4.7 Article

Recent strategies targeting Embryonic Ectoderm Development (EED) for cancer therapy: Allosteric inhibitors, PPI inhibitors, and PROTACs

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Review Chemistry, Medicinal

Targeting PRC2 for the treatment of cancer: an updated patent review (2016-2020)

Milly Dockerill et al.

Summary: PRC2 is a histone methyltransferase complex associated with several cancer types. The recent approval of tazemetostat as the first inhibitor targeting EZH2 marks a milestone in cancer treatment. The exploration of alternative approaches to target PRC2 beyond EZH2 may offer distinct advantages but also pose new challenges in clinical development.

EXPERT OPINION ON THERAPEUTIC PATENTS (2021)

Review Genetics & Heredity

Polycomb Gene Silencing Mechanisms: PRC2 Chromatin Targeting, H3K27me3 'Readout', and Phase Separation-Based Compaction

Yiran Guo et al.

Summary: The modulation of chromatin structure and/or modification by Polycomb repressive complexes (PRCs) plays a crucial role in partitioning the genome and regulating gene activity. PRC2 enzymatic activity and its interaction with cofactors, DNA elements, histones, RNA, and effectors such as canonical PRC1 are intricately regulated to mediate gene silencing through mechanisms like chromatin compaction and histone deacetylation. Understanding the structural architecture and regulation of PRC2, as well as the molecular mechanisms of Polycomb-mediated gene silencing, has significant implications in biology and medicine.

TRENDS IN GENETICS (2021)

Article Chemistry, Medicinal

Diverse, Potent, and Efficacious Inhibitors That Target the EED Subunit of the Polycomb Repressive Complex 2 Methyltransferase

Sharan K. Bagal et al.

Summary: This study identifies potent and orally bioavailable EED ligands with good solubilities, which exhibit in vivo efficacy in EZH2-driven tumors through optimization of design strategies.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Discovery of EEDi-5273 as an Exceptionally Potent and Orally Efficacious EED Inhibitor Capable of Achieving Complete and Persistent Tumor Regression

Rohan Kalyan Rej et al.

Summary: The discovery of exceptionally potent and efficacious EED inhibitors has demonstrated significant potential for the treatment of human cancers and other diseases. Through optimization and structural studies, a promising compound, EEDi-5273, has shown excellent inhibitory effects on tumor growth in experiments.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Pathology

Noncanonical Functions of the Polycomb Group Protein EZH2 in Breast Cancer

Talha Anwar et al.

Summary: EZH2, the catalytic subunit of PRC2, plays a critical role in determining cell identity by depositing trimethyl marks on histone H3. In addition to its well-defined role in transcriptional repression, EZH2 also exerts some histonemethyltransferaseeindependent functions, which are important for breast cancer progression.

AMERICAN JOURNAL OF PATHOLOGY (2021)

Review Oncology

The noncanonical role of EZH2 in cancer

Jinhua Huang et al.

Summary: EZH2, as the catalytic subunit of PRC2, regulates gene expression and plays different roles in various tumor types. Apart from its canonical role in gene silencing, EZH2 also functions as a transcriptional coactivator independently of H3K27me3, critical for cancer progression.

CANCER SCIENCE (2021)

Article Biochemistry & Molecular Biology

Identification of novel EED-EZH2 PPI inhibitors using an in silico fragment mapping method

Kensuke Misawa et al.

Summary: This study aimed to discover novel EED-EZH2 protein-protein interaction (PPI) inhibitors using computational methods. By constructing pharmacophore models and conducting virtual screening, 16 compounds were selected, with five showing inhibitory activities in vitro. This research provides insights into the structural design of new EED-EZH2 PPI inhibitors through in silico fragment mapping.

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN (2021)

Article Chemistry, Medicinal

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

Zhihao Liu et al.

Summary: This study presents a novel strategy for treating cancer by targeting proteasomal degradation to block the oncogenic activity of EZH2, offering a new approach compared to current EZH2 inhibitors.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Review Biochemistry & Molecular Biology

Polycomb-group proteins in the initiation and progression of cancer

Xiujuan Zhao et al.

