ZZW-115 is an inhibitor of nuclear protein 1 (NUPR1).1 It binds to NUPR1 (Kd = 2.1 ?M) in a cell-free assay. ZZW-115 is cytotoxic against a panel of 11 pancreatic ductal adenocarcinoma cell lines (IC50s = 0.84-4.93 ?M), as well as against a panel of 16 additional cancer cell lines, including glioblastoma, lymphoma, and leukemia cells (IC50s =0.25-7.75 ?M). It induces apoptosis and necrosis in MiaPaCa-2, LIPC, Foie8b, 02-063, and HN14 pancreatic cancer cells when used at concentrations of 3 and 5 ?M. ZZW-115 induces accumulation of reactive oxygen species (ROS), lipid peroxidation, and ferroptosis in MiaPaCa-2 cells in a concentration-dependent manner.2 It reduces tumor growth in a MiaPaCa-2 mouse xenograft model when administered at doses of 1, 2.5, or 5 mg/kg.1
1.Santofimia-Casta?o, P., Xia, Y., Lan, W., et al.Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosisJ. Clin. Invest.129(6)2500-2513(2019) 2.Huang, C., Santofimia-Casta?o, P., Liu, X., et al.NUPR1 inhibitor ZZW-115 induces ferroptosis in a mitochondria-dependent mannerCell Death Discov.7(1)269(2021)