☆ 4.8 Review

PROTAC degraders as chemical probes for studying target biology and target validation

CHEMICAL SOCIETY REVIEWS (2022)

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。

Article Chemistry, Multidisciplinary

Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications

Nathaniel J. Henning et al.

Summary: This study describes a covalent ligand EN106 that targets FEM IB, an E3 ligase involved in the cellular response to reductive stress. EN106 disrupts the recognition of the reductive stress substrate FNIP1 by targeting C186 in FEM1B. Additionally, EN106 can serve as a covalent recruiter for FEM1B in targeted protein degradation (TPD) applications, leading to the degradation of BRD4 and BCR-ABL when linked to BET bromodomain inhibitor JQ1 or kinase inhibitor dasatinib, respectively.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Image-Based Annotation of Chemogenomic Libraries for Phenotypic Screening

Amelie Tjaden et al.

Summary: Phenotypical screening is a common method in drug discovery, but functional annotation of identified hits is often challenging. This study presents an optimized live-cell multiplexed assay for comprehensive time-dependent characterization of the effect of small molecules on cellular health.

MOLECULES (2022)

添加到收藏夹

Review Biochemistry & Molecular Biology

Small molecule targeting of chromatin writers in cancer

Andrew R. Conery et al.

Summary: The approval of the first histone methyltransferase inhibitor in 2020 marks a significant milestone in the field of targeted manipulation of chromatin regulatory pathways for cancer treatment. Despite the complexity of identifying key targets for therapeutic intervention, approaches in chemical biology have played a critical role in discovering key nodes in these pathways and translating them into potential cancer therapies. This review highlights the importance of chemical probes, drug candidates, and translational strategies in maximizing the impact of epigenetic writer enzymes in cancer therapy.

NATURE CHEMICAL BIOLOGY (2022)

添加到收藏夹

Review Biochemistry & Molecular Biology

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

Zhenyi Hu et al.

Summary: PROTACs are an emerging technology that utilizes the ubiquitin-proteasome system for targeted protein degradation, showing great therapeutic potential in treating diseases. Over the past two decades, significant advancements have been made in PROTAC technology, with an increasing repertoire of targets.

CHEMBIOCHEM (2022)

添加到收藏夹

Review Chemistry, Medicinal

Targeting epigenetic modulators using PROTAC degraders: Current status and future perspective

Thomas Webb et al.

Summary: Epigenetic modulators play a crucial role in gene expression and their dysregulation is associated with disease pathogenesis. Small molecule inhibitors targeting epigenetic proteins have limitations, but protein degraders can better exploit target druggability.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2022)

添加到收藏夹

Review Biochemistry & Molecular Biology

BET bromodomain inhibitors

Martin P. Schwalm et al.

Summary: Lysine acetylation creates docking sites for epigenetic reader domains of BET bromodomain proteins, which are important regulators of linage specific gene transcription. The development of potent and selective inhibitors has facilitated mechanistic studies in disease models and translation into clinical practice. Advances in pan-BET inhibitors have led to second generation inhibitors with improved selectivity, as well as highly potent bifunctional and dual inhibitors, expanding the toolbox for research on acetylation dependent transcription, BET-associated diseases, and epigenetic reader domains.

CURRENT OPINION IN CHEMICAL BIOLOGY (2022)

添加到收藏夹

Article Chemistry, Medicinal

The Ascension of Targeted Covalent Inhibitors

Juswinder Singh

Summary: Covalent drugs have had a significant impact on human health, but they were previously avoided by the pharmaceutical industry due to concerns about potential toxicity. However, there has been a resurgence in interest with the clinical success of targeted covalent inhibitors (TCIs) and the approval of eight drugs in the past decade. The ability to create unique drugs through the covalent mechanism of action has led to clinically decisive target product profiles. TCIs have revolutionized the treatment approach for non-small-cell lung cancer and chronic lymphocytic leukemia. This Perspective article highlights the clinical and financial success of this drug class and provides early insights into toxicity, a previously hindering factor in the field.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Chemistry, Multidisciplinary

Fluorescent and Bioluminescent Calcium Indicators with Tuneable Colors and Affinities

Nicole Mertes et al.

