ZZW-115 is a potent NUPR1 inhibitor with a Kd of 2.1 μM. ZZW-115 is a derivative of Trifluoperazine (TFP). ZZW-115 shows a dose-dependent tumor regression with no neurological side effects and induces cell death mainly by necroptosis and apoptosis[1] [2].

ZZW-115 (0.1-33 μM; 72 hours) effectively kills cancer cells, with an IC 50 in the range of 0.84 μM (ANOR) to 4.93 μM (HN14) [1]. ZZW-115 (0-100 μM; 24-72 hours) is efficient to kill these tumor cells with an IC 50 in the range of 0.42 μM (Hep2G cells) to 7.75 μM (SaOS-2 cells) [1]. ZZW-115 induces pancreatic cell death by necrosis and apoptosis. ZZW-115 treatment induces a decrease in ATP production and induces a ROS overproduction [1]. LDH release is significantly higher in ZZW-115-treated cells (MiaPaCa-2, 02-063, LIPC, Foie8b, and HN14 cells) than in control cells in a concentration-dependent manner. Similarly, caspase 3/7 activity is also greater in ZZW-115-treated cells. These experiments demonstrated that ZZW-115 exerted both pronecrotic and proapoptotic effects [1]. Cell Viability Assay [1] Cell Line: ANOR cells, MiaPaCa-2, 02-063, 01008, LIPC, 02136, HN01,01046, AOIPC, Foie8b, HN14 cells Concentration: 0.1- 33 μM Incubation Time: 72 hours Result: Was efficient in killing cancer cells, with an IC 50 in the range of 0.84 μM (ANOR) to 4.93 μM (HN14). Cell Proliferation Assay [1] Cell Line: U87, A375, U2OS, SaOS-2, HT29, SK-CO-1, LS174T, H1299 and H358, HepG2, PC3, THP-1, Daudi, Jurkat and MDA-MB-231 cells Concentration: 0-100 μM Incubation Time: 24 or 72 hours Result: Was efficient to kill these tumor cells with an IC 50 in the range of 0.42 μM (Hep2G cells) to 7.75 μM (SaOS-2 cells).

ZZW-115 (0.5-5 mg/kg; injection; daily for 30 days) inhibits the pancreatic xenografted tumors growth [1]. ZZW-115 (5 mg/kg for 30 days; immunocompetent C57BL/6 mice were orthotopically implanted with Panc02 cells) treatment shows the tumor size is almost unmeasurable in some cases [1]. Animal Model: NMRI-Foxn1nu/Foxn1nu mice (nude mice) xenografted with MiaPaCa-2 cells [1] Dosage: 5, 2.5, 1.0, or 0.5 mg/kg Administration: Injection, daily for 30 days Result: When the mice were injected with 5 mg/kg ZZW-115, the tumors stopped growing a few days after treatment and their size decreased progressively, almost disappearing at the end of the treatment.