Small molecule inhibitors targeting the "achilles' heel" of androgen receptor activity

Cancer Res. 2011 Feb 15;71(4):1208-13. doi: 10.1158/0008-5472.CAN_10-3398. Epub 2011 Feb 1.


Androgen ablation therapy remains the gold standard for the treatment of advanced prostate cancer, but unfortunately, it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer (CRPC). Mounting evidence supports the concept that development of CRPC is causally related to continued transactivation of androgen receptor (AR). All current therapies that target the AR are dependent on the presence of its C-terminal ligand-binding domain (LBD). However, it is the N-terminal domain (NTD) of the AR that is the "Achilles' heel" of AR activity, with AF-1 being essential for AR activity regardless of androgen. Recent efforts to develop drugs to the AR NTD have yielded EPI-001, a small molecule, sintokamide peptides, and decoys to the AR NTD with EPI-001, the best characterized and most promising for clinical development based upon specificity, low toxicity, and cytoreductive antitumor activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Androgen Receptor Antagonists / isolation & purification*
  • Androgen Receptor Antagonists / pharmacology
  • Androgen Receptor Antagonists / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / surgery
  • Humans
  • Male
  • Models, Biological
  • Molecular Targeted Therapy / methods*
  • Orchiectomy
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / surgery
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Small Molecule Libraries / analysis
  • Treatment Failure


  • Androgen Receptor Antagonists
  • Receptors, Androgen
  • Small Molecule Libraries