Ferroptosis-IN-21

Ferroptosis-IN-21 is a ferroptosis inhibitor that protects against renal I/R injury by suppressing ferroptosis and directly scavenging peroxyl radicals. Ferroptosis-IN-21 displays broad-spectrum anti-ferroptotic efficacy across multiple inducers in renal tubular epithelial cells, with nanomolar potency and robust suppression of lipid Reactive Oxygen Species (ROS). Ferroptosis-IN-21 significantly ameliorates renal I/R injury in mice, reducing histological damage, functional impairment, and inflammatory cytokine expression, while decreasing lipid peroxidation biomarkers such as 4-hydroxynonenal. Ferroptosis-IN-12 can be used for research in the field of ferroptosis-targeted drug development^[1]. In Vitro:Ferroptosis-IN-21 (compound 6) (0.01-10 μM, 24 h) exhibits nanomolar cytoprotective activity (EC₅₀ = 61.7 nM) and completely reverses cell death at 200 nM in HT-1080 cells, and dose-dependently protects Human Kidney Cortex epithelial cells (HKC) and Human Kidney 2 (HK-2) cells from ferroptosis induced by RSL-3 (HY-100218A) and FIN-56, confirming its broad-spectrum efficacy^[1].
Ferroptosis-IN-21 (50-500 nM, 24 h) significantly suppresses RSL-3-induced lipid ROS accumulation and MDA elevation, and has no effect on GPX4 protein levels^[1].
Ferroptosis-IN-21 (10 µM) does not chelate iron ions, ruling out an iron-chelating mechanism^[1].
Ferroptosis-IN-21 (1-80 µM, 30 min) exhibits potent direct radical scavenging activity in Cell-free DPPH assay^[1]. In Vivo:Ferroptosis-IN-21 (5 and 10 mg/kg, i.p., 24 hours and 1 hour pre-treatment) shows potent renoprotective effects against ischemic acute kidney injury (AKI) in a renal ischemia-reperfusion mice model^[1].