Zharp1-163

Zharp1-163 is a dual inhibitor of ferroptosis and necroptosis. It effectively blocks ferroptosis by reducing reactive oxygen species (ROS) levels and inhibits necroptosis by potently and selectively targeting RIPK1 kinase activity (KD = 240 nM; IC50 = 406.1 nM). Zharp1-163 suppresses the cellular activation of RIPK1, RIPK3, and MLKL induced by necroptosis stimuli. The compound significantly alleviates TNF-α-induced systemic inflammatory syndrome, preventing TNF-α-induced lethality and hypothermia in mice. Additionally, Zharp1-163 mitigates acute kidney injury related to necroptosis and ferroptosis in models induced by cisplatin and ischemia-reperfusion. Zharp1-163 is applicable for studying diseases linked to cellular death pathways, such as kidney diseases.