Pharmaceutical compositions which inhibit FKBP52-mediated regulation of androgen receptor function and methods of using same
Patent Number: US8859207
Executive Summary:
General Description:
The present invention reports the pharmaceutical composition, methods of use of compounds called FK506 Binding Protein 52 (FKBP52)-targeting agents or FTAs. FKBP52 regulates androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR) by potentiating their receptor-mediated signal transduction pathways. The FTAs recognize FKBP52 binding domain on the androgen receptor and inhibit FKBP52 from binding to it. Hence, FTAs could modulate steroid-receptor functions. Because of these properties, the inventors claim that the FTAs could be employed for the treatment of diseases associated with deregulated androgenic, glucocorticoid and/or progesterone activity such as benign prostatic hyperplasia (BPH), insulin independent diabetes, diminished male or female fertility and prostate cancer.
Weaknesses:
Patent Status:
Publications:
Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11878-83. doi: 10.1073/pnas.1105160108. Epub 2011 Jul 5. PMID: 21730179
Inventor Bio: Leonard M. Neckers
https://ccr.cancer.gov/urologic-oncology-branch/leonard-m-neckers
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Active (granted)
- Patent Link: https://patents.google.com/patent/US8859207/
- Research Institute: National Cancer Institute and University of Texas at EI Paso
- Disease Focus: Prostate cancer and hormone-related medical conditions
- Basis of Invention: FK-506 binding protein 52 (FKBP52) binding to receptor hormone binding domain modulates by potentiating the activity of steroid hormone receptors such as androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR)
- How it works: Compounds FKBP52-targeting agents (FTAs) inhibit FKBP52-receptor enhancing activity by binding to the AR, GR, PR and modulate their activity without competing with hormone binding
- Lead Challenge Inventor: Leonard M. Neckers
- Inventors: Leonard M. Neckers, Marc B. Cox, Jane B. Neckers, Yeong Sang Kim, Aki Iwai, Yangmin Ning, Johanny Tonos de Leon, Heather Balsiger
- Novelty:
- Compounds downregulating or upregulating steroid hormone activity
- Compounds targeting AR, GR and PR without affecting hormone binding
- Clinical Applications:
- Hormone related diseases with decreased or increased steroid receptor activity
General Description:
The present invention reports the pharmaceutical composition, methods of use of compounds called FK506 Binding Protein 52 (FKBP52)-targeting agents or FTAs. FKBP52 regulates androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR) by potentiating their receptor-mediated signal transduction pathways. The FTAs recognize FKBP52 binding domain on the androgen receptor and inhibit FKBP52 from binding to it. Hence, FTAs could modulate steroid-receptor functions. Because of these properties, the inventors claim that the FTAs could be employed for the treatment of diseases associated with deregulated androgenic, glucocorticoid and/or progesterone activity such as benign prostatic hyperplasia (BPH), insulin independent diabetes, diminished male or female fertility and prostate cancer.
Weaknesses:
- Very limited preclinical data
Patent Status:
- Priority date: 2009-09-15
- Filing date: 2012-11-08
- Publication date: 2014-10-14
- Grant date: 2014-10-14
Publications:
Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11878-83. doi: 10.1073/pnas.1105160108. Epub 2011 Jul 5. PMID: 21730179
Inventor Bio: Leonard M. Neckers
https://ccr.cancer.gov/urologic-oncology-branch/leonard-m-neckers
