Necrocide 1

Necrocide 1, a necrosis by sodium overload (NECSO) inducer, is a selective transient receptor potential melastatin 4 (TRPM4) agonist with an EC₅₀ of 306.3 nM for human TRPM4. Necrocide 1 triggers TRPM4-dependent necrotic cell death through the induction of sodium influx. Necrocide 1 induces hallmarks of immunogenic cell death incurring calreticulin (CALR) exposure, ATP secretion and high mobility group box 1 (HMGB1) release. Necrocide 1 can be used for the study of breast and prostate cancer^[1][2][3]. In Vitro:Necrocide 1 (compound (S)-38) (72 h)shows antiproliferative activity with an IC₅₀ value of 0.48 and 2 nM for MCF-7 and PC3, respectively^[1].
Necrocide 1 (100 μM, 4-24 h) can induce phosphorylation of eIF2α in MCF-7 and A2780 cells^[1].
Necrocide 1 (0.1-1000 nM, 24 h) induces necrotic cell death in various human cancer cell lines (MCF7, MB468) with species specificity, showing no effect on mouse cells due to TRPM4 differences^[2].
Necrocide 1 (50-100 nM, 1-6 h) triggers massive Na⁺ influx, K⁺ efflux, membrane depolarization, and cell edema in MCF7 cells, which is blocked by TRPM4 knockout or sodium depletion^[2].
Necrocide 1 (200-1000 nM, 16 h) shows increased cytotoxicity in Cos7 cells expressing gain-of-function TRPM4 mutants linked to cardiac arrhythmias, compared to wild-type TRPM4^[2].
Necrocide 1 (1 μM, 0.5-1 h) specifically activates human TRPM4 (EC₅₀ ≈ 306.3 nM) but not mouse TRPM4, as shown by patch-clamp and CETSA assays^[2].
Necrocide 1 (100 nM, 3 h)-induced necrosis is inhibited by Clotrimazole (HY-10882) and dihydropyridines in MCF7 cells, blocking Na⁺ influx^[2].
Necrocide 1 (50 nM, 4 h) induces reactive oxygen species (ROS) production in MCF-7 cells^[3].
Necrocide 1 (25-100 nM, 12-48 h)-induced cell death is not inhibited by necroptosis inhibitors, ferroptosis inhibitors, pyroptosis inhibitor, or PARP inhibitor in MCF-7 and MDA-MB-468 cells^[3].
Necrocide 1 (0.05-1 μM, 48 h) induces calreticulin (CALR) exposure, ATP secretion, and HMGB1 release, which are inhibited by CsA and NecroX-5 (HY-104015) in MCF-7 cells^[3].
In Vivo:Necrocide 1 (compound (S)-38) (20 mg/kg, i.v., on days 0 and 7) exhibits potent antitumor efficacy in PC3 rat xenograft model^[1].
Necrocide 1 (40 mg/kg, i.v., on day 0, with a second injection on day 28) induces significant and sustained tumor regression in PC-3 xenografts in nude mice (effect lasting up to 20 days)^[3].
Necrocide 1 (100 mg/kg, i.g., 3 times/week, 2 weeks) reduces tumor growth in PC-3 xenografts in athymic mice^[3].
Necrocide 1 (30 mg/kg, i.v., 3 times/week, 2 weeks) suppresses tumor growth in MCF-7 xenografts in athymic mice^[3].