Belizatinib: Novel reactive intermediates and bioactivation pathways characterized by LC-MS/MS.

08:00 EDT 6th April 2019 | BioPortfolio

Summary of "Belizatinib: Novel reactive intermediates and bioactivation pathways characterized by LC-MS/MS."

Belizatinib (BZB; TSR-011) is a next-generation anaplastic lymphoma kinase inhibitor that also inhibits tropomyosin-related kinases A/B/C. In this in-vitro study, we examined the formation of reactive metabolites from BZB using rat liver microsomes or human liver microsomes in the presence of a trapping agent (potassium cyanide) to generate iminium reactive intermediates. Identification of the in vitro BZB metabolites indicated that the major in-vitro metabolic reaction involved hydroxylation of the piperidine moiety. We identified eight in-vitro phase I metabolites and three iminium reactive intermediates, suggesting two possible BZB-bioactivation pathways. We propose that the tertiary nitrogen in the piperidine ring activates the attached benzyl carbon in addition to the two α carbons inside the ring. To our knowledge, this is the first report on the structural identification of reactive metabolites derived from BZB.


Journal Details

This article was published in the following journal.

Name: Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Pages: 132-147


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