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pubmed-article:16162002pubmed:abstractTextEstrogen receptors (ERs) control transcription of genes important for normal human development and reproduction. The signaling networks are complex, and there is a need for a molecular level understanding of the roles of receptor subtypes ERalpha and ERbeta in normal physiology and as therapeutic targets. We synthesized two series of ER ligands, based on a common indene scaffold, in an attempt to develop compounds that can selectively modulate ER-mediated transcription. The 3-ethyl-1,2-diarylindenes, utilizing an amide linker for the 1-aryl extension, bind weakly to the ERs. The 2,3-diarylindenes bind with high affinity to the ER subtypes and demonstrate a range of different biological activities, both in transcriptional reporter gene assays and inhibition of estradiol-stimulated proliferation of MCF-7 cells. Several ligands differentiate between ERalpha and ERbeta subtypes at an estrogen response element (ERE), displaying various levels of partial to full agonist activity at ERalpha, while antagonizing estradiol action at ERbeta.lld:pubmed
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pubmed-article:16162002pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:16162002pubmed:articleTitleDifferential response of estrogen receptor subtypes to 1,3-diarylindene and 2,3-diarylindene ligands.lld:pubmed
pubmed-article:16162002pubmed:affiliationChemistry and Chemical Biology Graduate Program, Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, USA.lld:pubmed
pubmed-article:16162002pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:16162002pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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pubmed-article:16162002pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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