Title : Metabolism-dependent inhibition of CYP3A4 by lapatinib: evidence for formation of a metabolic intermediate complex with a nitroso/oxime metabolite formed via a nitrone intermediate.

Pub. Date : 2013 May

PMID : 23404373






2 Functional Relationships(s)
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1 The abundance of one metabolite, the N-dealkylated nitroso/oxime lapatinib metabolite (M9), correlated directly with the prevalence or the disruption of the MI complex with CYP3A4. Nitrogen cytochrome P450 family 3 subfamily A member 4 Homo sapiens
2 Our findings support the mechanism of lapatinib CYP3A4 inactivation as MI complex formation with the nitroso metabolite formed through the secondary hydroxylamine and nitrone pathway, rather than by N-dealkylation to the primary amine followed by N-hydroxylation and dehydrogenation as is usually assumed. Nitrogen cytochrome P450 family 3 subfamily A member 4 Homo sapiens