Development of a second-generation antiandrogen for treatment of advanced prostate cancer Academic Article uri icon


MeSH Major

  • Androgen Antagonists
  • Antineoplastic Agents
  • Phenylthiohydantoin
  • Prostatic Neoplasms


  • Metastatic prostate cancer is treated with drugs that antagonize androgen action, but most patients progress to a more aggressive form of the disease called castration-resistant prostate cancer, driven by elevated expression of the androgen receptor. Here we characterize the diarylthiohydantoins RD162 and MDV3100, two compounds optimized from a screen for nonsteroidal antiandrogens that retain activity in the setting of increased androgen receptor expression. Both compounds bind to the androgen receptor with greater relative affinity than the clinically used antiandrogen bicalutamide, reduce the efficiency of its nuclear translocation, and impair both DNA binding to androgen response elements and recruitment of coactivators. RD162 and MDV3100 are orally available and induce tumor regression in mouse models of castration-resistant human prostate cancer. Of the first 30 patients treated with MDV3100 in a Phase I/II clinical trial, 13 of 30 (43%) showed sustained declines (by >50%) in serum concentrations of prostate-specific antigen, a biomarker of prostate cancer. These compounds thus appear to be promising candidates for treatment of advanced prostate cancer.

publication date

  • May 8, 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2981508

Digital Object Identifier (DOI)

  • 10.1126/science.1168175

PubMed ID

  • 19359544

Additional Document Info

start page

  • 787

end page

  • 90


  • 324


  • 5928