IACS-010759 (1570496-34-2) is a potent (IC50 = 1.1 nM isolated mouse complex I) and selective inhibitor of complex I of the mitochondrial electron transport chain (OXPHOS). IACS-010759 displayed in vivo efficacy in glycolysis-deficient glioblastoma and AML models without cytotoxicity to normal cells. The lack of cytotoxicity to normal cells, as opposed to other complex I inhibitors, is attributed to its unique binding location on complex I.2 Complex I inhibition by IACS-010759 causes an ROS-induced decrease in the endogenous PP2A inhibitor CIP2A leading to cell death.3 It has also displayed potential in various chemotherapy-resistant cancer cell lines.4-7
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