New data on Synta Pharmaceuticals' elesclomol presented at the AACR-NCI-EORTC Conference

Synta PharmaceuticalsNov 18 2009

Synta Pharmaceuticals Corp. (NASDAQ: SNTA), a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to treat severe medical conditions, today presented new data on the mechanism of action of elesclomol, a first-in-class oxidative stress inducer, at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics in Boston, Mass.

“Elesclomol has been shown previously to induce apoptosis in cancer cells by increasing the level of reactive oxygen species (ROS),” said Vojo Vukovic M.D., Ph.D., Chief Medical Officer, Synta Pharmaceuticals. “The results presented today provide new details on the underlying mechanism by which elesclomol elevates oxidative stress. Elesclomol binds copper in plasma, facilitates its uptake into cells, and enables a transition between copper oxidation states once inside the cell. These results also point towards the origin of elesclomol’s unusual cancer-cell selectivity – its ability to kill cancer cells with little to no effect on normal cells. Cancer cells and normal cells are well known to have distinct metabolic properties, including the electrochemical properties of the mitochondria where many of these redox reactions take place. Taking advantage of these metabolic and electrochemical differences represents an entirely new and exciting approach, distinct from kinase inhibition or conventional chemotherapy, to selectively target and kill cancer cells. These unique properties of elesclomol are important considerations for future clinical applications. Additional results related to the elesclomol mechanism of action and hematologic applications will be presented at the American Society of Hematology meeting next month.”

The results of the in vitro studies demonstrated that:

• Elesclomol binds to copper as Cu(II) outside the cell
• The chelation of copper facilitates the entry of elesclomol into the cell
• Once in the cell, elesclomol promotes a reduction reaction where Cu(II) transitions to Cu(I)
• The redox reaction leads to the generation of reactive oxygen species (ROS)
• This process is necessary for elesclomol’s anticancer activity (ability to induce oxidative stress to the point of apoptosis).