Compounds that Interfere with the Androgen Receptor Complex
Investigators at the National Institutes of Health (NIH) have discovered compounds that have potential as novel anti-androgen therapeutics. The immunophilin protein FKBP52 is part of a protein complex that helps fold the androgen receptor (AR) protein, a target for treating prostate cancer, and enhances its activity. Disruption of the FKPB52-AR interaction greatly reduces the activity of the AR. With the goal of finding potential therapeutic compounds that inhibit the FKBP52-mediated activation of AR, several small molecules were tested and found to be antagonists of FKBP52 and to inhibit AR activity in prostate cells. These compounds can serve as therapeutics for the treatment of prostate cancer and benign prostate enlargement. Moreover, FKBP52 is also implicated in the regulation of other hormone receptors so these compounds could be used to treat other hormone-dependent diseases such as diabetes or even used as contraceptives.
One of the standard treatments for prostate cancer makes use of anti-androgens, like bicalutamide, which compete for binding with the natural male hormones to AR and inhibit their proliferative activity. The problem with available anti-androgen drugs is that prostate tumors eventually become drug resistant resulting in so-called androgen-resistant prostate cancer. One cause of this is an increase in the levels of AR produced by the prostate cancer cells. A solution to this problem may lie in disrupting the protein folding of AR by interfering with its interaction with FKBP52 using these compounds.
The Center for Cancer Research, Urologic Oncology Branch, seeks parties to co-develop, or license antagonists of FKBP52-dependent remodeling of the androgen receptor.
Potential Commercial Applications: | Competitive Advantages: |
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Development Stage:
Pre-clinical (in vivo)
Related Invention(s):
E-065-2013
Inventors:
Leonard Neckers (NCI) ➽ more inventions...
Marc Cox () ➽ more inventions...
Intellectual Property:
U.S. Pat: 8859207 issued 2014-10-14
Publications:
De Leon JT et al Proceedings of the National Academy of Sciences 108(29), 11878-83 (2011)
Cheung-Flynn et al. 15831525
Collaboration Opportunity:
Licensing and research collaboration
Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515
OTT Reference No: E-162-2009
Updated: Aug 17, 2020