Abstract
We report the synthesis of novel steroidal androgen receptor ligands comprising 11beta-alkyl-Delta(9)-derivatives of 19-nortestosterone. These compounds are structurally related to the antiprogestin, antiglucocorticoid, and antiandrogen drug mifepristone (RU486). Nortestosterone analogues bearing 11beta-octyl and 11beta-decyl side-chains bind tightly to recombinant AR protein (IC(50) = 6.6 nM and IC(50) = 0.8 nM), block AR dimerization, exhibit activity against LNCaP prostate cancer cells, and comprise partial AR agonists with low antiglucocorticoid activity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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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Androgens*
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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CHO Cells
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Cell Line, Tumor
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Cricetinae
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Cyproterone Acetate / pharmacology
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Dimerization
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Humans
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Ligands
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Male
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Mifepristone / pharmacology
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Nandrolone / analogs & derivatives*
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Nandrolone / chemical synthesis*
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Nandrolone / pharmacology
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Prostatic Neoplasms
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Receptors, Androgen / chemistry
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Structure-Activity Relationship
Substances
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Androgen Antagonists
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Androgen Receptor Antagonists
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Androgens
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Antineoplastic Agents
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Ligands
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Receptors, Androgen
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Mifepristone
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Cyproterone Acetate
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Nandrolone