ATN-224 + temozolomide

ATN-224 + temozolomide is an investigational combination therapy consisting of two small molecules: ATN-224, a second-generation choline salt of tetrathiomolybdate which acts primarily as a copper chelator and inhibits superoxide dismutase 1 (SOD1), and temozolomide, an oral alkylating agent approved for use in treating malignant gliomas and melanomas. ATN-224 inhibits angiogenesis and ROS scavenging through copper depletion and SOD1 inhibition, leading to increased oxidative stress in cancer cells and suppression of tumor angiogenesis[3][8]. Temozolomide causes DNA alkylation and subsequent tumor cell death, especially in cells with impaired DNA repair. The combination has been shown to have additive cytotoxic effects, particularly in melanoma and glioma models[1][4]. This strategy targets both tumor cell survival and adaptation to oxidative stress, and the combination is being studied as a potential therapy primarily in cancer indications where increased ROS and angiogenesis are key tumorigenic mechanisms[1][2][4].