Summary: Polycomb group proteins are essential chromatin regulators for maintaining cellular identity, and their dysregulation is linked to human cancer. Understanding their role in transcription regulation and DNA damage repair may provide insights for cancer therapy.

JOURNAL OF GENETICS AND GENOMICS (2021)

Review Oncology

Finding an easy way to harmonize: a review of advances in clinical research and combination strategies of EZH2 inhibitors

Chen Li et al.

Summary: EZH2 inhibitors have shown anticancer activity by targeting EZH2, but resistance in some lymphomas and solid tumors calls for combination with other treatment modalities to enhance efficacy. Combining EZH2 inhibitors with therapies such as immunotherapy, chemotherapy, targeted therapy, and endocrine therapy has demonstrated complementary or synergistic antitumor effects.

CLINICAL EPIGENETICS (2021)

Article Chemistry, Medicinal

LYTACs: An Emerging Tool for the Degradation of Non-Cytosolic Proteins

Bhavana Ramadas et al.

Summary: In the last two decades, targeted protein degradation techniques have gained popularity for eliminating disease-causing undruggable proteins. LYTACs are a novel approach that leverages the lysosome degradation pathway to specifically target membrane-bound and extracellular proteins.

CHEMMEDCHEM (2021)

Article Chemistry, Medicinal

Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery

Guoqiang Dong et al.

Summary: Targeted protein degradation through molecular glues is a promising area in drug discovery, offering unique biological activities and physicochemical properties. While classical molecular glue degraders have been serendipitously identified, rational discovery and design strategies are now rapidly emerging.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Structure-Guided Development of Small-Molecule PRC2 Inhibitors Targeting EZH2-EED Interaction

Daohai Du et al.

Summary: DC-PRC2in-01 destabilizes the PRC2 complex, leading to the degradation of PRC2 core proteins and the decrease of global H3K27me3 levels in cancer cells. It effectively inhibits the proliferation of PRC2-driven lymphomas cells and arrests the cell cycle in the G0/G1 phase.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Polycomb Repressive Complex 2 Modulation through the Development of EZH2-EED Interaction Inhibitors and EED Binders

Stefano Tomassi et al.

Summary: Recent research has shown that disrupting the multimeric integrity of the PRC2 complex to cripple its function is a promising approach in cancer treatment. Developing EZH2-EED protein-protein interaction and EED inhibitors as indirect modulators of PRC2-dependent methyltransferase activity has gained significant interest in the scientific community.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Unraveling the Role of Linker Design in Proteolysis Targeting Chimeras

Troy A. Bemis et al.

Summary: A current bottleneck in the development of PROTACs is the empirical nature of linker length structure-activity relationships. A multi-disciplinary approach has been detailed to alleviate this bottleneck. Research has focused on synthetic approaches to increase throughput, advances in structural biology and computational chemistry for rational PROTAC design, and de novo linker design in silico.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Biotechnology & Applied Microbiology

The PROTACtable genome

Melanie Schneider et al.

Summary: This article presents a systematic approach to assessing the PROTAC tractability of protein targets, which could support decision-making on whether a particular target may be amenable to modulation using a PROTAC.

NATURE REVIEWS DRUG DISCOVERY (2021)

Review Biochemistry & Molecular Biology

Going beyond Polycomb: EZH2 functions in prostate cancer

Su H. Park et al.

Summary: EZH2, a core subunit of PRC2, plays a crucial role in regulating cellular identity and stem cell maintenance through its histone methyltransferase activity. Dysregulation of EZH2 is frequently observed in various cancers, including prostate cancer. Despite some studies reporting its tumor suppressive and oncogenic functions, there are discrepancies in EZH2 and H3K27 methylation, and enzymatic inhibitors have shown limited efficacy in prostate cancer.

