Abstract
A qualitative 3D pharmacophore model (a common feature based model or Catalyst HipHop algorithm) was developed for well-known natural product androgen receptor down-regulating agents (ARDAs). The four common chemical features identified included: one hydrophobic group, one ring aromatic group, and two hydrogen bond acceptors. This model served as a template in virtual screening of the Maybridge and NCI databases that resulted in identification of six new ARDAs (EC(50) values 17.5-212 microM). Five of these molecules strongly inhibited the growth of human prostate LNCaP cells. These novel compounds may be used as leads to develop other novel anti-prostate cancer agents.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Androgen Antagonists / chemical synthesis*
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Androgen Antagonists / pharmacology*
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Androgen Receptor Antagonists*
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Blotting, Western
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Catalysis
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Cell Line, Tumor
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Computational Biology
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Databases, Factual
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Dose-Response Relationship, Drug
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Down-Regulation / drug effects
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Humans
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Male
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Models, Molecular
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Neoplasm Proteins / chemical synthesis
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Neoplasm Proteins / pharmacology
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / pathology
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Structure-Activity Relationship
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Tetrazolium Salts
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Thiazoles
Substances
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Androgen Antagonists
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Androgen Receptor Antagonists
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Antineoplastic Agents
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Neoplasm Proteins
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Tetrazolium Salts
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Thiazoles
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thiazolyl blue