ArticleCell chemical biology2017
Covalent Ligand Discovery against Druggable Hotspots Targeted by Anti-cancer Natural Products.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 134 citations in OpenAlex.
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- The Current Toolbox for Covalent Inhibitors: From Hit Identification to Drug Discovery.JACS Au · 2025Review
- CySP3-96 Enables Scalable, Streamlined, and Low-Cost Sample Preparation for Cysteine Chemoproteomic Applications.Molecular & cellular proteomics : MCP · 2025Article
- Covalent Degraders of Immune Regulatory Transcription Factors IRF8 and IRF5.bioRxiv : the preprint server for biology · 2025Article
- Chemoproteomics reveals proteome-wide covalent and non-covalent targets of withaferin A.Acta pharmacologica Sinica · 2025Article
- Delineating cysteine-reactive compound modulation of cellular proteostasis processes.Nature chemical biology · 2025Article
- Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.Cell death and differentiation · 2024Article
- Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold.Nature communications · 2024Article
- Multi-tiered chemical proteomic maps of tryptoline acrylamide-protein interactions in cancer cells.Nature chemistry · 2024Article
- Targeted Protein Localization by Covalent 14-3-3 Recruitment.Journal of the American Chemical Society · 2024Article
- Natural Product-Inspired Molecules for Covalent Inhibition of SHP2 Tyrosine Phosphatase.Tetrahedron · 2024Article
- Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders.Journal of the American Chemical Society · 2024Article
- Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.Research square · 2024Article
- Covalent Targeting of Glutamate Cysteine Ligase to Inhibit Glutathione Synthesis.Chembiochem : a European journal of chemical biology · 2023Article
- Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds.bioRxiv : the preprint server for biology · 2023Article
- Covalent 14-3-3 Molecular Glues and Heterobifunctional Molecules Against Nuclear Transcription Factors and Regulators.bioRxiv : the preprint server for biology · 2023Article
- GPX4 in cell death, autophagy, and disease.Autophagy · 2023Review
- Multi-omic stratification of the missense variant cysteinome.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Many natural products that show therapeutic activities are often difficult to synthesize or isolate and have unknown targets, hindering their development as drugs. Identifying druggable hotspots targeted by covalently acting anti-cancer natural products can enable pharmacological interrogation of these sites with more synthetically tractable compounds. Here, we used chemoproteomic platforms to discover that the anti-cancer natural product withaferin A targets C377 on the regulatory subunit PPP2R1A of the tumor-suppressor protein phosphatase 2A (PP2A) complex leading to activation of PP2A activity, inactivation of AKT, and impaired breast cancer cell proliferation. We developed a more synthetically tractable cysteine-reactive covalent ligand, JNS 1-40, that selectively targets C377 of PPP2R1A to impair breast cancer signaling, proliferation, and in vivo tumor growth. Our study highlights the utility of using chemoproteomics to map druggable hotspots targeted by complex natural products and subsequently interrogating these sites with more synthetically tractable covalent ligands 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.