ONCOGENE (2021)

Review Pharmacology & Pharmacy

Naturally occurring coumestans from plants, their biological activities and therapeutic effects on human diseases

Yanbei Tu et al.

Summary: This comprehensive review summarizes the chemical structures and diverse pharmacological activities of coumestans isolated from various plant sources, providing important information on their medicinal values and potential for the rational design and development of more effective drugs. The focus on the counteraction of coumestans against bone diseases and organ damages, along with the involved molecular mechanisms, offers insights into the therapeutic potential of these compounds.

PHARMACOLOGICAL RESEARCH (2021)

Review Cell Biology

Opportunities and Challenges of Small Molecule Induced Targeted Protein Degradation

Ming He et al.

Summary: PROTAC is a new technology for inducing protein degradation using small molecules, which shows advantages in overcoming tumor resistance, affecting non-enzymatic functions of target proteins, degrading undruggable targets, and providing rapid and reversible chemical knockout tools. However, it also faces challenges and issues as a rapidly developing new chemical biology technology.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Article Medicine, Research & Experimental

Pharmacological inhibition of noncanonical EED-EZH2 signaling overcomes chemoresistance in prostate cancer

Xin Li et al.

Summary: The study identified LG1980 as a lead compound that effectively suppresses the growth of chemoresistant prostate cancer cells and synergistically enhances the efficacy of docetaxel in animal models, highlighting its potential as a novel strategy for the treatment of chemoresistant prostate cancer.

THERANOSTICS (2021)

Review Oncology

Engaging chromatin: PRC2 structure meets function

Paul Chammas et al.

BRITISH JOURNAL OF CANCER (2020)

Review Biochemistry & Molecular Biology

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery

George M. Burslem et al.

Article Biochemistry & Molecular Biology

Discovery of a first-in-class EZH2 selective degrader

Anqi Ma et al.

NATURE CHEMICAL BIOLOGY (2020)

Review Chemistry, Multidisciplinary

Prey for the Proteasome: Targeted Protein Degradation-A Medicinal Chemist's Perspective

Laura M. Luh et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2020)

Article Pharmacology & Pharmacy

Tazemetostat: First Approval

Sheridan M. Hoy

Review Oncology

EZH2: a novel target for cancer treatment

Ran Duan et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

Review Oncology

EZH2-Targeted Therapies in Cancer: Hype or a Reality

Marie-Lisa Eich et al.

CANCER RESEARCH (2020)

Article Multidisciplinary Sciences

Lysosome-targeting chimaeras for degradation of extracellular proteins

Steven M. Banik et al.

NATURE (2020)

Review Chemistry, Medicinal

PROTAC: A promising technology for cancer treatment

Xin Zhou et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2020)

Article Chemistry, Medicinal

Small Molecule Approaches for Targeting the Polycomb Repressive Complex 2 (PRC2) in Cancer

M. Cynthia Martin et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Article Biochemistry & Molecular Biology

EED-Targeted PROTACs Degrade EED, EZH2, and SUZ12 in the PRC2 Complex

Jessie Hao-Ru Hsu et al.

CELL CHEMICAL BIOLOGY (2020)

Article Biochemistry & Molecular Biology

Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader

Frances Potjewyd et al.

CELL CHEMICAL BIOLOGY (2020)

Review Pharmacology & Pharmacy

Polycomb repressive complex 2 inhibitors: emerging epigenetic modulators

Danishuddin et al.

DRUG DISCOVERY TODAY (2019)

Article Biochemistry & Molecular Biology

EZH2 cooperates with gain-of-function p53 mutants to promote cancer growth and metastasis

Yu Zhao et al.

EMBO JOURNAL (2019)

Review Cell Biology

PRC2 is high maintenance

Jia-Ray Yu et al.

GENES & DEVELOPMENT (2019)

Review Biochemistry & Molecular Biology

Molecular Mechanisms Directing PRC2 Recruitment and H3K27 Methylation

Anne Laugesen et al.

