Accession Number : ADA496320


Title :   Development of the C-Terminal Inhibitors of Heat Shock Protein 90 in the Treatment of Prostate Cancer


Descriptive Note : Final rept. 15 Sep 2005-14 Sep 2008


Corporate Author : KANSAS UNIV MEDICAL CENTER RESEARCH INST KANSAS CITY


Personal Author(s) : Holzbeierlein, Jeffrey


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a496320.pdf


Report Date : Oct 2008


Pagination or Media Count : 26


Abstract : To develop and evaluate novel compounds which inhibit the C-terminal portion of Hsp90 in prostate cancer models. To develop a library of novobiocin analogues to be tested in vitro initially and then in a mouse model. Major findings: we have tested over 220 analogues of the original parent compound (A-1) all of which have been tested in at least two commonly used prostate cancer cell lines LNCaP and PC3. Screening has been evaluated by both Western Blot of client proteins which include the androgen receptor, Akt, Hsp90, and HER2, and MTT assay. Furthermore, with our most effective compounds we have examined the mechanism of action and have examined cell cycle data. We have evaluated one compound in vivo and are currently evaluating our newest most promising compound in vivo in an orthotopic mouse model.


Descriptors :   *PROSTATE CANCER , INHIBITORS , ANDROGENS , PROTEINS , CELLS(BIOLOGY)


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE