Elesclomol

Elesclomol (STA-4783) is a first-in-class investigational drug currently undergoing clinical evaluation as a novel cancer therapeutic. Elesclomol significantly inhibits the cell viability of SK-MEL-5, MCF-7 and HL-60 with IC50 of 110 nM, 24 nM and 9 nM, respectively. Elesclomol induces oxidative stress by provoking a buildup of reactive oxygen species within cancer cells. Elesclomol interacts with the electron transport chain (ETC) to generate high levels of ROS within the organelle and consequently cell death. Elesclomol induces apoptosis in cancer cells through the induction of oxidative stress. Treatment of cancer cells in vitro with elesclomol resulted in the rapid generation of reactive oxygen species (ROS) and the induction of a transcriptional gene profile characteristic of an oxidative stress response. In addition, N-acetylcysteine blocked drug-induced apoptosis, indicating that ROS generation is the primary mechanism responsible for the proapoptotic activity of elesclomol.