Summary: We introduce a family of bright, rhodamine-based calcium indicators with tuneable affinities and colors. The indicators can be specifically localized to different cellular compartments and are compatible with both fluorescence and bioluminescence readouts through conjugation to HaloTag fusion proteins. Their increase in fluorescence upon localization enables no-wash live-cell imaging, facilitating their use in biological assays. These indicators are versatile and easy to use, making them powerful tools for bioimaging and bioassays.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti-cancer therapeutic

Dongxu Li et al.

Summary: A new proteolysis targeting chimera (PROTAC) named MS40 has been developed to selectively degrade WDR5 and Ikaros, showing promising anti-cancer effects in MLL-rearranged leukemias.

ONCOGENE (2022)

添加到收藏夹

Article Cell Biology

A Toolbox for the Generation of Chemical Probes for Baculovirus IAP Repeat Containing Proteins

Martin P. Schwalm et al.

Summary: E3 ligases play a crucial role in regulating protein homeostasis by recruiting substrate proteins to the proteasomal degradation machinery. Recent research has focused on the Baculovirus IAP Repeat (BIR) family of E3 ligases, which contain a structurally conserved but diverse protein interaction domain. The Inhibitors of Apoptosis (IAP) family, which typically have three BIR domains, are promising drug targets. However, there is currently a lack of assay tools to evaluate the selectivity of inhibitors in this target area.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Target 2035-update on the quest for a probe for every protein

Susanne Mueller et al.

Summary: Twenty years after the first draft of the human genome was published, our understanding of the human proteome is still incomplete. The majority of proteins in the human proteome remain uncharacterized, with only a small percentage successfully targeted for drug discovery. Target 2035 aims to bridge this gap by developing new technologies for the entire human proteome by 2035.

RSC MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Biology

Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool

Richard Wang et al.

Summary: In this study, a PROTAC derivative of AURKA inhibitor MLN8237 was characterized for its efficient and specific destruction of AURKA. The subcellular localization and differential sensitivity of AURKA pools to PROTAC action were demonstrated, highlighting the potential of this new class of degrader compounds for targeting specific subpopulations within cells. The findings suggest that PROTACs can modulate AURKA functions in distinct cellular compartments, providing a novel approach for therapeutic intervention.

COMMUNICATIONS BIOLOGY (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

PROTAC-DB: an online database of PROTACs

Gaoqi Weng et al.

Summary: PROTACs, a novel therapeutic technology that selectively degrades targeted proteins, has achieved significant progress with two PROTACs in phase I clinical trials. However, the design of PROTACs remains challenging. PROTAC-DB, a web-based database, integrates structural information and experimental data of PROTACs, providing convenient querying and filtering tools for researchers.

NUCLEIC ACIDS RESEARCH (2021)

添加到收藏夹

Article Chemistry, Medicinal

Solution Conformations Shed Light on PROTAC Cell Permeability

Yoseph Atilaw et al.

Summary: PROTACs induce intracellular degradation of target proteins through a bifunctional structure. Structural insights into a VHL-based PROTAC revealed elongated and polar conformations in solutions, suggesting the importance of molecular chameleonicity for cell permeability.

ACS MEDICINAL CHEMISTRY LETTERS (2021)

添加到收藏夹

Article Chemistry, Medicinal

Development of BromoTag: A Bump-and-Hole-PROTAC System to Induce Potent, Rapid, and Selective Degradation of Tagged Target Proteins

Adam G. Bond et al.

Summary: This study describes the design and development of a new protein degradation system utilizing a variant of the Brd4 bromodomain as a degradation tag. The system effectively degrades BromoTagged proteins in a fast, selective manner, showing favorable pharmacokinetic profile in mice. This system expands the arsenal of chemical genetic degradation tools for manipulating protein levels and exploring therapeutic potential in cells and in vivo.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of a Highly Potent and Selective Degrader Targeting Hematopoietic Prostaglandin D Synthase via In Silico Design

Hidetomo Yokoo et al.

Summary: PROTAC, an important modality for targeted protein degradation, requires careful selection of appropriate linker, E3 ligase ligand, and target protein ligand for successful development. In silico simulation can be a useful tool for rational development of PROTACs.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Amide-to-Ester Substitution as a Strategy for Optimizing PROTAC Permeability and Cellular Activity

Victoria G. Klein et al.

Summary: The study explores the potential of enhancing PROTAC permeability and bioactivity by replacing amides with esters, leading to the design of novel VHL-based BET degraders. Ester PROTACs exhibited improved cell permeability and more potent protein degradation effects.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Cell Biology

A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models

Xufen Yu et al.

Summary: This study proposes pharmacological degradation of WDR5 as a promising therapeutic strategy for treating WDR5-dependent tumors and presents two high-resolution crystal structures of WDR5-degrader-E3 ligase ternary complexes. The designed WDR5 degrader, MS67, potently and selectively depleted WDR5, demonstrating higher efficacy than WDR5 PPI inhibitors in suppressing transcription of WDR5-regulated genes and inhibiting cancer cell proliferation. These findings suggest structure-based design can effectively identify highly active degraders for potential treatment of WDR5-dependent cancers.

SCIENCE TRANSLATIONAL MEDICINE (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

The Promise and Peril of Chemical Probe Negative Controls

Jinyoung Lee et al.

Summary: The study compared the selectivity profiles of four chemical probes and their respective negative controls, finding that chemical modifications neutralizing the charge can result in up to 80% of known off-targets being inactive against the control. Careful selection of negative controls for chemical probes is emphasized, and it is best practice to verify that two unrelated chemical probes targeting the same protein elicit the same phenotype.

ACS CHEMICAL BIOLOGY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Design, Synthesis, and Evaluation of WD-Repeat-Containing Protein 5 (WDR5) Degraders

Anja Doelle et al.

Summary: H3K4 methylation is a hallmark of actively transcribed genes, with WDR5 associated with noncoding RNAs and MYC. WDR5 has been identified as a potential drug target, and the design of WDR5 degraders and the nature of the linker play a key role in degradation efficacy.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Chemistry, Multidisciplinary

DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras

Xiaoyu Zhang et al.

Summary: Ligand-induced protein degradation through electrophilic PROTACs has been shown to degrade proteins in human cells by engaging specific cysteines in the poorly characterized E3 ligase substrate adaptor DCAF11. These findings suggest DCAF11 as a potential E3 ligase for ligand-induced protein degradation via electrophilic PROTACs, providing new insights for the development of targeted protein degradation compounds.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

添加到收藏夹

Review Chemistry, Multidisciplinary

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

Carlotta Cecchini et al.

Summary: PROTACs are heterobifunctional degraders that eliminate targeted proteins by utilizing the UPS system, showing potential as an appealing technology in drug discovery. However, their poor cellular permeability due to high molecular weight and large polar surface area poses challenges, requiring strategies and biological tools to enhance cellular uptake.

FRONTIERS IN CHEMISTRY (2021)

添加到收藏夹

Article Biochemical Research Methods

A Method for Determining the Kinetics of Small-Molecule-Induced Ubiquitination

Ellen F. Vieux et al.

Summary: This work developed an in vitro system to measure the kinetics of BRD4 BD1 ubiquitination and characterized the affinities between BiDACs, BD1, and CRBN, providing a new tool for understanding and optimizing the catalytic and thermodynamic properties of BiDACs.

SLAS DISCOVERY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Prediction of Chameleonic Efficiency

Laurent David et al.

Summary: This study introduces the application of chameleonic properties in drug molecules, establishing models for predicting drug polarity and hydrogen bond donor characteristics through experimental measurement models and molecular dynamics simulations. These methods can be useful for triaging designed molecules and prioritizing those with the best chance of achieving acceptable permeability and solubility.

CHEMMEDCHEM (2021)

添加到收藏夹

Article Chemistry, Medicinal

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

Mengzhu Zheng et al.

Summary: Inspired by the success of dual-targeting drugs, the study combines the concept of PROTAC and dual targeting to design and synthesize dual PROTAC molecules, which can degrade two different targets simultaneously. Novel dual-targeting PROTAC molecules have been successfully prepared and demonstrated to degrade both EGFR and PARP in cancer cells, expanding the application of PROTAC method in drug discovery.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Review Biotechnology & Applied Microbiology

Trends in kinase drug discovery: targets, indications and inhibitor design

Misty M. Attwood et al.

Summary: The article analyzes the landscape of approved and investigational therapies that target kinases, highlighting the increasing importance of kinase inhibitors in oncology and beyond. It discusses trends in kinase inhibitor design and points out that there are still substantial unexplored opportunities for this drug class.

NATURE REVIEWS DRUG DISCOVERY (2021)

添加到收藏夹

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)

添加到收藏夹

Article Biochemical Research Methods

Engineering Single Pan-Specific Ubiquibodies for Targeted Degradation of All Forms of Endogenous ERK Protein Kinase

Erin A. Stephens et al.

Summary: Ubiquibodies are a customizable proteome editing technology that uses E3 ubiquitin ligases fused to synthetic binding proteins to degrade proteins of interest at the proteasome. Engineered uAbs can accelerate protein turnover, aiding in the study of cellular protein properties.

ACS SYNTHETIC BIOLOGY (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Chemo-proteomics exploration of HDAC degradability by small molecule degraders

Yuan Xiong et al.

Summary: The study synthesized a pan-HDAC degrader library for exploring acute degradation of chromatin-modifying enzymes, identifying leads for targeting HDACs 1-8 and 10. Cell line-driven target specificity and collateral loss of HDAC-containing repressive complexes were discovered upon HDAC degradation, potentially offering a new mechanism for controlling chromatin structure.

CELL CHEMICAL BIOLOGY (2021)

添加到收藏夹

Review Biochemistry & Molecular Biology

Targeted protein degradation: A promise for undruggable proteins

Kusal T. G. Samarasinghe et al.

Summary: Protein homeostasis is crucial for maintaining a balanced, healthy environment within cells, but excessive dysregulated proteins can lead to disease. PROTACs and other Targeted Protein Degradation (TPD) strategies are emerging as potential therapeutic modalities for degrading disease-causing proteins, including previously undruggable targets like transcription factors.

CELL CHEMICAL BIOLOGY (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2

Benedict-Tilman Berger et al.

Summary: A structure-based rationale for kinetic selectivity between FAK and PYK2 kinases was reported, showing that slowly dissociating FAK inhibitors induce helical structure at the DFG motif of FAK but not PYK2. The role of hydrophobic interactions and protein structural mobility in regulating the kinetic selectivity of inhibitors was highlighted, providing insights for rational optimization of ligand residence times.

CELL CHEMICAL BIOLOGY (2021)

添加到收藏夹

Review Immunology

Genomics-driven drug discovery based on disease-susceptibility genes

Kyuto Sonehara et al.

Summary: Genome-wide association studies have revealed numerous disease-susceptibility genes, highlighting the importance of translating this knowledge into clinical practice. However, the challenges of finding effective drug targets and estimating potential side effects often lead to failures in promising clinical trials. Recent advances in genetics-led drug discovery, including drug repurposing, Mendelian randomization, and the use of multifaceted omics data, offer potential solutions to overcome these challenges.

INFLAMMATION AND REGENERATION (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product function

Mai Luo et al.

Summary: This study found that the natural product nimbolide can be used as a recruiter of the E3 ubiquitin ligase RNF114 for targeted protein degradation, which is important in modern drug discovery. Through activity-based protein profiling-enabled ligand screening, fully synthetic molecules mimicking nimbolide were discovered, showing potential for degrading therapeutic targets.

CELL CHEMICAL BIOLOGY (2021)

添加到收藏夹

Article Chemistry, Multidisciplinary

Structure-Based Design of a Macrocyclic PROTAC

Andrea Testa et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2020)

添加到收藏夹

Review Pharmacology & Pharmacy

Critical Assessment of Targeted Protein Degradation as a Research Tool and Pharmacological Modality

Milka Kostic et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2020)

添加到收藏夹

Article Chemistry, Multidisciplinary

Efficient Targeted Degradation via Reversible and Irreversible Covalent PROTACs

Ronen Gabizon et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2020)

添加到收藏夹

Article Chemistry, Multidisciplinary

Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs

Michael J. Bond et al.

ACS CENTRAL SCIENCE (2020)

添加到收藏夹

Article Chemistry, Medicinal

Understanding and Improving the Membrane Permeability of VH032-Based PROTACs

Victoria G. Klein et al.

ACS MEDICINAL CHEMISTRY LETTERS (2020)

添加到收藏夹

Article Chemistry, Medicinal

PRosettaC: Rosetta Based Modeling of PROTAC Mediated Ternary Complexes

Daniel Zaidman et al.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2020)

添加到收藏夹

Article Biochemistry & Molecular Biology

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

Bikash Adhikari et al.

NATURE CHEMICAL BIOLOGY (2020)

添加到收藏夹

Article Multidisciplinary Sciences

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

Wen-Hao Guo et al.

NATURE COMMUNICATIONS (2020)

添加到收藏夹

Article Multidisciplinary Sciences

Bardoxolone conjugation enables targeted protein degradation of BRD4

Bingqi Tong et al.

SCIENTIFIC REPORTS (2020)

添加到收藏夹

Review Genetics & Heredity

Advances in Genomics for Drug Development

Roberto Spreafico et al.

GENES (2020)

添加到收藏夹

Article Chemistry, Medicinal

Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis

Marek Wanior et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

添加到收藏夹

Article Biology

Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2

Alina Mares et al.

COMMUNICATIONS BIOLOGY (2020)

添加到收藏夹

Article Biochemistry & Molecular Biology

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

Carl C. Ward et al.

ACS CHEMICAL BIOLOGY (2019)

添加到收藏夹

Article Multidisciplinary Sciences

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

Stefanie Lindner et al.

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS (2019)

添加到收藏夹

Review Chemistry, Medicinal

Proteolysis targeting chimeras (PROTACs) in 'beyond rule-of-five' chemical space: Recent progress and future challenges

Scott D. Edmondson et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2019)

添加到收藏夹

Article Oncology

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

George M. Burslem et al.

CANCER RESEARCH (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

William Farnaby et al.

NATURE CHEMICAL BIOLOGY (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16

Xiaoyu Zhang et al.

NATURE CHEMICAL BIOLOGY (2019)

添加到收藏夹

Review Pharmacology & Pharmacy

PROTACs- a game-changing technology

Markella Konstantinidou et al.

EXPERT OPINION ON DRUG DISCOVERY (2019)

添加到收藏夹

Article Chemistry, Medicinal

Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders

Shang Su et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

添加到收藏夹

Review Physiology

Enzymatic Logic of Ubiquitin Chain Assembly

Kirandeep K. Deol et al.

FRONTIERS IN PHYSIOLOGY (2019)

添加到收藏夹

Article Chemistry, Medicinal

Public resources for chemical probes: the journey so far and the road ahead

Albert A Antolin et al.

Future Medicinal Chemistry (2019)

添加到收藏夹

Article Chemistry, Analytical

Linker length affects photostability of protein-targeted sensor of cellular microviscosity

Marketa Kubankova et al.

METHODS AND APPLICATIONS IN FLUORESCENCE (2019)

添加到收藏夹

Article Chemistry, Medicinal

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

Vittoria Zoppi et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

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

Sajid Khan et al.

NATURE MEDICINE (2019)

添加到收藏夹

Article Multidisciplinary Sciences

Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase

Blake E. Smith et al.

NATURE COMMUNICATIONS (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

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

Christopher P. Tinworth et al.

ACS CHEMICAL BIOLOGY (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

SPR-Measured Dissociation Kinetics of PROTAC Ternary Complexes Influence Target Degradation Rate

Michael J. Roy et al.

