Protein-structure-based prediction of animal model suitability for pharmacodynamic studies of subtype-selective estrogens.

Subtype-selective estrogens are of increasing importance as tools used to unravel physiological roles of the estrogen receptors, ERalpha and ERbeta, in various species. Although human ERalpha and ERbeta differ by only two amino acids within the binding pockets, we and others recently succeeded in generating subtype-selective agonists. We have proposed that the selectivity of the steroidal compounds 16alpha-lactone-estradiol (16alpha-LE(2), hERalpha selective) and 8beta-vinyl-estradiol (8beta-VE(2), hERbeta selective) is based on the interaction of certain substituents of these compounds with essentially one amino acid in the respective ER binding pockets.