@article {618391,
	title = {Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in Glioblastoma-Patient-Derived Cells},
	journal = {Cell Chem Biol},
	volume = {25},
	number = {5},
	year = {2018},
	month = {2018 May 17},
	pages = {585-594.e7},
	abstract = {Transition metals are essential, but deregulation of their metabolism causes toxicity. Here, we report that the compound NSC319726 binds copper to induce oxidative stress and arrest glioblastoma-patient-derived cells at picomolar concentrations. Pharmacogenomic analysis suggested that NSC319726 and 65 other structural analogs exhibit lethality through metal binding. Although NSC319726 has been reported to function as a zinc ionophore, we~report here that this compound binds to copper~to~arrest cell growth. We generated and validated pharmacogenomic predictions: copper toxicity was substantially inhibited by hypoxia, through an hypoxia-inducible-factor-1α-dependent pathway; copper-bound NSC319726 induced the generation of reactive oxygen species and depletion of deoxyribosyl purines, resulting in cell-cycle arrest. These results suggest that metal-induced DNA damage may be a consequence of exposure to some xenobiotics, therapeutic agents, as well as other causes of copper dysregulation, and reveal a potent mechanism for targeting glioblastomas.},
	issn = {2451-9448},
	doi = {10.1016/j.chembiol.2018.02.010},
	author = {Shimada, Kenichi and Reznik, Eduard and Stokes, Michael E and Krishnamoorthy, Lakshmi and Bos, Pieter H and Song, Yuyu and Quartararo, Christine E and Pagano, Nen C and Carpizo, Darren R and deCarvalho, Ana C and Lo, Donald C and Stockwell, Brent R.}
}
