Degradation and Transcriptional Inhibition of HIF-2alpha Protein by 17-AAG
Description of Invention:
The technology is directed to the use of 17-allylaminogeldanamycin (17-AAG) and, by analogy, other geldanamycin derivatives to inhibit the activity of hypoxia inducible factor-2alpha (HIF-2alpha). HIF-2alpha is thought to play an important role in tumor growth in the lung and endothelium, and is overexpressed in a majority of renal carcinomas. Accordingly, the technology suggests the use of 17-AAG and other geldanamycin derivatives to reduce levels of HIF-2alpha in cells that overexpress the protein, for example to treat cancer. According to the lead inventor, HIF-2alpha plays a central role behind the mechanism of action of geldanamycin in renal cancer. The inventors also predict that certain geldanamycin derivatives will have therapeutic benefit in tumors overexpressing HIF-2alpha, and that those derivatives could also find therapeutic utility in clinical conditions involving hypervascularization.
Inventors:
Jennifer Isaacs (NCI) Leonard Neckers (NCI)
Related Technologies:
DHHS Reference No. E-169-2003/0-US-01 filed 03 Oct 2003 (U.S. Provisional Patent Application No. 60/508,752) - "Geldanamycin Derivatives with Methyl Substituted Hydrogen Atom at the N22 Position as Anti-Cancer Agents" (Lee et al.)
Portfolios: Cancer
Cancer -Therapeutics-Biological Response Modifiers Cancer -Therapeutics
For Additional Information Please Contact: Adaku Nwachukwu J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301 435-5560
Email: madua@mail.nih.gov
Fax: 301 402-0220
