ArticleNature chemical biology2025
Delineating cysteine-reactive compound modulation of cellular proteostasis processes.
Article in Nature chemical biology, 2025. 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.
- A pharmacological modality to sequester homomeric proteins.Nature chemical biology · 2026Article
- Extracellular Vesicles From Glioblastoma Cells Reflect 2D vs. 3D Culture Adaptation and Resistance to Temozolomide.Molecular & cellular proteomics : MCP · 2026Article
- Analysis of Confounding Factors in Reactive Cysteine Profiling Reveals Enhanced Chromatin-Protein Association via CDK7 Inhibition by THZ1.ACS chemical biology · 2026Article
- Scaling covalent ligand discovery through dynamic combinatorial library-versus-proteome screening.Nature communications · 2026Article
- Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules.ACS central science · 2025Article
- Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYC.Angewandte Chemie (International ed. in English) · 2025Article
- Potent Inducers of Paraptosis through Electronic Tuning of Hemicyanine Electrophiles.Journal of the American Chemical Society · 2025Article
- CySP3-96 Enables Scalable, Streamlined, and Low-Cost Sample Preparation for Cysteine Chemoproteomic Applications.Molecular & cellular proteomics : MCP · 2025Article
- KLHL23 and RhoGDI coordinate CDC42 inactivation ensuring membrane homeostasis.Nature chemical biology · 2025Article
- A Charge-Driven Strategy for Covalent Modification and Modulation of Biomolecular Condensates.Journal of the American Chemical Society · 2025Article
- 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
- Stressing out with electrophiles.Nature chemical biology · 2025Article
- Discovery of DCAF16 Binders for Targeted Protein Degradation.ACS chemical biology · 2025Article
- Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders.Journal of the American Chemical Society · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Covalent modulators and covalent degrader molecules have emerged as drug modalities with tremendous therapeutic potential. Toward realizing this potential, mass spectrometry-based chemoproteomic screens have generated proteome-wide maps of potential druggable cysteine residues. However, beyond these direct cysteine-target maps, the full scope of direct and indirect activities of these molecules on cellular processes and how such activities contribute to reported modes of action, such as degrader activity, remains to be fully understood. Using chemoproteomics, we identified a cysteine-reactive small molecule degrader of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nonstructural protein 14 (nsp14), which effects degradation through direct modification of cysteines in both nsp14 and in host protein disulfide isomerases. This degrader activity was further potentiated by generalized electrophile-induced global protein ubiquitylation, proteasome activation and widespread aggregation and depletion of host proteins, including the formation of stress granules. Collectively, we delineate the wide-ranging impacts of cysteine-reactive electrophilic compounds on cellular proteostasis processes.
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Registered trials
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