ZZW-115

ZZW-115 is a potent NUPR1 inhibitor with IC50s of 0.42 μM in Hep2G cells and 7.75 μM in SaOS-2 cells. ZZW-115 shows evident antitumor activity through its interaction with NUPR1.

ZZW-115 is capable of efficiently killing the pancreatic tumor cell lines by targeting NUPR1 and inhibits the growth of other tumor-derived cells. ZZW-115 induced cell death is the consequence of a decrease of ATP production by the mitochondria accompanied by an increase of mitochondrial ROS production with a transient metabolic shift toward anaerobic glycolysis inhibiting.^[1]

Cells are plated in 96-well plates. Twenty-four hours later, the media are supplemented with 0–100 μM concentration of ZZW-115, and are incubated for another additional 24 or 72 hours. Cell viability is estimated after addition of the CellTiter-Blue viability reagent (Promega) for 3 hours according to the protocol provided by the supplier. Cell viability the concernings normalized with respect to untreated cell rates.

ZZW-115 can disrupt tumor growth at low doses and can reduce tumor size for the xenografted tumors, without obvious neurological side effects in the mice. ZZW-115 is a very efficient anticancer drug candidate in vivo on mice because, due mainly to necrosis, it is capable not only of stopping tumor growth but also of decreasing the tumor size until its disappearance.^[1]