Accession Number : AD1048731


Title :   Multivalent Peptidomimetic Conjugates as Inhibitors of Androgen Receptor Function in Therapy-Resistant Prostate Cancer


Descriptive Note : Technical Report,30 Sep 2016,29 Sep 2017


Corporate Author : New York University New York United States


Personal Author(s) : Kirshenbaum, Kent


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1048731.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 8


Abstract : Androgens are hormones that play a critical role in stimulating prostate cancer growth. Androgens activate a protein called the androgen receptor (AR), which regulates genes involved in cell growth. Although powerful anti-androgen drugs can be administered to block AR action and have been used successfully to treat patients with prostate cancer, over time the tumors become resistant to the drugs, leaving few treatment options. The goal of this proposal is to develop a new approach to block AR activity and stop prostate cancer growth using a new family of molecules called multivalent peptidomimetic conjugates. To accomplish our goals, we will create a set of conjugates with anti-androgens linked to the peptidomimetic backbone at variable intervals along the molecular chain. We will test these molecules for their ability to bind to AR. Those that bind tightly will then be tested in tumor models to evaluate if they block androgen-dependent prostate cancer cell growth. To understand how these molecules block AR function, we will determine the three-dimensional structure of AR bound to the peptidomimetic conjugates. These studies will be used to guide our ability to tailor the conjugates for optimal interactions with the AR.


Descriptors :   androgens , prostate cancer , proteins , peptides , inhibitors , assays , pharmacokinetics , Xray crystallography


Subject Categories : Medicine and Medical Research
      Biochemistry
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE