First dual aromatase-steroid sulfatase inhibitors

L.W.L. Woo, O.B. Sutcliffe, C. Bubert, A. Grasso, S.K. Chander, A. Purohit, M.J. Reed, B.V.L. Potter

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Abstract

Aromatase inhibitors in clinical use block the biosynthesis of estrogens. Hydrolysis of estrone 3-sulfate by steroid sulfatase is an important additional source of tumor estrogen, and blockade of both enzymes should provide a more effective endocrine therapy. Sulfamoylated derivatives of the aromatase inhibitor YM511 inhibited sulfatase and aromatase in JEG-3 cells with respective IC50 values of 20-227 and 0.82-100 nM (cf. letrozole, 0.89 nM). One dual inhibitor was potent against both enzymes in vivo, validating the concept.
Original languageEnglish
Pages (from-to)3193-3196
Number of pages3
JournalJournal of Medicinal Chemistry
Volume46
Issue number15
DOIs
Publication statusPublished - 2003

Keywords

  • breast carcinoma
  • endocrine therapy
  • cancer research

Cite this

Woo, L. W. L., Sutcliffe, O. B., Bubert, C., Grasso, A., Chander, S. K., Purohit, A., Reed, M. J., & Potter, B. V. L. (2003). First dual aromatase-steroid sulfatase inhibitors. Journal of Medicinal Chemistry, 46(15), 3193-3196. https://doi.org/10.1021/jm034033b