Abstract
Efforts to limit the metabolic alteration of the aminoalkyl side chain of tamoxifen by fluorination largely decrease its ER-mediated antagonistic properties in MCF-7 cells (i.e., ability to inhibit growth, to stabilize ER, and to modulate ERE and AP-1 transcriptional activity). This loss is associated with an enhancement of agonistic activity. Loss of interaction between Asp 351 and the nitrogen atom of tamoxifen provoked by the fluorination of its side chain may explain this property.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Estrogen Antagonists / chemical synthesis*
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Estrogen Antagonists / chemistry
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Estrogen Antagonists / pharmacology*
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Fluorine / chemistry*
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Humans
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Methylation
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Molecular Structure
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism
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Structure-Activity Relationship
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Tamoxifen / chemical synthesis
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Tamoxifen / chemistry*
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Tamoxifen / pharmacology*
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Transcription Factor AP-1 / metabolism
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Transcription, Genetic / drug effects
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Transcription, Genetic / genetics
Substances
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Estrogen Antagonists
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Receptors, Estrogen
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Transcription Factor AP-1
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Tamoxifen
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Fluorine