Steroidal bivalent ligands for the estrogen receptor: design, synthesis, characterization and binding affinities.

Article Details

Citation

Copy to clipboard

LaFrate AL, Carlson KE, Katzenellenbogen JA

Steroidal bivalent ligands for the estrogen receptor: design, synthesis, characterization and binding affinities.

Bioorg Med Chem. 2009 May 15;17(10):3528-35. doi: 10.1016/j.bmc.2009.04.016. Epub 2009 Apr 12.

PubMed ID

19394231 [ View in PubMed

]

Abstract

Steroidal bivalent ligands for the estrogen receptor (ER) were designed using crystal structures of ERalpha dimers as a template. The syntheses of several 17alpha-ethynylestradiol-based bivalent ligands with varying linker compositions and lengths are described. The binding affinities of these bivalent ligands for ERalpha and ERbeta were determined. In the two series of bivalent ligands that we synthesized, there is a clear correlation between linker length and binding affinity, both of which reach a maximum at the same tether length. Further studies are underway to explore aspects of bivalent ligand and control compound binding to the ERs and their effects on ER dimer formation; these results will be reported in a subsequent publication.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Estradiol	Estrogen receptor alpha	Kd (nM)	0.2	N/A	N/A	Details
Estradiol	Estrogen receptor beta	Kd (nM)	0.5	N/A	N/A	Details