{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Jing Yang"],"species":["Acyrthosiphon Pisum"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0019537000"],"submitter_email":["yangjing@ncpsb.org.cn"],"submitter_affiliation":["State Key Laboratory of Medical Proteomics, National Center for Protein Sciences, Beijing"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"additional_accession":[]},"is_claimable":false,"name":"A Quantitative Chemoproteomics Platform to Interrogate Metabolic Activation of Furan-Containing Herbal Medicines","description":"In this work, we extend our previously reported clickable γ-dicarbonyl probe ONAyne to exogenous natural products and establish a competitive activity-based protein profiling (ABPP) platform for furan-containing herbal constituents. In mouse liver microsomes, the platform captured, at site level and proteome scale, covalent modification of key lysine residues on Cyp1a2, Cyp2e1 and Cyp3a11 by the bioactivated metabolites of limonin, obacunone and fraxinellone. Enzyme kinetic analysis demonstrated that all three compounds act as time- and concentration-dependent mechanism-based inactivators of these P450 enzymes, and repeated oral administration of the three herbal ethanol extracts in mice significantly inhibited hepatic Cyp3a and Cyp2e1 activities, validating the findings in vivo. Together, these results connect metabolic activation, covalent target identification and functional enzyme inactivation into a complete mechanistic chain, providing a transferable chemical-biology platform for hepatotoxicity assessment of furan-containing herbal medicines and for early prediction of herb–drug interaction risk.","dates":{"publication":"Sat Sep 12 00:00:00 BST 2026"},"accession":"PXD084125","cross_references":{"TAXONOMY":["7029"]}}