ArticleACS chemical biology2017
Quantitative Chemical Proteomic Profiling of the in Vivo Targets of Reactive Drug Metabolites.
Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Beyond the Fixed Charge: A New On-Tissue Derivatisation Strategy Employing Photoionisable Chromophores for Mass Spectrometry Imaging of Amino-Containing Metabolites.Angewandte Chemie (International ed. in English) · 2026Article
- Use of new approach methodology for hepatic safety assessment of covalent inhibitor drug candidates.Toxicology research · 2025Article
- Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1.RSC chemical biology · 2023Article
- Phenelzine-based probes reveal Secernin-3 is involved in thermal nociception.Molecular and cellular neurosciences · 2023Article
- Widespread, Reversible Cysteine Modification by Methylglyoxal Regulates Metabolic Enzyme Function.ACS chemical biology · 2023Article
- Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity.Acta pharmaceutica Sinica. B · 2023Article
- Selenoprotein S: A versatile disordered protein.Archives of biochemistry and biophysics · 2022Review
- The emerging role of mass spectrometry-based proteomics in drug discovery.Nature reviews. Drug discovery · 2022Review
- Discovery and Visualization of Uncharacterized Drug-Protein Adducts Using Mass Spectrometry.Analytical chemistry · 2022Article
- Chemoproteomic interrogation of selenocysteine by low-pH isoTOP-ABPP.Methods in enzymology · 2022Article
- Your mother was right, washing matters: An alkyne-analog of ibuprofen reveals unwanted reactivity of aromatic compounds with proteins during copper-catalyzed click chemistry.Bioorganic & medicinal chemistry letters · 2021Article
- Article
- Natural Products in Cancer Therapy: Past, Present and Future.Natural products and bioprospecting · 2021Review
- Metabolic Activation of the Toxic Natural Products From Herbal and Dietary Supplements Leading to Toxicities.Frontiers in pharmacology · 2021Review
- Click Chemistry in Proteomic Investigations.Cell · 2020Review
- Chemical Biology Approaches to Interrogate the Selenoproteome.Accounts of chemical research · 2019Review
- Reactive-cysteine profiling for drug discovery.Current opinion in chemical biology · 2019Review
- Global Portrait of Protein Targets of Metabolites of the Neurotoxic Compound BIA 10-2474.ACS chemical biology · 2019Article
- Proteomics and Beyond: Cell Decision-Making Shaped by Reactive Electrophiles.Trends in biochemical sciences · 2019Review
- A Quantitative Chemoproteomic Platform to Monitor Selenocysteine Reactivity within a Complex Proteome.Cell chemical biology · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e.g., lipid/sterol pathways for troglitazone). Site-specific proteomics revealed that acetaminophen reacts with high stoichiometry with several conserved, functional (seleno)cysteine residues throughout the liver proteome. Our findings thus provide an advanced experimental framework to characterize the proteomic reactivity of drug metabolites in vivo, revealing target profiles that may help to explain mechanisms and identify risk factors for drug-induced liver injury.
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Registered trials
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