Elesclomol | Copper chelator/Cuproptosis inducer

Elesclomol (488832-69-5) induced oxidative stress in cancer cells via rapid generation of reactive oxygen species.¹ It preferentially binds copper ions outside the cell and selectively transports inside the mitochondria with subsequent reactive oxygen species generation leading to apoptosis.^2,3 Elesclomol can restore copper homeostasis in models of copper deficiency and disorders of copper metabolism.^4,5 Copper-induced cell death (Cuproptosis) caused by Elesclomol is now believed to occur via direct binding of copper to lipoylated components of the tricarboxylic acid cycle causing protein aggregation and subsequent iron-sulfur protein loss leading to proteotoxic stress and cell death.⁶

References/Citations:

1. Kirshner et al. (2008), Elesclomol induces cancer cell apoptosis through oxidative stress; Mol. Cancer Ther. 7 2319
2. Blackman et al. (2012), Mitochondrial electron transport is the cellular target of the oncology drug elesclomol; PLoS One 7 e29798
3. Nagai et al. (2012), The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells; Free Radic. Biol. Med. 52 2142
4. Soma et al. (2018), Elesclomol restores mitochondrial function in genetic models of copper deficiency; Proc. Natl. Acad. Sci. USA 115 8161
5. Guthrie et al. (2020), Elesclomol Alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice; Science 368 620
6. Tsvetkov et al. (2022), Copper induces cell death by targeting lipoylated TCA cycle proteins; Science 375 1254