Elesclomol

Elesclomol (STA-4783) is a potent copper ionophore and promotes copper-dependent cell death (cuproptosis). Elesclomol specifically binds ferredoxin 1 (FDX1) α2/α3 helices and β5 strand. Elesclomol inhibits FDX1-mediated Fe-S cluster biosynthesis. Elesclomol is an oxidative stress inducer that induces cancer cell apoptosis. Elesclomol is a reactive oxygen species (ROS) inducer. Elesclomol can be used for Menkes and associated disorders of hereditary copper deficiency research^[1][2][3][4]. 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^[1].
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^[1].
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^[2].
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^[3].
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^[5].
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%^[4].
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^[4].