Elesclomol  (Synonyms: STA-4783)

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].

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

400.52

Solid

C₁₉H₂₀N₄O₂S₂

488832-69-5

S=C(C1=CC=CC=C1)N(NC(CC(NN(C(C2=CC=CC=C2)=S)C)=O)=O)C

Room temperature in continental US; may vary elsewhere.

• [1]. Peter Tsvetkov, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022 Mar 18;375(6586):1254-1261.  [Content Brief]

  [2]. Peter Tsvetkov, et al. Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 2019 Jul;15(7):681-689.  [Content Brief]

  [3]. Kirshner JR, et al. Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther. 2008 Aug;7(8):2319-27.  [Content Brief]

  [4]. Liam M Guthrie, et al. Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice. Science. 2020 May 8;368(6491):620-625.  [Content Brief]

  [5]. Bair JS, et al. Chemistry and biology of deoxynyboquinone, a potent inducer of cancer cell death. J Am Chem Soc. 2010 Apr 21;132(15):5469-7  [Content Brief]