ACS CHEMICAL BIOLOGY (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML

Matthias Brand et al.

CELL CHEMICAL BIOLOGY (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation

Calla M. Olson et al.

NATURE CHEMICAL BIOLOGY (2018)

添加到收藏夹

Review Chemistry, Multidisciplinary

The Cysteinome of Protein Kinases as a Target in Drug Development

Apirat Chaikuad et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2018)

添加到收藏夹

Review Medicine, General & Internal

Genomic insights into the causes of type 2 diabetes

Claudia Langenberg et al.

LANCET (2018)

添加到收藏夹

Article Oncology

Protein targeting chimeric molecules specific for bromodomain and extra-terminal motif family proteins are active against pre-clinical models of multiple myeloma

Xiaohui Zhang et al.

LEUKEMIA (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

Plasticity in binding confers selectivity in ligand-induced protein degradation

Radoslaw P. Nowak et al.

NATURE CHEMICAL BIOLOGY (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

Lara N. Gechijian et al.

NATURE CHEMICAL BIOLOGY (2018)

添加到收藏夹

Article Multidisciplinary Sciences

Targetable BET proteins- and E2F1-dependent transcriptional program maintains the malignancy of glioblastoma

Liang Xu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

添加到收藏夹

Article Chemistry, Medicinal

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

John M. Hatcher et al.

ACS MEDICINAL CHEMISTRY LETTERS (2018)

添加到收藏夹

Article Biology

Donated chemical probes for open science

Susanne Mueller et al.

ELIFE (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

Modulating PCAF/GCN5 Immune Cell Function through a PROTAC Approach

Zuni I. Bassi et al.

ACS CHEMICAL BIOLOGY (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

Quantitative Live-Cell Kinetic Degradation and Mechanistic Profiling of PROTAC Mode of Action

Kristin M. Riching et al.

ACS CHEMICAL BIOLOGY (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

CRISPR-Mediated Tagging of Endogenous Proteins with a Luminescent Peptide

Marie K. Schwinn et al.

ACS CHEMICAL BIOLOGY (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader

Hai-Tsang Huang et al.

CELL CHEMICAL BIOLOGY (2018)

添加到收藏夹

Article Biochemistry & Molecular Biology

Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead

Daniel P. Bondeson et al.

CELL CHEMICAL BIOLOGY (2018)

添加到收藏夹

Review Biochemistry & Molecular Biology

Chemical probes targeting epigenetic proteins: Applications beyond oncology

Suzanne Ackloo et al.

EPIGENETICS (2017)

添加到收藏夹

Article Biochemistry & Molecular Biology

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

Georg E. Winter et al.

MOLECULAR CELL (2017)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structural basis of PROTAC cooperative recognition for selective protein degradation

Morgan S. Gadd et al.

NATURE CHEMICAL BIOLOGY (2017)

添加到收藏夹

Review Biotechnology & Applied Microbiology

WD40 repeat domain proteins: a novel target class?

Matthieu Schapira et al.

NATURE REVIEWS DRUG DISCOVERY (2017)

添加到收藏夹

Article Genetics & Heredity

Assessing histone demethylase inhibitors in cells: lessons learned

Stephanie B. Hatch et al.

EPIGENETICS & CHROMATIN (2017)

添加到收藏夹

Article Oncology

Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology

Julian Blagg et al.

CANCER CELL (2017)

添加到收藏夹

Article Chemistry, Multidisciplinary

Degradation of the BAF Complex Factor BRD9 by Heterobifunctional Ligands

David Remillard et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2017)

添加到收藏夹

Review Biochemistry & Molecular Biology

Chemical approaches to targeted protein degradation through modulation of the ubiquitin-proteasome pathway

Ian Collins et al.

BIOCHEMICAL JOURNAL (2017)

添加到收藏夹

Review Oncology

A chemical probe toolbox for dissecting the cancer epigenome

Jake Shortt et al.

