Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta

Michael Waibel, Meri De Angelis, Fabio Stossi, Karen J. Kieser, Kathryn E. Carlson, Benita S Katzenellenbogen, John A. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

A series of structurally simple bibenzyl-diol and stilbene-diol core molecules, structural analogs of the well-known hexestrol and diethylstilbestrol non-steroidal estrogens, were prepared and evaluated as estrogen receptor (ER) subtype-selective ligands. Analysis of their ERα and ERβ binding showed that certain substitution patterns engendered binding affinities that were >100-fold selective for ERβ. When further investigated in cell-based gene transcription assays, some molecules showed similarly high relative transcriptional potency selectivity in favor of ERβ. Interestingly, the most ERβ-selective molecules were those bearing non-polar substituents on one of the internal carbon atoms. These compounds should be useful probes for determining the physiological roles of ERβ, and they might lead to the development of more selective and thus safer pharmaceuticals.

Original languageEnglish (US)
Pages (from-to)3412-3424
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number9
DOIs
StatePublished - Sep 1 2009

Fingerprint

Stilbenes
Estrogen Receptor beta
Estrogen Receptors
Ligands
Atoms
Molecules
Hexestrol
Non-Steroidal Estrogens
Bearings (structural)
Diethylstilbestrol
Transcription
Assays
Substitution reactions
Carbon
Genes
Pharmaceutical Preparations

Keywords

  • Estrogen receptor
  • Estrogen receptor beta
  • Hexestrol
  • Selective ligand
  • Stilbestrol

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta. / Waibel, Michael; De Angelis, Meri; Stossi, Fabio; Kieser, Karen J.; Carlson, Kathryn E.; Katzenellenbogen, Benita S; Katzenellenbogen, John A.

In: European Journal of Medicinal Chemistry, Vol. 44, No. 9, 01.09.2009, p. 3412-3424.

Research output: Contribution to journalArticle

Waibel, Michael ; De Angelis, Meri ; Stossi, Fabio ; Kieser, Karen J. ; Carlson, Kathryn E. ; Katzenellenbogen, Benita S ; Katzenellenbogen, John A. / Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta. In: European Journal of Medicinal Chemistry. 2009 ; Vol. 44, No. 9. pp. 3412-3424.
@article{b979c10029c4478eb3801a1dc1221c3a,
title = "Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta",
abstract = "A series of structurally simple bibenzyl-diol and stilbene-diol core molecules, structural analogs of the well-known hexestrol and diethylstilbestrol non-steroidal estrogens, were prepared and evaluated as estrogen receptor (ER) subtype-selective ligands. Analysis of their ERα and ERβ binding showed that certain substitution patterns engendered binding affinities that were >100-fold selective for ERβ. When further investigated in cell-based gene transcription assays, some molecules showed similarly high relative transcriptional potency selectivity in favor of ERβ. Interestingly, the most ERβ-selective molecules were those bearing non-polar substituents on one of the internal carbon atoms. These compounds should be useful probes for determining the physiological roles of ERβ, and they might lead to the development of more selective and thus safer pharmaceuticals.",
keywords = "Estrogen receptor, Estrogen receptor beta, Hexestrol, Selective ligand, Stilbestrol",
author = "Michael Waibel and {De Angelis}, Meri and Fabio Stossi and Kieser, {Karen J.} and Carlson, {Kathryn E.} and Katzenellenbogen, {Benita S} and Katzenellenbogen, {John A.}",
year = "2009",
month = "9",
day = "1",
doi = "10.1016/j.ejmech.2009.02.006",
language = "English (US)",
volume = "44",
pages = "3412--3424",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
number = "9",

}

TY - JOUR

T1 - Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta

AU - Waibel, Michael

AU - De Angelis, Meri

AU - Stossi, Fabio

AU - Kieser, Karen J.

AU - Carlson, Kathryn E.

AU - Katzenellenbogen, Benita S

AU - Katzenellenbogen, John A.

PY - 2009/9/1

Y1 - 2009/9/1

N2 - A series of structurally simple bibenzyl-diol and stilbene-diol core molecules, structural analogs of the well-known hexestrol and diethylstilbestrol non-steroidal estrogens, were prepared and evaluated as estrogen receptor (ER) subtype-selective ligands. Analysis of their ERα and ERβ binding showed that certain substitution patterns engendered binding affinities that were >100-fold selective for ERβ. When further investigated in cell-based gene transcription assays, some molecules showed similarly high relative transcriptional potency selectivity in favor of ERβ. Interestingly, the most ERβ-selective molecules were those bearing non-polar substituents on one of the internal carbon atoms. These compounds should be useful probes for determining the physiological roles of ERβ, and they might lead to the development of more selective and thus safer pharmaceuticals.

AB - A series of structurally simple bibenzyl-diol and stilbene-diol core molecules, structural analogs of the well-known hexestrol and diethylstilbestrol non-steroidal estrogens, were prepared and evaluated as estrogen receptor (ER) subtype-selective ligands. Analysis of their ERα and ERβ binding showed that certain substitution patterns engendered binding affinities that were >100-fold selective for ERβ. When further investigated in cell-based gene transcription assays, some molecules showed similarly high relative transcriptional potency selectivity in favor of ERβ. Interestingly, the most ERβ-selective molecules were those bearing non-polar substituents on one of the internal carbon atoms. These compounds should be useful probes for determining the physiological roles of ERβ, and they might lead to the development of more selective and thus safer pharmaceuticals.

KW - Estrogen receptor

KW - Estrogen receptor beta

KW - Hexestrol

KW - Selective ligand

KW - Stilbestrol

UR - http://www.scopus.com/inward/record.url?scp=67650430010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650430010&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2009.02.006

DO - 10.1016/j.ejmech.2009.02.006

M3 - Article

C2 - 19286283

AN - SCOPUS:67650430010

VL - 44

SP - 3412

EP - 3424

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

IS - 9

ER -