Nitric oxide (NO) has a broad spectrum of actions in physiological and pathological processes. NO-donor drugs have shown therapeutic effect in several cancer types by inducing apoptosis but the concentrations required have suggested limited clinical applicability. For cancers such as non-small cell lung cancer where most therapies are not curative, there remains a need for effective treatments.
Scientists at the National Cancer Institute have identified a diazeniumdiolate-based NO releasing prodrug, JS-36-25, with selective cytotoxicity towards cancer cells. This prodrug has potent tumoristatic activity in lung cancer cells in vitro and in mice xenografts. Treatment with JS-36-25 in vivo led to 85% reduction of tumor growth. The tumoristatic potency of the compound had a negative correlation with the level of endogenous reactive oxygen species (ROS) in the cancer cells. Thus, in addition to potent tumoristatic activity when administered alone, this compound is predicted to have a strong synergy with therapeutics that act through generation of ROS, such as bortezomib, doxorubicin, as well as high-energy radiation.
- Could be used as a stand-alone therapy or in combination with currently available therapeutics
- Potent tumoristatic activity with selective cytotoxicity for cancer cells over normal cells
- Demonstrated 85% reduction of tumor growth in vivo
- Predicted synergy with other therapeutics
Maciag A, et al. The nitric oxide prodrug JS-K is effective against non-small-cell lung cancer cells in vitro and in vivo: involvement of reactive oxygen species. [PMID: 20962031]
Maciag A, et al. Activation of the c-Jun N-terminal kinase/activating transcription factor 3 (ATF3) pathway characterizes effective arylated diazeniumdiolate-based nitric oxide-releasing anticancer prodrugs. [PMID: 22003962]
Nandurdikar R, et al. Structural modifications modulate stability of glutathione-activated arylated diazeniumdiolate prodrugs. [PMID: 22480849]
- U.S. Provisional: U.S. Provisional Patent Application Number 13/509,431, Filed 01 Jun 2012
- Foreign Filed: Australia - Patent Application 2010319398, Filed 09 May 2012
- Foreign Filed: Canada - Patent Application 2780633, Filed 10 May 2012
- Foreign Filed: Europe - Patent Application 10778814.3, Filed 14 May 2012