The nature of the ligand-binding pocket of estrogen receptor alpha
and beta: The search for subtype-selective ligands and implications
for the prediction of estrogenic activity
J. A. Katzenellenbogen, R. Muthyala, and B. S. Katzenellenbogen
Departments of Chemistry, Molecular and Integrative
Physiology, University of Illinois, Urbana, IL 61801, USA
Abstract: The ligand-binding pockets of estrogen receptor alpha
and beta (ERa and ERb)
appear to have subpockets of different size and flexibility. To find
ligands that will discriminate between the two ER subtypes on the basis
of affinity or efficacy, we have prepared compounds of varying size,
shape and structure. We have evaluated the binding affinity of these
compounds and their potency and efficacy as transcriptional activators
through ERa and ERb.
In this manner, we have identified a number of ligands that show pronounced
ER subtype selectivity. These studies also highlight the eclectic structure–activity
relationships of estrogens and the challenges inherent in developing
computational methods for the prediction of estrogenic activity.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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