Novel Inhibitors of Protein-Protein Interaction for Prostate Cancer Therapy

Abstract

The goal of this research is to firmly establish the mechanism of androgen receptor (AR)-JunD heterodimer induction of the SSAT gene leading to oxidative stress that contributes to the development and progression of prostate cancer (PCa), and to identify small molecules that specifically inhibit this AR-JunD interaction and prevent development/progression of PCa in preclinical models. Data from this research will identify the most efficacious drug to be further developed in preclinical toxicity testing and clinical trials for PCa that fall beyond the scope of this proposal. Significant findings during Year 3 of the research include: 1) establishment of specific inhibition of AR-JunD interaction by the lead AR-JunD inhibitor compound in prostate cancer cells via immunocytochemistry analysis, 2) establishment of the maximum tolerated dose (MTD) in an oral regimen of the lead compound in mice, and 3) preliminary evidence of efficacy of the lead compound administered at MTD oral regimen against xenograft and transgenic mouse models of prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2013
Accession Number
ADA580368

Entities

People

  • George Wilding

Organizations

  • University of Wisconsin–Madison

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Biomedical Research
  • Cancer
  • Clinical Trials
  • Culture Techniques
  • Inhibitors
  • Lead Compounds
  • Molecules
  • Neoplasms
  • Oxidative Stress
  • Prostate
  • Prostate Cancer
  • Proteins
  • Small Molecules
  • Toxicity
  • Xenografts

Fields of Study

  • Biology

Readers

  • Oncology (Cancer Research).
  • Prostate Cancer Biology.