ArticleJournal of the American Chemical Society2024
Covalent Degrader of the Oncogenic Transcription Factor β-Catenin.
Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Integrated multi-omics, machine learning, network toxicology, and molecular docking reveal potential mechanisms underlying methyl 4-hydroxybenzoate-associated breast cancer.Molecular diversity · 2026Article
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- CTNNB1 mutation represents a recurrent driver molecular alteration in a subset of endometrial stromal tumors.Virchows Archiv : an international journal of pathology · 2026Article
- A Small-Molecule SLD1121 Activates Wnt/β-Catenin Signaling and Promotes Hair Growth via Targeting the Wnt Coreceptor LRP6.JACS Au · 2026Article
- Metal fluoride nanoregulators reverse therapeutic resistance via stemness remodeling to trigger pyroptosis for chemoimmunotherapy.Bioactive materials · 2026Article
- Targeting β-catenin: PROTACs and precision degraders for Wnt-driven cancers.Frontiers in oncology · 2026Review
- The Current Toolbox for Covalent Inhibitors: From Hit Identification to Drug Discovery.JACS Au · 2025Review
- Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYC.Angewandte Chemie (International ed. in English) · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Designing the Proteome with Chemical Tools: Degrons and Beyond.Chembiochem : a European journal of chemical biology · 2025Review
- Covalent Degraders of Immune Regulatory Transcription Factors IRF8 and IRF5.bioRxiv : the preprint server for biology · 2025Article
- Covalent Destabilizing Degrader of AR and AR-V7 in Androgen-Independent Prostate Cancer Cells.Journal of the American Chemical Society · 2025Article
- Chemoproteomics-EnabledJournal of the American Chemical Society · 2025Article
- Short circuit: Transcription factor addiction as a growing vulnerability in cancer.Current opinion in structural biology · 2024Review
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
β-catenin (CTNNB1) is an oncogenic transcription factor that is important in cell-cell adhesion and transcription of cell proliferation and survival genes that drive the pathogenesis of many different types of cancers. However, direct pharmacological targeting of CTNNB1 has remained challenging. Here, we have performed a screen with a library of cysteine-reactive covalent ligands to identify the monovalent degrader EN83 that depletes CTNNB1 in a ubiquitin-proteasome-dependent manner. We show that EN83 directly and covalently targets CTNNB1 three cysteines C466, C520, and C619, leading to destabilization and degradation of CTNNB1. Through structural optimization, we generate a highly potent and relatively selective destabilizing degrader that acts through the targeting of only C619 on CTNNB1. Our results show that chemoproteomic approaches can be used to covalently target and degrade challenging transcription factors like CTNNB1 through destabilization-mediated degradation.
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Registered trials
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.