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Necrocide 1 (NC1) is an activator of transient receptor potential melastatin 4 (TRPM4).1 It induces sodium influx in HEK293 cells expressing human TRPM4 at 10 µM. NC1 increases mitochondrial membrane permeability and reactive oxygen species (ROS) levels and induces necrosis in MCF-7 breast cancer cells.2 It reduces the proliferation of various cancer cell lines (IC50s = 1.57-1000 nM) but not non-cancerous cell lines (IC50s = >10,000 nM for all). NC1 induces intratumoral necrosis and decreases tumor volume in PC3 prostate cancer and MCF-7 mouse xenograft models.
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1. Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload. Nat. Commun. 17(1), 7939 (2026).
2. Necrocide 1 mediates necrotic cell death and immunogenic response in human cancer cells. Cell Death Dis. 14(4), 238 (2023).