IACS-010759 is a potent and selective inhibits oxidative phosphorylation with IC50 < 10 nM. It also binds to and inhibits complex I of the electron transport chain (NADH ubiquinone oxidoreductase), selectively depriving tumor cells of nutrients and energy, inhibiting nucleotide and amino acid production, and induces autophagy.

VLX600 is a novel iron-chelating inhibitor of oxidative phosphorylation, potentiated the effect of radiation in tumor spheroids in a synergistic manner. VLX600 is preferentially active against quiescent cells in colon cancer 3-D microtissues. VLX600 shows enhanced cytotoxic activity under conditions of nutrient starvation and displays tumour growth inhibition in vivo.

S-Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma.

IACS-010759 or IACS-10759 is a potent inhibitor of complex I of OXPHOS. IACS-10759 effectively inhibits ATP production and oxygen consumption in isolated mitochondria, and inhibits the conversion of NADH to NAD+ in immunoprecipitated complex I in low nM range. IACS-10759 is orally bioavailable with excellent physicochemical properties in preclinical species, and shows significant efficacy in multiple tumor indications both in vitro and in vivo. IACS-10759 causes robust tumor regression, but has no effect in the same model when glycolysis is restored.