MOLECULAR CELL (2019)

Review Biochemistry & Molecular Biology

Polycomb repressive 2 complex-Molecular mechanisms of function

Valentina L. Kouznetsova et al.

PROTEIN SCIENCE (2019)

Review Biochemistry & Molecular Biology

Emerging Roles for Polycomb-Group Proteins in Stem Cells and Cancer

Ho Lam Chan et al.

TRENDS IN BIOCHEMICAL SCIENCES (2019)

Article Chemistry, Multidisciplinary

AZD9291 inactivates the PRC2 complex to mediate tumor growth inhibition

Kai-li Zhang et al.

ACTA PHARMACOLOGICA SINICA (2019)

Article Biochemistry & Molecular Biology

EZH2 upregulates the PI3K/AKT pathway through IGF1R and MYC in clinically aggressive chronic lymphocytic leukaemia

Subazini Thankaswamy Kosalai et al.

EPIGENETICS (2019)

Review Pharmacology & Pharmacy

Targeting epigenetic machinery: Emerging novel allosteric inhibitors

Fei Ye et al.

PHARMACOLOGY & THERAPEUTICS (2019)

Article Multidisciplinary Sciences

PRC2 engages a bivalent H3K27M-H3K27me3 dinucleosome inhibitor

Katharine L. Diehl et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Article Biochemistry & Molecular Biology

AUTACs: Cargo-Specific Degraders Using Selective Autophagy

Daiki Takahashi et al.

MOLECULAR CELL (2019)

Review Biochemistry & Molecular Biology

PROTACs: great opportunities for academia and industry

Xiuyun Sun et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2019)

Review Biochemistry & Molecular Biology

Structure, mechanism, and regulation of polycomb-repressive complex 2

Lindsay E. Moritz et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

Review Oncology

Histone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer

Bayley A. Jones et al.

MOLECULAR CANCER THERAPEUTICS (2018)

Article Biochemistry & Molecular Biology

Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding

Siming Chen et al.

MOLECULAR CELL (2018)

Article Biochemistry & Molecular Biology

Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin

Chul-Hwan Lee et al.

MOLECULAR CELL (2018)

Article Biochemistry & Molecular Biology

Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes

Simon Poepsel et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2018)

Article Multidisciplinary Sciences

Structures of human PRC2 with its cofactors AEBP2 and JARID2

Vignesh Kasinath et al.

SCIENCE (2018)

Article Biochemistry & Molecular Biology

Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes

Simon Poepsel et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2018)

Review Biochemistry & Molecular Biology

WD40 Repeat Proteins: Signalling Scaffold with Diverse Functions

Buddhi Prakash Jain et al.

PROTEIN JOURNAL (2018)

Article Chemistry, Multidisciplinary

Six Years (2012-2018) of Researches on Catalytic EZH2 Inhibitors: The Boom of the 2-Pyridone Compounds

Rossella Fioravanti et al.

CHEMICAL RECORD (2018)

Article Chemistry, Multidisciplinary

Development of a high-throughput fluorescence polarization assay for the discovery of EZH2-EED interaction inhibitors

Mao-rong Zhu et al.

ACTA PHARMACOLOGICA SINICA (2018)

Review Chemistry, Multidisciplinary

Inhibitors of Protein Methyltransferases and Demethylases

H. Umit Kaniskan et al.

CHEMICAL REVIEWS (2018)

Article Biochemistry & Molecular Biology

Polycomb repressive complex 2 in an autoinhibited state

Matthew Bratkowski et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2017)

Review Biochemistry & Molecular Biology

The Multiple Facets of PRC2 Alterations in Cancers

M. Wassef et al.

JOURNAL OF MOLECULAR BIOLOGY (2017)

Article Biochemistry & Molecular Biology

An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED

Wei Qi et al.

NATURE CHEMICAL BIOLOGY (2017)

Article Biochemistry & Molecular Biology

Structural basis of PROTAC cooperative recognition for selective protein degradation

Morgan S. Gadd et al.

