Inhibitors for Androgen Receptor Activation Surfaces

Abstract

Our research demonstrated a new protein interaction site on the androgen receptor. We showed that the site called BF3 has the characteristics of functioning in repression and likely binds one or more proteins. We are presently performing experiments to identify these proteins. We used X-ray crystallography to learn the binding mode of small molecule compounds that bind to this site. The BF3 site is allosteric because binding is accompanied by weakening the interaction of the androgen receptor with coactivators. X-ray crystallography demonstrated disorder of coactivator peptides that were well ordered before adding the compounds. Our studies suggest that compounds may be designed to target this site and weaken activity of the androgen receptor. Such compounds could form a new class of chemical therapeutics for treatment of prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2008
Accession Number
ADA496399

Entities

People

  • Robert J. Fletterick

Organizations

  • University of California, San Francisco

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Androgen Receptors
  • Androgens
  • Chemical Compounds
  • Chemistry
  • Crystallography
  • Crystals
  • Diseases And Disorders
  • Hormones
  • Inhibitors
  • Molecules
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Proteins
  • X Rays
  • X-Ray Crystallography

Fields of Study

  • Chemistry

Readers

  • Neuroscience
  • Powder metallurgy of Titanium alloys.
  • Prostate Cancer Biology.