Inhibitors of Fatty Acid Synthase for Prostate Cancer
Annual rept. 1 May 2011-30 Apr 2012
WAKE FOREST COLL WINSTON-SALEM NC
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The purpose of this proposal was to develop and optimize chemical scaffolds as potential inhibitors of fatty acid synthase FASN, specifically the thioesterase TE domain. This line of investigation was based on a series of observation by many groups, including ours, that FASN represents a valuable drug target. It isoverexpressed in prostate cancer and appears to be required for tumor cells to survive. Through an iterative scheme of in silico design, activity-based screening and structural analyses we identified a series of novel pharmacophores with the ability to inhibit the thioesterase domain of FASN. This proposal had three specific aims. They were 1 To optimize compounds through structure-based design, chemical syntheses and in vitro testing, 2 To determine the toxicological and pharmacokinetic properties of the most promising analogs, and 3 To test the efficacy of the analogs in mouse xenograft models of human prostate cancer. Here we summarize the findings by our group during the course of the research proposal.
- Anatomy and Physiology
- Medicine and Medical Research