NATURE CHEMICAL BIOLOGY (2017)

Article Biochemistry & Molecular Biology

The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex

Yupeng He et al.

NATURE CHEMICAL BIOLOGY (2017)

Article Chemistry, Applied

Discovery of Peptidomimetic Ligands of EED as Allosteric Inhibitors of PRC2

Kimberly D. Barnash et al.

ACS COMBINATORIAL SCIENCE (2017)

Review Chemistry, Multidisciplinary

Small-Molecule Modulation of Protein Homeostasis

George M. Burslem et al.

CHEMICAL REVIEWS (2017)

Review Chemistry, Multidisciplinary

Structure of the PRC2 complex and application to drug discovery

Yi Shi et al.

ACTA PHARMACOLOGICA SINICA (2017)

Article Chemistry, Medicinal

SAR of amino pyrrolidines as potent and novel protein-protein interaction inhibitors of the PRC2 complex through EED binding

Michael L. Curtin et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2017)

Article Multidisciplinary Sciences

Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2

Neil Justin et al.

NATURE COMMUNICATIONS (2016)

Article Biochemistry & Molecular Biology

Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation

Serena Sanulli et al.

MOLECULAR CELL (2015)

Article Biochemistry & Molecular Biology

SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2

Kimberly H. Kim et al.

NATURE MEDICINE (2015)

Article Biochemistry & Molecular Biology

Elements of the Polycomb Repressor SU(Z) 12 Needed for Histone H3-K27 Methylation, the Interface with E(Z), and In Vivo Function

Aswathy N. Rai et al.

MOLECULAR AND CELLULAR BIOLOGY (2013)

Article Biochemistry & Molecular Biology

PAF and EZH2 Induce Wnt/β-Catenin Signaling Hyperactivation

Hae-Yun Jung et al.

MOLECULAR CELL (2013)

Article Biochemistry & Molecular Biology

Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer

Woojin Kim et al.

NATURE CHEMICAL BIOLOGY (2013)

Article Cell Biology

PRC2 directly methylates GATA4 and represses its transcriptional activity

Aibin He et al.

GENES & DEVELOPMENT (2012)

Article Multidisciplinary Sciences

Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27)

Michael T. McCabe et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

Article Biochemistry & Molecular Biology

Context-Specific Regulation of NF-κB Target Gene Expression by EZH2 in Breast Cancers

Shuet Theng Lee et al.

MOLECULAR CELL (2011)

Article Multidisciplinary Sciences

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Ryan D. Morin et al.

NATURE (2011)

Review Multidisciplinary Sciences

The Polycomb complex PRC2 and its mark in life

Raphael Margueron et al.

NATURE (2011)

Article Biochemistry & Molecular Biology

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

Taavi K. Neklesa et al.

NATURE CHEMICAL BIOLOGY (2011)

Article Cell Biology

Polycomb complexes act redundantly to repress genomic repeats and genes

Martin Leeb et al.

GENES & DEVELOPMENT (2010)

Article Multidisciplinary Sciences

Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2)

Chao Xu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Review Cell Biology

Biochemical mechanisms of gene regulation by polycomb group protein complexes

Juerg Mueller et al.

CURRENT OPINION IN GENETICS & DEVELOPMENT (2009)

Article Multidisciplinary Sciences

Role of the polycomb protein EED in the propagation of repressive histone marks

Raphael Margueron et al.

NATURE (2009)

Article Oncology

Green Tea Extracts for the Prevention of Metachronous Colorectal Adenomas: A Pilot Study

Masahito Shimizu et al.

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION (2008)

Article Biochemistry & Molecular Biology

Structural basis of EZH2 recognition by EED

Zhifu Han et al.

STRUCTURE (2007)

Article Biochemistry & Molecular Biology

Integration of estrogen and Wnt signaling circuits by the polycomb group protein EZH2 in breast cancer cells

Bin Shi et al.

MOLECULAR AND CELLULAR BIOLOGY (2007)