small Molecule

(2021) Tim J. Wigle et al.   CHEMBIOCHEM

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

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

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

ADP‐ribosyltransferases, an update on function and nomenclature

(2021) Bernhard Lüscher et al.   FEBS Journal

Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma

(2021) Yalin Tu et al.   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

Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code

(2021) Yanfeng Wang et al.   Frontiers in Pharmacology

Attenuation of NLRP3 Inflammasome Activation by Indirubin-Derived PROTAC Targeting HDAC6

(2021) Zhuoxian Cao et al.   ACS Chemical Biology

Designing HDAC-PROTACs: lessons learned so far

(2021) Fabian Fischer et al.   Future Medicinal Chemistry

Cellular pathways influenced by protein arginine methylation: Implications for cancer

(2021) Jian Xu et al.   MOLECULAR CELL

dbPTM in 2022: an updated database for exploring regulatory networks and functional associations of protein post-translational modifications

(2021) Zhongyan Li et al.   NUCLEIC ACIDS RESEARCH

EP300 Selectively Controls the Enhancer Landscape of MYCN-Amplified Neuroblastoma

(2021) Adam D. Durbin et al.   Cancer Discovery

Drug Discovery Researches on Modulators of Lysine-Modifying Enzymes Based on Strategic Chemistry Approaches

(2020) Yukihiro Itoh   CHEMICAL & PHARMACEUTICAL BULLETIN

Tazemetostat: First Approval

(2020) Sheridan M. Hoy   DRUGS

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

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

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

(2020) Yudao Shen 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

Simultaneous Inhibition of SIRT2 Deacetylase and Defatty-Acylase Activities via a PROTAC Strategy

(2020) Jun Young Hong et al.   ACS Medicinal Chemistry Letters

Induced protein degradation of histone deacetylases 3 (HDAC3) by proteolysis targeting chimera (PROTAC)

(2020) Fangyuan Cao et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Drug design targeting active posttranslational modification protein isoforms

(2020) Fanwang Meng et al.   MEDICINAL RESEARCH REVIEWS

The Functional Deubiquitinating Enzymes in Control of Innate Antiviral Immunity

(2020) Zhi Zong et al.   Advanced Science

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

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

HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells

(2020) Ahlam Ali et al.   Cancers

Developing potent PROTACs tools for selective degradation of HDAC6 protein

(2019) Zixuan An et al.   Protein & Cell

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

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

Polycomb Repressive 2 Complex—Molecular Mechanisms of Function

(2019) Valentina L Kouznetsova et al.   PROTEIN SCIENCE

Development of Multifunctional Histone Deacetylase 6 Degraders with Potent Antimyeloma Activity

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

Lysine acetyltransferases and lysine deacetylases as targets for cardiovascular disease

(2019) Peng Li et al.   Nature Reviews Cardiology

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

Uncoupling of PARP1 trapping and inhibition using selective PARP1 degradation

(2019) Shuai Wang et al.   Nature Chemical Biology

Histone lysine methyltransferases in biology and disease

(2019) Dylan Husmann et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Disordered region of cereblon is required for efficient degradation by proteolysis-targeting chimera

(2019) Kidae Kim et al.   Scientific Reports

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

(2018) Mette Ishoey et al.   ACS Chemical Biology

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

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

Mechanisms of resistance to EZH2 inhibitors in diffuse large B-cell lymphomas

(2018) Malik Bisserier et al.   BLOOD

Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics

(2018) Ibraheem Ali et al.   CHEMICAL REVIEWS

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

Homo-PROTACs for the Chemical Knockdown of Cereblon

(2018) Christian Steinebach et al.   ACS Chemical Biology

The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

(2018) Magnus E. Jakobsson et al.   Nature Communications

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

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

PARP inhibitors: Synthetic lethality in the clinic

(2017) Christopher J. Lord et al.   SCIENCE

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

(2017) Chiara Maniaci et al.   Nature Communications

An Update on Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy

(2016) Ying-Qing Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Histone deacetylase 6 structure and molecular basis of catalysis and inhibition

(2016) Yang Hai et al.   Nature Chemical Biology

Bicyclic-Capped Histone Deacetylase 6 Inhibitors with Improved Activity in a Model of Axonal Charcot–Marie–Tooth Disease

(2015) Sida Shen et al.   ACS Chemical Neuroscience

Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination

(2015) Philip Jones et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2014) Eric S. Fischer et al.   NATURE

INPP4B overexpression enhances the antitumor efficacy of PARP inhibitor AG014699 in MDA-MB-231 triple-negative breast cancer cells

(2014) Ying Sun et al.   TUMOR BIOLOGY

BMN 673, a Novel and Highly Potent PARP1/2 Inhibitor for the Treatment of Human Cancers with DNA Repair Deficiency

(2013) Y. Shen et al.   CLINICAL CANCER RESEARCH

Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs

(2013) J. Hines et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Validation of the multiple sensor mechanism of the Keap1-Nrf2 system

(2012) Kai Takaya et al.   FREE RADICAL BIOLOGY AND MEDICINE

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

(2012) A Lopez-Girona et al.   LEUKEMIA

Chidamide (CS055/HBI-8000): a new histone deacetylase inhibitor of the benzamide class with antitumor activity and the ability to enhance immune cell-mediated tumor cell cytotoxicity

(2011) Zhi-Qiang Ning et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges

(2009) Peter Atadja   CANCER LETTERS

Trim24 targets endogenous p53 for degradation

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

4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: A Novel Bioavailable Inhibitor of Poly(ADP-ribose) Polymerase-1

(2008) Keith A. Menear et al.   JOURNAL OF MEDICINAL CHEMISTRY