In Vitro: Elesclomol (STA-4783) binds the FDX1 α2/α3 helices and β5 strand, but does not bind the paralog protein FDX2. Elesclomol-Cu(II) is an FDX1 neo-substrate. FDX1 protein binds and reduces the elesclomol-Cu(II) complex. Elesclomol-Cu (1:1 ratio) (40 nM) for only 2 hours results in a 15- to 60-fold increase in intracellular copper levels that triggered cell death more than 24 hours later in ABC1 cells. The addition of copper to elesclomol at a 1:1 molar ratio prior to treatment significantly reduces cell viability when cells are grown in glycolytic (glucose media) conditions. Elesclomol (200 nM; 18 hours) treatment increases the number of early and late apoptotic cells in HSB2 cells. Elesclomol induces apoptosis in cancer cells through the induction of oxidative stress. Elesclomol significantly inhibits the cell viability of SK-MEL-5, MCF-7, and HL-60 cells with IC50 values of 110 nM, 24 nM and 9 nM, respectively.
In Vivo: Elesclomol (10 mg/kg; subcutaneous injection; every three days from post-natal day 5 to 26 and once weekly until post-natal day 54) treatment ameliorates severe cardiac pathology with a partial reduction in hypertrophy. Cardiac [Cu] increased with Elesclomol treatment from a vehicle knockout level of 34 to 55%. Elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Elesclomol prevents detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse.