Diacylglycerol Compounds Useful as Protein Kinase C Activators and Apoptosis Inducers
Description of Invention:
This invention discloses new diacylglycerol (DAG) compounds that may be useful as chemotherapeutic agents. DAG activates many of the isozymes in the Protein Kinase C (PKC) family, a phospholipid-dependent serine/threonine-specific kinase that plays an important role in cellular growth and differentiation. The activation of PKC by DAG is important in mediating the actions of a variety of hormones, neurotransmitters, and other biological control factors. This new class of DAG compounds is proving to be superior at inducing apoptosis in androgen-sensitive LNCaP prostate cancer cells by specifically activating the alpha isozyme. The compounds are believed to receive their superior properties from the replacement of the ester oxygen with a nitrogen attached to a hydroxyl group (N-OH). The presence of the hydroxamate functionality endows the molecule with improved solubility properties making these compounds the most potent and least lipophilic DAG analogues known to date.
Inventors:
Victor E. Marquez (NCI) Peter M. Blumberg (NCI) Jeewoo Lee (NCI) Marcelo Kazanietz
Patent Status:
DHHS Reference No. E-088-01/0 filed 06 Aug 2001
Portfolios: Cancer
Cancer -Therapeutics-Biological Response Modifiers Cancer -Therapeutics
For Additional Information Please Contact: John Stansberry Ph.D.
NIH Office of Technology Transfer
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-5236
Email: stansbej@mail.nih.gov
Fax: (301) 402-0220
