Abstract
A strategy to obtain a fully orthogonal estrogen-receptor-based gene switch responsive to molecules with acceptable pharmacological properties is presented. From a series of tetrahydrofluorenones active on the wild-type estrogen receptor (ER) an inactive analogue is chosen as a new lead compound. Coevolution of receptor mutants and ligands leads to an ER-based gene switch suitable for studies in animal models.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Estradiol / chemistry
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Estrogen Receptor alpha / drug effects
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Estrogen Receptor alpha / genetics
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Estrogen Receptor beta / drug effects
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Estrogen Receptor beta / genetics
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Fluorenes / chemical synthesis*
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Fluorenes / chemistry
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Fluorenes / pharmacology
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HeLa Cells
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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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Mutation
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Receptors, Estrogen / drug effects*
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Receptors, Estrogen / genetics
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Structure-Activity Relationship
Substances
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Fluorenes
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Ligands
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Receptors, Estrogen
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Estradiol