Metalloporphyrin-Catalyzed Oxidation of Sunitinib and Pazopanib, Two Anticancer Tyrosine Kinase Inhibitors: Evidence for New Potentially Toxic Metabolites Marie-Noëlle Paludetto Christian Bijani Florent Puisset Vania Bernardes-Génisson Cécile Arellano Anne Robert 10.1021/acs.jmedchem.8b00812.s002 https://acs.figshare.com/articles/dataset/Metalloporphyrin-Catalyzed_Oxidation_of_Sunitinib_and_Pazopanib_Two_Anticancer_Tyrosine_Kinase_Inhibitors_Evidence_for_New_Potentially_Toxic_Metabolites/7007888 Oxidation of two tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib, using a chemical catalytic system able to mimic the cytochrome P450 type oxidation, allowed us to prepare  putative reactive/toxic metabolites of these anticancer drugs. Among these metabolites, aromatic aldehyde derivatives were unambiguously characterized. Such biomimetic oxidation of TKI-type drugs was essential to facilitate the identification of low amounts of aldehydes generated from these TKIs when incubated with human liver microsomes (HLM), which are classical models of human hepatic metabolism. These TKI derivative aldehydes quickly react <i>in vitro</i> with amines. A similar reaction is expected to occur <i>in vivo</i> and may be at the origin of the potentially severe hepatotoxicity of these TKIs. 2018-08-13 00:00:00 Such biomimetic oxidation HLM aldehyde derivatives TKI-type drugs tyrosine kinase inhibitors Toxic Metabolites Oxidation anticancer drugs Metalloporphyrin-Catalyzed Oxidation Anticancer Tyrosine Kinase Inhibitors liver microsomes metabolite cytochrome P 450 type oxidation hepatic metabolism