Stroke is the third leading cause of death in the U.S., affecting at least 500,000 patients annually, and is considered the most common cause of adult disability. Pharmacological intervention has made little, if any, impact on preventing neurological damage once a stroke has occurred. Reactive oxygen species (ROS), which mediate tissue damage in numerous pathologies, have been implicated in the neurological damage resulting from stroke. Eukarion has developed a class of synthetic molecules that are catalytic ROS scavengers, mimicking the endogenous antioxidant enzymes SOD and catalase. One of these compounds, EUK-134, is highly protective in a rodent model for stroke, even when administered three hours after the onset of brain ischemia. This project will investigate the potential therapeutic value of these compounds for stroke.
The specific aims are: (1) To characterize the catalytic and chemical properties of the compounds, focusing on those to be tested in vivo; (2) To further characterize the efficacy of EUK-134 with respect to their effectiveness in the stroke model. The overall goal of this Phase I project is to select candidate(s) for future preclinical and clinical development as therapeutic agents for stroke.
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Doctrow, Susan R; Lopez, Argelia; Schock, Ashley M et al. (2013) A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin. J Invest Dermatol 133:1088-96 |
Rosenthal, Rosalind A; Fish, Brian; Hill, Richard P et al. (2011) Salen Mn complexes mitigate radiation injury in normal tissues. Anticancer Agents Med Chem 11:359-72 |
Liesa, Marc; Luptak, Ivan; Qin, Fuzhong et al. (2011) Mitochondrial transporter ATP binding cassette mitochondrial erythroid is a novel gene required for cardiac recovery after ischemia/reperfusion. Circulation 124:806-13 |
Doctrow, Susan R; Huffman, Karl; Marcus, Catherine Bucay et al. (2002) Salen-manganese complexes as catalytic scavengers of hydrogen peroxide and cytoprotective agents: structure-activity relationship studies. J Med Chem 45:4549-58 |