2. Academic Validation
  3. Formoterol, a clinically approved drug, inhibits ferroptosis by suppressing lipid peroxidation and attenuates APAP-induced acute liver injury

Formoterol, a clinically approved drug, inhibits ferroptosis by suppressing lipid peroxidation and attenuates APAP-induced acute liver injury

  • Chem Biol Interact. 2025 Sep 4:421:111724. doi: 10.1016/j.cbi.2025.111724.
Lin-Song Teng 1,  Zhen-Dong Ying 2,  Xiao-Han Sun 3,  Hao-Cheng Hou 4,  Shi-Dong Qiu 5,  Peng Liu 6,  Ke-Jing Li 3,  Lei Zhang 7,  Xie-Huang Sheng 8
Affiliations

Affiliations

  • 1 College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, 250014, China; Second Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250001, China.
  • 2 Second Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250001, China.
  • 3 College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, 250014, China.
  • 4 The First Clinical College, Shandong University, Jinan, 250014, China.
  • 5 School of Pharmaceutical Sciences, Shandong First Medical University (Institute of Materia Medica), Jinan, 250117, China.
  • 6 Guangxi Tianming Pharmaceutical Co., Ltd., Hechi, 547000, China.
  • 7 Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Tissue Engineering Laboratory, Department of Radiology, Shandong First Medical University, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, 250014, China. Electronic address: qygkzl1818@163.com.
  • 8 College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, 250014, China. Electronic address: shengxiehuang@sdnu.edu.cn.
PMID: 40914538 DOI: 10.1016/j.cbi.2025.111724
Abstract

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 β2-adrenergic agonist widely used to treat asthma and COPD, as a potent and selective Ferroptosis inhibitor through scaffold-based screening of FDA-approved drugs. Formoterol confers robust protection against ferroptotic cell death induced by diverse triggers across multiple human and rodent cell lines, functioning independently of classical pathways such as GPX4, FSP1, or iron chelation. Mechanistic studies reveal that formoterol suppresses Ferroptosis by directly scavenging lipid peroxyl radicals, mediated by its unique ortho-amino phenol moiety. In vivo, formoterol significantly alleviates acetaminophen-induced acute liver injury, reducing hepatic lipid peroxidation and preserving tissue integrity. These findings establish formoterol as a clinically approved agent with previously unrecognized anti-ferroptotic activity, offering a compelling example of drug repurposing to accelerate the development of ferroptosis-targeted therapies.

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