First Dual Aromatase-Steroid Sulfatase Inhibitors

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 aromata...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2003-07, Vol.46 (15), p.3193-3196
Main Authors: Woo, L. W. Lawrence, Sutcliffe, Oliver B, Bubert, Christian, Grasso, Anna, Chander, Surinder K, Purohit, Atul, Reed, Michael J, Potter, Barry V. L
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Aromatase Inhibitors
Arylsulfatases - antagonists & inhibitors
Biological and medical sciences
Cell Line
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Estradiol - analysis
Estradiol - blood
Estrogen Antagonists - chemical synthesis
Estrogen Antagonists - chemistry
Estrogen Antagonists - pharmacology
Female
General aspects
Humans
Liver - chemistry
Medical sciences
Pharmacology. Drug treatments
Rats
Rats, Wistar
Steryl-Sulfatase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm034033b