Synthesis and Evaluation of Novel RSK Inhibitors in a Living Human Breast Model
Abstract
RSK (p90 Ribosomal S6 kinase) is critical for breast cancer proliferation and thus a promising target for therapeutic intervention. A highly specific inhibitor of RSK, called SL0101, was previously discovered but found to possess poor biological stability and potency. The purpose of this project is to identify a drug for breast cancer based on SL0101 that works by inhibiting RSK, by designing and chemically synthesizing analogues of SL0101 that improve on its biological stability and potency and ultimately evaluating them in a living human breast tissue model for anticancer activity. The major findings have been the discovery of analogues of Sl0101 that are more potent and more biologically stable thab Sl0101 and the solution ofand X-Ray crystal structure of SL0101 in complex with RSK2. These discoveries represent significant steps toward the goal of identifying an analogue of SL0101 that could be used as a drug for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- AD1002963
Entities
People
- Michael Hilinski