Novel inhibitors of 17β-hydroxysteroid dehydrogenase type 1:: Templates for design

被引：40

作者：

Allan, Gillian M. ^{[1
,2
]}

Vicker, Nigel ^{[1
,2
]}

Lawrence, Harshani R. ^{[1
,2
]}

Tutill, Helena J. ^{[3
]}

Day, Joanna M. ^{[3
]}

Huchet, Marion ^{[4
]}

Ferrandis, Eric ^{[4
]}

Reed, Michael J. ^{[3
]}

Purohit, Atul ^{[3
]}

Potter, Barry V. L. ^{[1
,2
]}

机构：

[1] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England

[2] Univ Bath, Sterix Ltd, Bath BA2 7AY, Avon, England

[3] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Fac Med, Endocrinol & Metab Med & Sterix Ltd, London W2 1NY, England

[4] IPSEN Syst Biol, F-91966 Les Ulis, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 08期

关键词：

hydroxysteroid dehydrogenase; 17; beta-HSD1; beta-HSD2; breast cancer;

D O I：

10.1016/j.bmc.2008.02.059

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) catalyze the interconversion between the oxidized and reduced forms of androgens and estrogens at the 17 position. The 17 beta-HSD type 1 enzyme (17 beta-HSD1) catalyzes the reduction of estrone (E1) to estradiol and is expressed in malignant breast cells. Inhibitors of this enzyme thus have potential as treatments for hormone dependent breast cancer. Syntheses and biological evaluation of novel non-steroidal inhibitors designed to mimic the E1 template are reported using information from potent steroidal inhibitors. Of the templates investigated biphenyl ethanone was promising and led to inhibitors with IC50 values in the low micromolar range. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4438 / 4456

页数：19

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