Differential response of estrogen receptor subtypes to 1,3-diarylindene and 2,3-diarylindene ligands.
Article Details
- CitationCopy to clipboard
Clegg NJ, Paruthiyil S, Leitman DC, Scanlan TS
Differential response of estrogen receptor subtypes to 1,3-diarylindene and 2,3-diarylindene ligands.
J Med Chem. 2005 Sep 22;48(19):5989-6003.
- PubMed ID
- 16162002 [ View in PubMed]
- Abstract
Estrogen 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Estradiol Estrogen receptor alpha EC 50 (nM) 0.019 N/A N/A Details Estradiol Estrogen receptor beta EC 50 (nM) 0.098 N/A N/A Details Raloxifene Estrogen receptor alpha Ki (nM) 0.03 N/A N/A Details Raloxifene Estrogen receptor beta Ki (nM) 4.5 N/A N/A Details