Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms (Tsvetkov et al., 2022). The mechanism of cuproptosis (copper-dependent death), is significantly different from other known cell death such as apoptosis, pyroptosis, necrosis and ferroptosis. Copper-dependent death occurs by means of direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle. This results in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, which leads to proteotoxic stress and ultimately cell death (Tsvetkov et al., 2022). Nowadays, cuproptosis has been associated with diseases such as amyotrophic lateral sclerosis (ALS), breast cancer, melanoma, adult neuroblastoma, and prostate cancer.

TargetMol’s Cuproptosis Compound Library is a collection of 400 compounds related to copper-dependent death that can be used to study its mechanism and related diseases.

Reference:Tsvetkov, P., Coy, S., Petrova, B., Dreishpoon, M., Verma, A., Abdusamad, M., Rossen, J., Joesch-Cohen, L., Humeidi, R., Spangler, R. D., Eaton, J. K., Frenkel, E., Kocak, M., Corsello, S. M., Lutsenko, S., Kanarek, N., Santagata, S., & Golub, T. R. (2022). Copper induces cell death by targeting lipoylated TCA cycle proteins. Science (New York, N.Y.), 375(6586), 1254-1261. https://doi.org/10.1126/science.abf0529