ZZW-115 is a potent NUPR1 inhibitor with a Kd of 2.1 μM and is a derivative of Trifluoperazine (TFP). It shows dose-dependent tumor regression without neurological side effects and induces cell death mainly by necroptosis and apoptosis[1] [2].

ZZW-115, at concentrations ranging from 0.1 to 100 μM and incubation periods between 24 and 72 hours, demonstrates significant anticancer efficacy by effectively killing a variety of cancer cells. It exhibits IC50 values from as low as 0.42 μM in Hep2G cells to 7.75 μM in SaOS-2 cells, indicating its potency across different cell lines including ANOR, HN14, and others [1]. Moreover, ZZW-115 prompts cancer cell death through both necrosis and apoptosis mechanisms, highlighted by increased lactate dehydrogenase (LDH) release and caspase 3/7 activity in treated cells compared to controls. This is further supported by a decrease in ATP production and an overproduction of reactive oxygen species (ROS), showcasing its dual pro-necrotic and pro-apoptotic actions [1].

Administering ZZW-115 via injection at doses ranging from 0.5 to 5 mg/kg daily for 30 days inhibited growth in pancreatic xenografted tumors in NMRI-Foxn1nu/Foxn1nu (nude) mice implanted with MiaPaCa-2 cells. At a dosage of 5 mg/kg, ZZW-115 treatment in immunocompetent C57BL/6 mice orthotopically implanted with Panc02 cells resulted in a significant reduction of tumor size, rendering it almost unmeasurable in some instances. Notably, tumors ceased to grow a few days post-administration of 5 mg/kg ZZW-115 and exhibited a progressive decrease in size, nearing complete disappearance by the treatment's conclusion.