Zharp1-163 is a dual inhibitor of ferroptosis and necroptosis, effectively blocks ferroptosis by reducing reactive oxygen species (ROS) levels and inhibits necroptosis by potently and selectively targeting RIPK1 kinase (IC50=406.1 nM).
Zharp1-163 significantly inhibits erastin- or RSL3-induced ferroptosis in HT-1080 cells with EC50 of 0.95 uM and 1.33 uM respectively.
Zharp1-163 blocks TNF-α-induced necroptosis in HT-29 cells with EC50 of 0.1 uM, also efficiently inhibits TNF-mediated necroptosis, with EC50 values of approximately 0.11 μM in MEFs and 0.08 μM in mouse fibroblast L929 cells.
Zharp1-163 inhibits apoptosis induced by TNFα plus Smac mimetic in MEFs, does not affect pyroptosis in THP-1 cells.
Zharp1-163 suppresses lipid ROS peroxidation to inhibit ferroptosis.
Zharp1-163 blocks the cellular activation of RIPK1, RIPK3 and MLKL upon necroptotic stimulation.
Zharp1-163 selective and strongly inhibits RIPK1 kinase activity with IC50 of 406.1 nM.
Zharp1-163 (5 mg/kg, i.p.) ameliorates TNF-α-induced systemic inflammatory response syndrome in mouse model of TNF-induced SIRS.