Description of Invention:
Recently, a new strategy for the treatment of cancer was validated by the FDA approval of a small molecule proteasome inhibitor. This treatment strategy, while being efficacious, achieved this result by generally inhibiting all proteasome activity. However, the ubiquitin-mediated process that instructs the proteasome to degrade specific proteins is exquisitely specific to the type of protein degraded. The exact mechanism of how the individual components of the ubiquitin-mediated process regulate the amount of a specific protein present in a cell is just beginning to be elucidated with certainty. Drugs specific to these components can regulate cellular level of important proteins.
This invention is a family of 7-nitro-5-deazaflavin compounds that inhibit MDM2 protein activity in a cell. The MDM2 protein is an E3 ubiquitin ligase that mediates the transfer of ubiquitin to the important tumor suppressor protein p53: p53 will initiate apoptosis in cancer cells. By minimizing ubiquitin transfer to p53 – and its subsequent degradation – the 7-nitro-5-deazaflavin compounds can potentially increase the tumor suppressor properties of p53 by maintaining a higher concentration of the important tumor suppressor protein within the cell.
This invention could be an important next generation proteasome inhibitor as it can potentially inhibit the degradation of specific proteasome substrates.
Inventors:
Alan Weissman et al. (NCI)
Patent Status:
DHHS Reference No. E-231-2002/0 --
U.S. Provisional Application No. 60/447,610 filed 13 Feb 2003
PCT Application No. PCT/US2004/04130 filed 12 Feb 2004, which published as WO 2004/073615 on 02 Sep 2004
U.S. Patent Application No. 10/545,547 filed 12 Aug 2005
Portfolios: Cancer
Cancer -Therapeutics-Conventional Chemotherapy-Other Cancer -Therapeutics
For Additional Information Please Contact: Surekha Vathyam Ph.D.
Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/435-4076
Email: vathyams@mail.nih.gov
Fax: 301/402-0220
