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

Research output: Contribution to journalArticle

70 Citations (Scopus)

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

Fingerprint

Steryl-Sulfatase
Aromatase Inhibitors
Aromatase
letrozole
Estrogens
Sulfatases
Enzymes
Inhibitory Concentration 50
Hydrolysis
Neoplasms
Therapeutics

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., ... 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
Woo, L.W.L. ; Sutcliffe, O.B. ; Bubert, C. ; Grasso, A. ; Chander, S.K. ; Purohit, A. ; Reed, M.J. ; Potter, B.V.L. / First dual aromatase-steroid sulfatase inhibitors. In: Journal of Medicinal Chemistry. 2003 ; Vol. 46, No. 15. pp. 3193-3196.
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Woo, LWL, Sutcliffe, OB, Bubert, C, Grasso, A, Chander, SK, Purohit, A, Reed, MJ & Potter, BVL 2003, 'First dual aromatase-steroid sulfatase inhibitors', Journal of Medicinal Chemistry, vol. 46, no. 15, pp. 3193-3196. https://doi.org/10.1021/jm034033b

First dual aromatase-steroid sulfatase inhibitors. / Woo, L.W.L.; Sutcliffe, O.B.; Bubert, C.; Grasso, A.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V.L.

In: Journal of Medicinal Chemistry, Vol. 46, No. 15, 2003, p. 3193-3196.

Research output: Contribution to journalArticle

TY - JOUR

T1 - First dual aromatase-steroid sulfatase inhibitors

AU - Woo, L.W.L.

AU - Sutcliffe, O.B.

AU - Bubert, C.

AU - Grasso, A.

AU - Chander, S.K.

AU - Purohit, A.

AU - Reed, M.J.

AU - Potter, B.V.L.

PY - 2003

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AB - 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.

KW - breast carcinoma

KW - endocrine therapy

KW - cancer research

UR - http://dx.doi.org/10.1021/jm034033b

U2 - 10.1021/jm034033b

DO - 10.1021/jm034033b

M3 - Article

VL - 46

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EP - 3196

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 15

ER -

Woo LWL, Sutcliffe OB, Bubert C, Grasso A, Chander SK, Purohit A et al. First dual aromatase-steroid sulfatase inhibitors. Journal of Medicinal Chemistry. 2003;46(15):3193-3196. https://doi.org/10.1021/jm034033b