A structural explanation for ERalpha/ERbeta SERM discrimination.

G L Greene; A K Shiau; K W Nettles

doi:10.1007/978-3-662-05386-7_3

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A structural explanation for ERalpha/ERbeta SERM discrimination.

G L Greene·A K Shiau·K W Nettles

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Abstract

Many NRs have multiple subtypes that possess distinct expression patterns and that regulate distinct target genes. Antagonists generated through the addition of bulky side chains to agonist scaffolds are limited to being antagonistic on one or more subtypes of a particular NR. The passive antagonism mechanism, as revealed in our studies through direct comparison of the two THC-ER LBD complexes, suggests a new approach to achieving NR antagonism. Compounds could be designed to selectively stabilize the inactive conformations of certain NR subtypes and the active conformations of others. Such ligands are likely to exert novel biological and therapeutic effects.

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Animals Estrogen Receptor alpha Estrogen Receptor beta Humans Models, Molecular Protein Conformation Receptors, Estrogen Selective Estrogen Receptor Modulators Structure-Activity Relationship Journal Article Review

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G L Greene, A K Shiau, K W Nettles. 2004. A structural explanation for ERalpha/ERbeta SERM discrimination.. https://doi.org/10.1007/978-3-662-05386-7_3

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