Inhibitors of Nitric Oxide Synthase for Treatment of Melanoma

Selective Neuronal Nitric Oxide Synthase Inhibitors for the Treatment of Human Melanoma NU 2010-163 Inventors Haitao Mark Ji Frank L Meyskens, Jr. Thomas L. Poulos Richard B. Silverman Fengtian Xue Sun Yang A pharmaceutical composition that provides melanoma protection Abstract UV radiation exposure, especially sunburn at a young age, is commonly linked to melanoma incidence. As an important environmental carcinogen, UV radiation not only generates reactive oxygen species but also produces a large amount of nitric oxide (NO) in human skin. Upon NO stress by the NO donor DETA, both melanoma proliferation and invasion potential are both significantly stimulated. Northwestern researchers have identified a neural NO synthase (nNOS) that demonstrates an important role in generating NO and mediating NO stress in human melanoma. They have studied the effects on nNOS in vitro cell culture and in vivo human biopsy studies. More interestingly, they discovered that an induction of nNOS was evident with UVB radiation and basic fibroblast growth factor (bFGF) incubation. Conversely, knockdown of nNOS with siRNA efficiently reduced the DETA-induced melanoma proliferation and invasion potential. A novel synthesized nNOS inhibitor, JI-11, has been identified to inhibit nNOS activity. Results show that co-treatment with JI-11 significantly attenuated the alterations induced by UVB radiation and DETA treatments. These studies represent an innovative and promising strategy for melanoma prevention. Applications o Diagnosis of melanoma proliferation o Strategy for melanoma prevention. Advantages o New means of diagnosis o Potential melanoma prophylactic IP Status US application filed Marketing Contact Allan Nader, PhD Invention Manager (e) a-nader@northwestern.edu (p) 847.491.4456