SOD1 inhibitor ATN-224

An orally bioavailable, second-generation tetrathiomolybdate analog with potnetial antiangiogenic and antineoplastic activities. SOD1 inhibitor ATN-224 selectively chelates the copper ion in copper-zinc superoxide dismutase 1 (SOD1), inhibiting SOD1 activity; this may result in a decrease in intra-cellular H2O2 levels and, in turn, increased activity of intracellular phosphatases. The ATN-224-mediated increase in phosphatase activity may interfere with the activation of multiple kinase signaling pathways required for cellular proliferation and angiogenesis. This agent has been shown to inhibit VEGF and FGF-2 signaling in endothelial cells, IGF-1, EGF, NF-kB, and integrin signaling in tumor cells, and PDGF signaling in pericytes.