Disruption of the Interaction of the Androgen Receptor with Chromatin: A Novel Therapeutic Approach in Prostate Cancer

Abstract

We have made significant progress in our work with small molecules including peptides/peptidomimetics to disrupt the interaction between androgen receptor and critical coregulators, such as the pioneering transcription factor FOXA1 on the DNA. We have shown that the interface between AR-FOXA1 plays important roles in AR responsiveness and activity. We have designed, synthesized, and tested a panel of peptides/peptidomimetics to disrupt the interaction between AR andFOXA1. The effects of these candidate compounds have been tested in multiple assays and various prostate cancer cell lines. We have further utilized and refined the potent and sensitive NanoBit in vivo complementation assay to evaluate other possible reagents through high throughput screening strategy. We are now in the process of comparing and confirming these lead compounds in prostate cancer models. In the coming year, we intend to further optimize these compounds and complete the proposed mechanistic studies.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2016
Accession Number
AD1034536

Entities

People

  • Lu Miao

Organizations

  • University of Texas Southwestern Medical Center

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Androgen Receptors
  • Androgens
  • Biomedical Research
  • Cell Line
  • Cells
  • Chromosome Structures
  • Department Of Defense
  • Molecules
  • Neoplasms
  • Professional Development
  • Prostate
  • Prostate Cancer
  • Protein-Protein Interactions
  • Proteins
  • Small Molecules

Fields of Study

  • Chemistry

Readers

  • Oncology (Cancer Research).
  • Oncology and Biomarker-Based Cancer Detection.
  • Prostate Cancer Biology.