Abstract
The design and synthesis of 4-hydroxytamoxifen (4-OHT) derivatives are described. The binding affinities of these compounds toward the orphan estrogen-related receptor gamma and the classical estrogen receptor alpha demonstrate that analogs bearing hydroxyalkyl groups display improved binding selectivity profiles compared with that of 4-OHT. An X-ray crystal structure of one of the designed compounds bound to ERRgamma LBD confirms the molecular basis of the selectivity.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Binding Sites / drug effects
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Crystallography, X-Ray
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Drug Design
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Estrogen Receptor alpha / drug effects
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Humans
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Ligands
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Models, Molecular
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Molecular Structure
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Receptors, Cytoplasmic and Nuclear / drug effects*
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Receptors, Estrogen / drug effects*
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Structure-Activity Relationship
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Tamoxifen* / analogs & derivatives
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Tamoxifen* / chemical synthesis
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Tamoxifen* / pharmacology
Substances
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ESRRG protein, human
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Estrogen Receptor alpha
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Ligands
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Receptors, Cytoplasmic and Nuclear
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Receptors, Estrogen
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Tamoxifen