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.

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