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:||
||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)
US Application No. 61/549,862
PCT Application No. PCT/US2012/060785
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 firstname.lastname@example.org. To view the NCI collaborative opportunity announcement, click here.
Betty Tong , Ph.D.
NIH Office of Technology Transfer
OTT Reference No: E-220-2011/0