Table 1 Potential therapeutic drugs targeting ferroptosis for PF.

From: Emerging roles of ferroptosis in pulmonary fibrosis: current perspectives, opportunities and challenges

Therapeutic agents	Targeting molecule	Potential Mechanism	Application	Ref.
DFO	Iron chelator	Inhibit fenton reaction and mitochondrial ROS production	Attenuate pulmonary epithelial cell death and fibrosis induced by cigarette smoke	[25]
DFP	Iron chelator	Inhibit fenton reaction and iron-containing lipid oxygenases	Attenuate PF in transfusion-dependent patients with thalassemia major	[153]
CQ	Iron chelator	Inhibit fenton reaction and alleviate inflammatory responses	Attenuates PF induced by BLM and PQ	[108]
Ciclopirox	Iron chelator	Inhibit fenton reaction	Attenuate cystic fibrosis lung infections	[155]
Rosiglitazone	ACSL4 inhibitor	Upregulate PTEN and decrease TGF-β	Attenuate PF induced by PQ and BLM	[157, 158]
pioglitazone	ACSL4 inhibitor	Activate PPAR-γ to remedy fatty acid oxidation	Attenuate cardiac fibrosis	[159]
Troglitazone	ACSL4 inhibitor	Inhibit synthesis of TGF-β and fibroblast proliferation and differentiation	Attenuate peritoneal fibrosis and PF	[161, 162]
Empagliflozin	SGLT2 inhibitor	Inhibit ferroptosis via Sesn2/AMPK/Nrf2/HO-1 pathway	Attenuate PF	[164]
Sepiapterin	RTA	Increase BH4 levels in plasma	Attenuate PF induced by BLM	[132]
Ferrtatin-1	RTA	Inhibit lipid peroxidation	Attenuate silicosis fibrosis	[167]
Liproxstatin-1	RTA	Inhibit lipid peroxidation	Attenuate RILF	[182]
Se-Met	Selenium supplement	Inhibit cGAS/STING/NF-κB pathway.	Attenuate lung epithelial cells senescence	[174]
Ebselen	Selenium supplement	Decrease oxidized DAG	Attenuates PF induced by BLM	[175]
Allosteric GPX4 activators	GPX4 agonist	Enhance the acticity of GPX4	Unkown	[177]
NAC	GSH precursor	Increase pulmonary GSH levels	Attenuate PF induced by BLM	[178, 179]
β-mercaptoethanol	Reductant	Promote system xc^- uptake of cysteine	Suppresse human lung fibroblast proliferation	[183]
Sulforaphane	Nrf-2 agonist	Decrease 4-HNE levels	Attenuate PF induced by BLM	[127]
DHQ	flavonoid	Inhibit ferritin autophagy	Attenuate Silicosis	[27]
Fraxetin	NCOA4	Form stable binding with NCOA4 and reduces ferritin autophagy	Attenuate PF induced by BLM	[150]
Baicalein	Arachidonic Acid inhibitor	Inhibit GPX4 degradation	Attenuate PF	[185,186,187,188]
Zileuton	LOX inhibitor	Inhibit LOXs induced lipid peroxidation	Attenuate IPF	[189]
Ficolin B	Unkown	Promote ferroptosis through the cGAS/STING signaling pathway	Attenuate PF induced by BLM	[113]
Dihydroartemisinin	Unkown	Regulate the Nrf2/HO-1 pathway to mitigate cellular ferroptosis	Attenuate radiation-induced lung injury and PF	[115]
Tripterygium wilfordii Hook.f.	Unkown	Mitigate oxidative stress and ferroptosis through the Nrf2/HO-1 pathway	Attenuate paraquat-induced lung injury and fibrosis	[116]
ELA-32	mTOR agonist	Activate APJ-Akt-mtor-P70S6K signaling	Attenuate myocardial fibrosis	[190]
Liraglutide	Unkown	Elevate the expression of SLC7A11 and the Nrf2/HO-1/GPX4 signaling pathway	Attenuate liver fibrosis	[192]
Roxadustat (FG-4592)	HIF inhibitor	Inhibit ferroptosis via Akt/GSK-3β/Nrf2 Pathway	Attenuate kidney fibrosis induced by folic acid	[193]
Zinc protoporphyrin	HO-1 inhibitor	Inhibit HO-1 mediated mitochondrial dysfunction	Attenuate PF induced by PM2.5	[28]

RTA radicals trap antioxidants, PF Pulmonary fibrosis, RILF Radiation-induced lung fibrosis, BLM Bleomycin, DFO Defetoxamine, DFP Deferiprone, CQ Chloroquine, PQ Paraquat, ACSL4 Long chain acyl-CoA synthetase 4, PTEN Phosphatase and tensin homolog, TGF-β Transforming Growth Factor-β, PPAR-γ proliferator-activated receptor γ, DAG diacylglycerol, Se-Met Selenomethionine, LOX lipoxygenase, IPF Idiopathic pulmonary fibrosis. GPX4 Glutathione peroxidase 4, Nrf-2 Nuclear factor erythroid 2-related factor 2, 4-HNE 4-Hydroxy-2-nonenal, NAC N-acetylcysteine, GSH Glutathione, ELA-32 Elabela −32, mTOR mechanistic target of rapamycin, HIF Hypoxia-inducible factor, GSK-3β Glycogen synthase kinase-3, HO-1 Heme oxygenase-1, PM2.5 particulate matter 2.5, NCOA4 Nuclear receptor coactivator 4, RIPK receptor interacting protein kinase, SIRT1 Sirtuin-1, SLC7A11 Solute carrier family 7 membrane 11.

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Table 1 Potential therapeutic drugs targeting ferroptosis for PF.

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