Abstract
A new class of potent farnesyltransferase inhibitors based on a 1,4-diazepane scaffold was synthesized with protein farnesyltransferase inhibition potencies in the low nanomolar range. The compounds block the growth on two hormone-resistant tumor prostatic cell lines (DU145 and PC3). The advanced cellular evaluation of the more potent farnesyltransferase inhibitors was explored and revealed a disorganization of tubulin in PC3 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androgen Antagonists / therapeutic use*
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Azepines / chemical synthesis*
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Azepines / pharmacokinetics
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Azepines / pharmacology
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Cell Line
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Cell Line, Tumor
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Drug Resistance, Neoplasm
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Drug Screening Assays, Antitumor
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Farnesyltranstransferase / antagonists & inhibitors*
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Humans
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Hydrophobic and Hydrophilic Interactions
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Male
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Models, Molecular
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Prostatic Neoplasms / drug therapy*
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Structure-Activity Relationship
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Tubulin / drug effects
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Tubulin / ultrastructure
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Tubulin Modulators / chemical synthesis*
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Tubulin Modulators / pharmacokinetics
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Tubulin Modulators / pharmacology
Substances
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1,4-diazepane
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Androgen Antagonists
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Azepines
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Tubulin
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Tubulin Modulators
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Farnesyltranstransferase