Androgen receptor antagonists: a patent review (2008-2011)

Expert Opin Ther Pat. 2012 May;22(5):541-65. doi: 10.1517/13543776.2012.682571.


Introduction: Androgen receptor (AR) antagonists are predominantly used as chemical castration to treat prostate cancer (i.e., in conjunction with androgen deprivation therapy (ADT)). Unfortunately, castration-resistant prostate cancer (CRPC) typically develops that is refractory to targeted therapy. Insights into CRPC biology have led to the emergence of a promising clinical candidate MDV3100 (1) and a resurgence in this field. A pipeline of preclinical competitive (C-terminally directed) antagonists was discovered using a variety of innovative screening paradigms. Some inhibit nuclear translocation, selectively downregulate or degrade AR (SARD), antagonize wild-type and escape mutant AR (pan-antagonists) and/or antagonize AR target organs in vivo. Separately, the N-terminal domain has emerged as a promising novel target for noncompetitive antagonists.

Areas covered: AR antagonists whose patents published between 2008 and 2011 are reviewed. Antagonists are organized based on the screening paradigm reported as discussed above.

Expert opinion: Novel mechanisms provide a more informed basis for selecting a competitive antagonist; however, high potency and favorable in vivo properties remain paramount. Noncompetitive antagonists have theoretical advantages suggestive of improved clinical efficacy, but no clinical proof of concept as of yet.

Publication types

  • Review

MeSH terms

  • Androgen Receptor Antagonists / chemistry
  • Androgen Receptor Antagonists / pharmacology*
  • Animals
  • Antineoplastic Agents, Hormonal / chemistry
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Drug Design
  • Drug Resistance, Neoplasm
  • Humans
  • Legislation, Drug
  • Male
  • Molecular Structure
  • Mutation
  • Patents as Topic
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Transport
  • Receptors, Androgen / drug effects*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Structure-Activity Relationship


  • AR protein, human
  • Androgen Receptor Antagonists
  • Antineoplastic Agents, Hormonal
  • Receptors, Androgen