Accession Number:

ADA604653

Title:

Targeting Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Prostate Cancer

Descriptive Note:

Annual rept. 30 Sep 2012-29 Sep 2013

Corporate Author:

TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER

Personal Author(s):

Report Date:

2013-10-01

Pagination or Media Count:

19.0

Abstract:

We have made significant progress in our work with peptidomimetics targeting ligand-dependent and ligand-independent androgen receptor signaling in prostate Cancer. We have designed, created, tested and validated 23 analogues of our lead compound and have identified chemistries that are optimal for peptidomimetic stability, potency and selectivity. Towards this end, we first established a highly efficient synthetic protocol to generate these compounds. From our testing we identified several compounds with promising activities that are currently under investigation for in-depth analysis and that will help refine the next generation of more potent peptidomimetics. We have further refined our genomic signaling assays to reflect what is currently known about AR-driven signaling in prostate cancer and have shown that the peptidomimetics block both ligand-dependent and ligand-independent androgen receptor signaling. Importantly, we have shown that these peptidomimetics are orally bioavailable and biologically active. Finally, we have published several manuscripts, including one in Nature Communications on our lead D2 compound and its remarkable functional activity in prostate cancer cell lines. In the coming year, we intend to build on our accomplishments and further develop the peptidomimetics as biologically usable compounds.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE