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.


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


Licensing Contact:
Betty Tong , Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325
Rockville , MD 20852
Email: tongb@mail.nih.gov
Phone: 301-594-6565
Fax: 301-402-0220

OTT Reference No: E-220-2011/0

Updated: 07/05/2013