ArticleChemical communications (Cambridge, England)2017
Chemoproteomics-enabled covalent ligand screen reveals a cysteine hotspot in reticulon 4 that impairs ER morphology and cancer pathogenicity.
Article in Chemical communications (Cambridge, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 80 citations in OpenAlex.
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- Activity-based protein profiling guided new target identification of quinazoline derivatives for expediting bactericide discovery: Activity-based protein profiling derived new target discovery of antibacterial quinazolines.Journal of advanced research · 2025Article
- Identification of Nogo-B as a potential therapeutic target of osteosarcoma via stereochemically selective covalent probes.Cell death & disease · 2025Article
- Chemical Proteomics-Guided Discovery of Covalent Ligands for Cancer Proteins.Annual review of cancer biology · 2024Article
- Covalent Targeting of Glutamate Cysteine Ligase to Inhibit Glutathione Synthesis.Chembiochem : a European journal of chemical biology · 2023Article
- Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes.Cells · 2023Article
- Cellular Exposure to Chloroacetanilide Herbicides Induces Distinct Protein Destabilization Profiles.ACS chemical biology · 2023Article
- N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics.Nature communications · 2023Article
- E3 Ligases Meet Their Match: Fragment-Based Approaches to Discover New E3 Ligands and to Unravel E3 Biology.Journal of medicinal chemistry · 2023Review
- Proteome-Wide Fragment-Based Ligand and Target Discovery.Israel journal of chemistry · 2023Article
- Ligandability of E3 Ligases for Targeted Protein Degradation Applications.Biochemistry · 2023Review
- The putative oncogenic role of WDTC1 in colorectal cancer.Carcinogenesis · 2022Article
- Deubiquitinase-targeting chimeras for targeted protein stabilization.Nature chemical biology · 2022Article
- Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC.Cell chemical biology · 2021Article
- Covalent-Fragment Screening of BRD4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites.ACS chemical biology · 2020Article
- Click Chemistry in Proteomic Investigations.Cell · 2020Review
- The McKenna reaction - avoiding side reactions in phosphonate deprotection.Beilstein journal of organic chemistry · 2020Article
- Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications.ACS chemical biology · 2019Article
- Covalent targeting of the vacuolar HNature chemical biology · 2019Article
- Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells.Cell chemical biology · 2019Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Chemical genetics has arisen as a powerful approach for identifying novel anti-cancer agents. However, a major bottleneck of this approach is identifying the targets of lead compounds that arise from screens. Here, we coupled the synthesis and screening of fragment-based cysteine-reactive covalent ligands with activity-based protein profiling (ABPP) chemoproteomic approaches to identify compounds that impair colorectal cancer pathogenicity and map the druggable hotspots targeted by these hits. Through this coupled approach, we discovered a cysteine-reactive acrylamide DKM 3-30 that significantly impaired colorectal cancer cell pathogenicity through targeting C1101 on reticulon 4 (RTN4). While little is known about the role of RTN4 in colorectal cancer, this protein has been established as a critical mediator of endoplasmic reticulum tubular network formation. We show here that covalent modification of C1101 on RTN4 by DKM 3-30 or genetic knockdown of RTN4 impairs endoplasmic reticulum and nuclear envelope morphology as well as colorectal cancer pathogenicity. We thus put forth RTN4 as a potential novel colorectal cancer therapeutic target and reveal a unique druggable hotspot within RTN4 that can be targeted by covalent ligands to impair colorectal cancer pathogenicity. Our results underscore the utility of coupling the screening of fragment-based covalent ligands with isoTOP-ABPP platforms for mining the proteome for novel druggable nodes that can be targeted for cancer therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.