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• W3197705913 startingPage "114343" @default.
• W3197705913 abstract "Cabozantinib is a potent inhibitor of tyrosine kinase receptor that plays key role in tumor pathogenesis. Cabozantinib has been approved by U. S. Food and Drug Administration for the treatment of cancer. The present work was aimed to explore the in vitro metabolism of cabozantinib using liver microsomes and hepatocytes from animal species and humans through ultra-high performance liquid chromatography coupled to quadrupole/orbitrap high resolution mass spectrometer. The metabolites were characterized by their elemental compositions, MS and MS/MS spectra. As a result, a total of 26 metabolites were identified, and 15 metabolites were newly reported. Among these metabolites, M12 (oxidative defluorination), M19 and M22 (demethylation), M21 (hydroxylation) and M26 (N-oxygenation) were the major metabolites in all species. Our data revealed that cabozantinib was metabolized via the following pathways: oxidative defluorination, hydroxylation, amide hydrolysis, O-dealkylation, N-oxygenation, demethylation and glucuronidation. Human recombinant cytochrome P450 (CYP) enzyme analysis revealed that metabolism of cabozantinib was mainly catalyzed by CYP3A4, while other CYP enzymes played negligible role. The current study provided valuable metabolic data of cabozantinib from different animal species and humans, which would aid in safety and efficacy assessment." @default.
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• W3197705913 date "2021-10-01" @default.
• W3197705913 modified "2023-09-24" @default.
• W3197705913 title "Characterization of the metabolite of cabozantinib generated from liver microsomes and hepatocytes by ultra-high performance liquid chromatography coupled to quadrupole/orbitrap high resolution mass spectrometry" @default.
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• W3197705913 doi "https://doi.org/10.1016/j.jpba.2021.114343" @default.
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