NATURE REVIEWS CANCER (2017)

添加到收藏夹

Review Chemistry, Multidisciplinary

Small-Molecule PROTACS: New Approaches to Protein Degradation

Momar Toure et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2016)

添加到收藏夹

Article Chemistry, Medicinal

Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1)

Matthaeus Getlik et al.

JOURNAL OF MEDICINAL CHEMISTRY (2016)

添加到收藏夹

Article Biochemistry & Molecular Biology

Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket

Michael Forster et al.

CELL CHEMICAL BIOLOGY (2016)

添加到收藏夹

Article Biochemistry & Molecular Biology

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

Michael Zengerle et al.

ACS CHEMICAL BIOLOGY (2015)

添加到收藏夹

Article Oncology

The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNFMutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies

Bhavatarini Vangamudi et al.

CANCER RESEARCH (2015)

添加到收藏夹

Article Biochemistry & Molecular Biology

Mapping Proteome-Wide Targets of Environmental Chemicals Using Reactivity-Based Chemoproteomic Platforms

Daniel Medina-Cleghorn et al.

CHEMISTRY & BIOLOGY (2015)

添加到收藏夹

Review Chemistry, Medicinal

Open access chemical probes for epigenetic targets

Peter J. Brown et al.

FUTURE MEDICINAL CHEMISTRY (2015)

添加到收藏夹

Article Biochemistry & Molecular Biology

The ins and outs of selective kinase inhibitor development

Susanne Mueller et al.

NATURE CHEMICAL BIOLOGY (2015)

添加到收藏夹

Article Biochemistry & Molecular Biology

The promise and peril of chemical probes

Cheryl H. Arrowsmith et al.

NATURE CHEMICAL BIOLOGY (2015)

添加到收藏夹

Article Multidisciplinary Sciences

Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance

Oleg Fedorov et al.

SCIENCE ADVANCES (2015)

添加到收藏夹

Article Chemistry, Multidisciplinary

Improving on Nature: Making a Cyclic Heptapeptide Orally Bioavailable

Daniel S. Nielsen et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2014)

添加到收藏夹

Review Biochemistry & Molecular Biology

RING-type E3 ligases: Master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination

Meredith B. Metzger et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2014)

添加到收藏夹

Article Biochemistry & Molecular Biology

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

Pietro Ciceri et al.

NATURE CHEMICAL BIOLOGY (2014)

添加到收藏夹

Review Biotechnology & Applied Microbiology

Targeting bromodomains: epigenetic readers of lysine acetylation

Panagis Filippakopoulos et al.

NATURE REVIEWS DRUG DISCOVERY (2014)

添加到收藏夹

Review Oncology

Aurora-A: a potential DNA repair modulator

Yan Wang et al.

TUMOR BIOLOGY (2014)

添加到收藏夹

Article Multidisciplinary Sciences

UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids

Dawn M. Wenzel et al.

NATURE (2011)

添加到收藏夹

Editorial Material Biochemistry & Molecular Biology

Probing the Probes: Fitness Factors For Small Molecule Tools

Paul Workman et al.

CHEMISTRY & BIOLOGY (2010)

添加到收藏夹

Article Multidisciplinary Sciences

Selective inhibition of BET bromodomains

Panagis Filippakopoulos et al.

NATURE (2010)

添加到收藏夹

Article Multidisciplinary Sciences

Detection of sequential polyubiquitylation on a millisecond timescale

Nathan W. Pierce et al.

NATURE (2009)

添加到收藏夹

Article Multidisciplinary Sciences

A ubiquitin ligase transfers preformed polyubiquitin chains from a conjugating enzyme to a substrate

Wei Li et al.

NATURE (2007)

添加到收藏夹

Article Biochemistry & Molecular Biology

Triterpenoid CDDO-Me blocks the NF-κB pathway by direct inhibition of IKKβ on Cys-179

Rehan Ahmad et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2006)

添加到收藏夹

Article Multidisciplinary Sciences

Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation

KM Sakamoto et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001)

添加到收藏夹

© Peeref 2019-2024. All rights reserved.