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Updated: Jul 16, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Effects of steroidal and non-steroidal antiandrogens on wild-type and mutant androgen receptors

Masayasu Urushibara1, Junichiro Ishioka, Nobuhiko Hyochi

  • 1Department of Urology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.

The Prostate
|March 22, 2007
PubMed
Abstract

Insights

Switching antiandrogens may be effective for prostate cancer patients with mutant androgen receptors (ARs). Certain drugs like nilutamide and cyproterone acetate retain antiandrogenic activity against specific AR mutations, offering therapeutic options.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The molecular mechanisms underlying resistance to secondary antiandrogen therapy in prostate cancer with mutant androgen receptors (ARs) require further investigation.
  • Understanding these mechanisms is crucial for developing effective treatment strategies.

Purpose of the Study:

  • To investigate the effects of various antiandrogens on wild-type and mutant ARs.
  • To elucidate the structural basis for the efficacy of certain antiandrogens against specific AR mutations.

Main Methods:

  • Assessed the transcriptional activity of wild-type and mutant (W741C, T877A, W741C+T877A) ARs in response to antiandrogens.
  • Utilized molecular modeling, including crystal structure analysis and docking studies with the MOE package.

Main Results:

  • Bicalutamide and hydroxyflutamide suppressed T877A and W741C mutant AR activity, respectively.
  • Nilutamide and cyproterone acetate inhibited W741C and double mutants, with structural analysis suggesting retained antiandrogenic properties.
  • The W741C mutation disrupts hydrophobic interactions essential for AR agonist conversion.

Conclusions:

  • Switching to different antiandrogens could be a viable strategy for managing prostate cancer with mutant ARs.
  • Nilutamide and cyproterone acetate show potential for treating patients with specific AR mutations like W741C.

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