Targeting Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Prostate Cancer
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA604653
Entities
People
- Ganesh V Raj
Organizations
- University of Texas at Dallas