Identification of reactive intermediate formation and bioactivation pathways in Abemaciclib metabolism by LC-MS/MS: in vitro metabolic investigation.

ABSTRACT: Abemaciclib (Verzenio^®) is approved as a tyrosine kinase inhibitor (TKI) for breast cancer treatment. In this study, in vitro phase I metabolic profiling of Abemaciclib (ABC) was done using rat liver microsomes (RLMs). We checked the formation of reactive intermediates in ABC metabolism using RLMs in the presence of potassium cyanide (KCN) that was used as a capturing agent for iminium reactive intermediates forming a stable complex that can be characterized by LC-MS/MS. Nine in vitro phase I metabolites and three cyano adducts were identified. The metabolic reactions involved in the formation of these metabolites and adducts are reduction, oxidation, hydroxylation and cyanide addition. The bioactivation pathway was also proposed. Knowing the electrodeficient bioac

SUBMITTER: Kadi AA 

PROVIDER: S-EPMC6366225 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature