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PMID: 15857113 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and ERRgamma.

Journal of medicinal chemistry ·Vol. 48 ·No. 9 ·2005-05-05 ·Pages 3107-9

Zuercher WJ, Gaillard S, Orband-Miller LA, Chao EY, Shearer BG, Jones DG, Miller AB, Collins JL, McDonnell DP, Willson TM

Abstract

The first small molecule agonists of the estrogen-related receptors have been identified. GSK4716 (3) and GSK9089 (4) show binding to ERRgamma with remarkable selectivity over the classical estrogen receptors. Notably, in cell-based reporter assays, 3 mimics the protein ligand PGC-1alpha in activation of human ERRbeta and ERRgamma.

MeSH Terms

Binding, Competitive Estrogen Receptor beta/agonists,genetics Fluorescence Resonance Energy Transfer Genes, Reporter HeLa Cells Heat-Shock Proteins/biosynthesis Humans Hydrazines/chemical synthesis,chemistry,pharmacology Ligands Molecular Mimicry Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Phenols/chemical synthesis,chemistry,pharmacology Receptors, Estrogen/agonists,genetics Structure-Activity Relationship Transcription Factors/biosynthesis

Chemicals

Estrogen Receptor beta Heat-Shock Proteins Hydrazines Ligands PPARGC1A protein, human Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Phenols Receptors, Estrogen Transcription Factors estrogen receptor gamma

Authors & Affiliations

10 authors, click to expand affiliations / ORCID

Zuercher William J

Discovery Research, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27707, USA. william.j.zuercher@gsk.com

Gaillard Stéphanie

Orband-Miller Lisa A

Chao Esther Y H

Shearer Barry G

Jones David G

Miller Aaron B

Collins Jon L

McDonnell Donald P

Willson Timothy M

Article Info

Journal

Journal of medicinal chemistry

Abbr.

J Med Chem

ISSN

0022-2623

DOI

10.1021/jm050161j

william.j.zuercher@gsk.com

Published

2005-05-05

Pages

3107-9

Language

English

Region

United States

NLM ID

9716531

Subset

Grants

NIDDK NIH HHS · U19 DK062434 · United States

External Links

PubMed source DOI: 10.1021/jm050161j View journal details

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Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and ERRgamma.

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