Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells

Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11878-83. doi: 10.1073/pnas.1105160108. Epub 2011 Jul 5.


Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR regulatory mechanisms are promising alternatives for the treatment of castrate-resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an important positive regulator of AR in cellular and whole animal models and represents an attractive target for the treatment of prostate cancer. We used a modified receptor-mediated reporter assay in yeast to screen a diversified natural compound library for inhibitors of FKBP52-enhanced AR function. The lead compound, termed MJC13, inhibits AR function by preventing hormone-dependent dissociation of the Hsp90-FKBP52-AR complex, which results in less hormone-bound receptor in the nucleus. Assays in early and late stage human prostate cancer cells demonstrated that MJC13 inhibits AR-dependent gene expression and androgen-stimulated prostate cancer cell proliferation.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Discovery
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescence
  • Gene Expression Regulation / drug effects*
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Male
  • Mice
  • Models, Molecular*
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Multiprotein Complexes / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / metabolism*
  • Tacrolimus Binding Proteins / antagonists & inhibitors*
  • Tacrolimus Binding Proteins / metabolism
  • Yeasts
  • beta-Galactosidase


  • HSP90 Heat-Shock Proteins
  • Multiprotein Complexes
  • Receptors, Androgen
  • beta-Galactosidase
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 4