UAMC-4821

UAMC-4821, a lipophilic radical-trapping antioxidant (RTA) and potent, orally bioavailable ferroptosis inhibitor, is designed to surpass the limitations of ferrostatin-1 and UAMC-3203. Demonstrating high potency (IC50 = 5.20 nM in HT-1080 cells, with FENIX assay confirming RTA activity), UAMC 4821 exhibits excellent oral bioavailability (63% in mice), low clearance, and high brain concentrations (123 ng/g after 24h, IV 10 mg/kg in mice), indicating superior ADME properties and blood-brain barrier penetration over earlier ferrostatins. Functionally, UAMC4821 directly neutralizes lipid peroxyl radicals within phospholipid bilayers, preventing membrane damage and ferroptotic death, thereby enhancing its attractiveness for CNS-targeted explorations.