Formoterol, a Clinically Approved Drug, Inhibits Ferroptosis by Suppressing Lipid Peroxidation and Attenuates APAP-Induced Acute Liver Injury.

Ferroptosis is an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation and implicated in various human diseases. Despite intensive research, clinically applicable ferroptosis inhibitors remain unavailable. In this study, we identify formoterol, a β-adrenergic agonist widely used to treat asthma and COPD, as a potent and selective ferroptosis inhibitor through scaffold-based screening of FDA-approved drugs.

Discovery of 8-hydroxy-tetrahydroquinoline ferroptosis inhibitors for the treatment of acute kidney injury.

Acute kidney injury (AKI) is a severe public health challenge, characterized by high incidence and mortality rates, alongside a lack of effective therapeutic interventions. Emerging evidence highlights kidney tubular ferroptosis as a key driver of AKI pathogenesis. While α-tocopherol, a natural lipid antioxidant, exhibits potent anti-ferroptotic activity, its therapeutic potential remains limited by a lack of structural optimization.

3-hydroxyanthranilic acid analog mitigates ischemia-reperfusion injury by inhibiting cardiomyocyte ferroptosis through the activation of Nrf2/HO-1/GPX4.

Myocardial ischemia-reperfusion injury (MIRI) is a widespread condition that causes cardiac dysfunction, myocardial cell loss, and fibrosis. It is associated with substantial global morbidity, disability, and mortality, placing a considerable strain on healthcare systems and economies. 3-Hydroxyanthranilic acid (3-HA), an endogenous intermediates of tryptophan metabolism, exhibits modest anti-ferroptotic effects; however, its limited efficacy hinders its clinical applicability.

Discovery of Novel -Aminophenol Derivatives Targeting Lipid Peroxidation with Potent Antiferroptotic Activities.

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of -aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these -aminophenol derivatives exhibit unique intra-H bond interactions, compelling -amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity.