Journal of Drug Metabolism & Toxicology
Open Access

David FA

Publications

• Research Article
  17-Hydroexemestane: A Potent Inhibitor of CYP19 (Aromatase) and Substrate of CYP3A
  Author(s): Landry KK, David FA and Zeruesenay DLandry KK, David FA and Zeruesenay D
  
  17-hydroexemestane is the major metabolite of exemestane in vivo. Previous studies have shown that 17-hydroexemestane is androgenic and bone protective. Due to structure similarities, we hypothesized that, like exemestane, 17-hydroexemestane is an inhibitor of aromatase (CYP19). Our aim was to assess the potency (IC50) of 17-hydroexemestane toward CYP19 inhibition, and to determine the specific CYPs responsible for 17-hydroexemestane metabolism. Using recombinant human CYP19, we investigated the ability of exemestane and 17-hydroexemestane to block the formation of estradiol from testosterone. We found that 17-hydroexemestane potently inhibited aromatase. IC 50 values for the inhibition of CYP19 by exemestane and 17-hydroexemestane were 1.5 μM and 3 μM, respectively. Furthermore, using recombinant human P450s, human liver microsomes, and HPLC analytical techniques, we identified.. View More»
  

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