Targeting Prostate Cancer with Bifunctional Modulators of the Androgen Receptor

Abstract

The overall goal of this research project is to develop and implement a conceptually innovative strategy for extrinsic regulation of the androgen receptor (AR) to target the transcriptional misregulation mediated by this receptor in prostate cancer. This strategy utilizes bifunctional molecules that simultaneously interact with AR and with components of the chromatin remodeling machinery. In the second year of funding, a paper outlining the early stages of the study was accepted for publication. Additionally, thorough characterization of HDAC inhibitor-based structures revealed that localizing HDACs to promoters via AR leads is not efficacious. However, targeting an epigenetic reader, Brd4, lead to robust and reliable extrinsic control of full-length nuclear receptor function. In the final year of funding, this latter model will be fully extended in the prostate cancer system.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2013
Accession Number
ADA596408

Entities

People

  • Anna K. Mapp

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Bile
  • Cell Physiological Processes
  • Chemical Synthesis
  • Chemistry
  • Disease Attributes
  • Enzyme Inhibitors
  • Health Services
  • Molecules
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Public Health
  • Small Molecules
  • Therapy
  • United States

Fields of Study

  • Biology

Readers

  • Oncology
  • Prostate Cancer Biology.
  • Systems Analysis and Design