Accession Number : ADA570535


Title :   Inhibitors of Fatty Acid Synthase for Prostate Cancer


Descriptive Note : Annual rept. 1 May 2011-30 Apr 2012


Corporate Author : WAKE FOREST COLL WINSTON-SALEM NC


Personal Author(s) : Kridel, Steven J


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a570535.pdf


Report Date : May 2012


Pagination or Media Count : 18


Abstract : 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 analog(s), and 3) To test the efficacy of the analog(s) in mouse xenograft models of human prostate cancer. Here we summarize the findings by our group during the course of the research proposal.


Descriptors :   *PROSTATE CANCER , DRUGS , FATTY ACIDS , INHIBITORS , SYNTHASES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE