Molecular Profiling of EPI-001: An Inhibitor of Androgen Receptor Signaling With a Disputed Mechanism of Action
Abstract
The goals of this project are to synthesize alkyne-functionalized EPI-001 analogues and to determine their protein binding partners in prostate cancer cell lines. The anticipated outcome is the annotation of the activity-associated protein targets of EPI-001 that will be valuable in future drug development efforts. The progress achieved during this 1-year award include: (1) synthesizing a set of alkyne-tagged EPI-001 probes, (2) elucidating appropriate concentrations and incubation times for dosing probes to LNCaP cells to afford probe-protein adducts, (3) optimizing protocols for the isolation of probe-protein adducts over monomeric avid in resin and demonstrating protein-binding by SDS-PAGE, and (4) identifying the proteins captured by the EPI-001 analogues by LC-MS/MS. Ongoing studies are focused on performing quantitative proteomics with the prepared EPI-001 analogues to elucidate changes in protein levels following compound dosage. Additional control experiments and appropriate replicate experiments required for scientific publication are also being performed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1030622
Entities
People
- Daniel A Harki
Organizations
- University of Minnesota