Poly ADP-Ribose Polymerase Inhibitor/ Nitric Oxide Donor Dual Prodrugs as Anti-cancer Agents


Scientists at NIH have developed a hybrid prodrug molecule with enhanced biological activity as an anti-cancer agent. Novel cancer therapeutic strategies are in high demand. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising anticancer agents. Poly (ADP-ribose) polymerase (PARP) inhibitors have also emerged as another promising class of therapeutic compounds for cancer. The two-component prodrug is expected to simultaneously deliver DNA damaging agent (NO release) with an inhibitor of DNA repair (PARP inhibitor) to a cancer cell. The prodrugs are activated by glutathione/glutathione S-transferase (GSH/GST) and release cytotoxic NO and a PARP inhibitor in the target cancer cell. The high levels of GSH/GST are often a feature of cancer cells. The compound is predicted to have strong synergy with other anticancer therapeutics.

Potential Commercial Applications: Competitive Advantages:
  • Cancer therapeutics
  • Cancer therapeutics in combination with other anticancer therapies
  Combination of DNA damaging agent and DNA repair inhibitor in one molecule has advantage over individual drug treatments.


Related Inventoion(s):
E-093-1996/3
E-025-2010/0


Inventors:
Joseph Saavedra (NCI)
Larry Keefer (NCI)
Xinhua Ji (NCI)
Anna Maciag (NCI)
Vandana Kumari (NCI)


Intellectual Property:
US Application No. 61/549,862
PCT Application No. PCT/US2012/060785

Collaboration Opportunity:

The National Cancer Institute, Chemical Biology Laboratory, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize PARP inhibitor and NO-donor hybrid prodrugs for the treatment of cancer. For collaboration opportunities, please contact John Hewes, Ph.D. at john.hewes@nih.gov. To view the NCI collaborative opportunity announcement, click here.


Licensing Contact:
Betty Tong , Ph.D.
NIH Office of Technology Transfer
Email: tongb@mail.nih.gov
Phone: 301-594-6565

OTT Reference No: E-220-2011/0

Updated: Jul-05-2013