Potent (IC 50 = 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...
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Potent (IC 50 = 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. Complex I inhibition by IACS-010759 causes an ROS-induced decrease in the endogenous PP2A inhibitor CIP2A leading to cell death. It has also displayed potential in various chemotherapy-resistant cancer cell lines
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