Impact of nonsynonymous single nucleotide polymorphisms on in-vitro metabolism of exemestane by hepatic cytosolic reductases.

ABSTRACT:

Objective

Exemestane (EXE) is a potent third-generation aromatase inhibitor used as endocrine therapy in breast cancer treatment and prevention. Characterization of its metabolic pathway is incomplete, with ambiguity existing in the identity of enzymes driving the production of its key metabolite, 17β-dihydroexemestane (17β-DHE). The impact of genetic variation on EXE metabolism is also unknown. This study aims to describe cytosolic reductase involvement in hepatic EXE metabolism and to assess the impact of functional polymorphisms on metabolite production.

Materials and methods

Phase I metabolites were identified in incubations of EXE with pooled human liver cytosol or recombinant protein for AKR1Cs and CBR1. Kinetic parameters characterizing EXE reduction were measured for

SUBMITTER: Platt A 

PROVIDER: S-EPMC5088049 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature