liproxstatin-1 / Jilin University - LARVOL DELTA

Nrf2 de-SUMOylation alleviates myocardial ischemia-reperfusion injury (MIRI) by attenuating myocardial ferroptosis in mice. (PubMed, Redox Rep) - "Ferroptosis inhibitor liproxstatin-1 (Lip-1) was used to demonstrate ferroptosis participation in Nrf2 de-SUMOylation regulated MIRI. In vitro, SUMO1/sentrin-specific protease 1 Senp1 KO H9C2 cells were subjected to RSL3-induced ferroptosis to explore underlying mechanism...Mechanistically, Nrf2 de-SUMOylation was associated with a reduction in Transferrin receptor (Tfr) expression level, thereby mitigating ferroptosis in cardiomyocytes. This study highlighted the role of Nrf2 SUMOylation in promoting ferroptosis during MIRI and identified Nrf2 de-SUMOylation as a potential therapeutic target for MIRI."

Journal • Preclinical • Cardiovascular • Coronary Artery Disease • Heart Failure • Myocardial Ischemia • Reperfusion Injury • ANXA2

The research progress of ferroptosis in acute lung injury. (PubMed, Biochem Biophys Rep) - "Its core molecular machinery, including glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), and the cystine/glutamate antiporter system Xc-, becomes dysregulated across various ALI subtypes, such as sepsis, ischemia-reperfusion, and COVID-19.This review delineates how ferroptosis contributes to ALI through iron overload, uncontrolled lipid peroxidation, and failure of antioxidant defenses, ultimately leading to pulmonary endothelial and epithelial cell death. We further summarize subtype-specific mechanisms and evaluate emerging therapeutic strategies, including ferroptosis inhibitors (e.g., liproxstatin-1), Nrf2 activators, and iron chelators, highlighting their potential for targeted intervention in ALI/ARDS."

Journal • Review • Acute Lung Injury • Acute Respiratory Distress Syndrome • Cardiovascular • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Reperfusion Injury • Respiratory Diseases • Septic Shock • ACSL4 • GPX4

Methylmercury induces ferroptosis by suppressing GPX4 protein levels in C17.2 mouse neural stem cells. (PubMed, J Toxicol Sci) - "First, we examined the effects of various ferroptosis inhibitors (ferrostatin-1, liproxstatin-1, and deferoxamine) on methylmercury-induced cell death. C17.2 cells overexpressing FLAG-GPX4 exhibited greater resistance to methylmercury than control cells. These results indicate that methylmercury induces ferroptosis in C17.2 cells by suppressing GPX4 protein levels."

Journal • Preclinical • GPX4 • SLC7A11

Ferroptosis in heart failure: from molecular insights to therapeutic implications. (PubMed, Cardiovasc Res) - "It is an abundant form of regulated cell death in the myocardium of many heart failure animal models, including the chronic ischemic, pressure overload, diabetic, septic, obesity-related and doxorubicin-induced cardiomyopathy models...Although definitive causality between ferroptosis and heart failure has not yet been established, emerging evidence suggests that ferroptosis contributes to heart failure progression, supported by multi-layer rescue with classic inhibitors (ferrostatin-1, liproxstatin-1, iron chelators) and by cardiometabolic drugs with clinical efficacy in heart failure (Sodium-Glucose Cotransporter 2 inhibitors, sacubitril/valsartan, finerenone, levosimendan, nicorandil) as well as polyphenols, which restore systolic and/or diastolic indices and reverse remodelling...In this review, through critical synthesis of existing evidence, we analyse current literature, discuss translational barriers and propose a new conceptual mechanistic framework - "the..."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity

Role of Ferroptosis in 2, 4, 6-Trinitrobenzenesulfonic acid Induced Ulcerative Colitis: Targeting Iron Metabolism for Therapeutic Gain. (PubMed, Free Radic Res) - "Small-molecule inhibitors such as Ferrostatin-1 and Liproxstatin-1 effectively reduce mucosal damage and restore antioxidant balance, while iron chelators like deferoxamine alleviate iron overload and ROS generation. Collectively, these findings establish ferroptosis as a pivotal mechanism in TNBS-induced UC, linking oxidative stress and iron dysregulation to mucosal injury. Targeting ferroptosis offers a promising therapeutic avenue for UC management, though further clinical and translational studies are needed to validate its efficacy and safety."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • GPX4 • HMOX1

Liproxstatin-1 ameliorates cerebral ischemia-reperfusion injury through inhibiting ferroptosis. (PubMed, Int J Neurosci) - "In vitro experiments further demonstrated that liproxstatin-1 significantly enhanced cell viability and reduced Fe2+ and reactive oxygen species (ROS) levels. Liproxstatin-1 inhibits the process of ferroptosis and alleviates CIRI in rats."

Journal • Cardiovascular • Ischemic stroke • Metabolic Disorders • Reperfusion Injury • ACSL4 • FTH1 • GPX4 • IL17A • TFRC

Limitations of Ferroptosis Inhibitors on the Doxorubicin-Induced Cardiotoxicity. (PubMed, Antioxidants (Basel)) - "In both H9c2 cardiomyocyte cell lines and human induced pluripotent stem cell-derived cardiomyocytes, ferrostatin-1 and liproxstatin-1 rescued cell death induced by RSL3, a ferroptosis inducer, but failed to prevent doxorubicin-induced cell death. Finally, doxorubicin-injected mice treated with ferroptosis inhibitors exhibited significantly reduced survival and increased levels of N-terminal pro B-type natriuretic peptide, a biomarker of heart failure. These findings suggest that inhibiting ferroptosis alone is insufficient to mitigate doxorubicin-induced cardiotoxicity."

Journal • Breast Cancer • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Ferroptosis-driven cryoinjury in porcine testicular tissue: Mechanisms, antioxidant-based cryoprotection, and translational strategies for fertility preservation. (PubMed, Anim Reprod Sci) - "Lipid-directed radical-trapping agents (ferrostatin-1, liproxstatin-1), vitamin-E analogs, selenium (to support GPX4 activity), and iron chelators each reduce post-thaw lipid peroxidation, preserve membrane and mitochondrial integrity, and enhance sperm/SSC performance...Finally, we outline priorities for porcine-specific ferroptosis assays, standardized antioxidant-enriched freezing protocols, dose optimization, and long-term reproductive endpoints. Collectively, the evidence supports a paradigm shift: ferroptosis is a central driver of cryodamage in porcine testicular tissue, and ferroptosis-targeted, antioxidant-based cryoprotection offers a rational path to higher SSC survival, improved graft architecture, and better translational fertility outcomes."

Journal • Preclinical • Review • GPX4

The myocardial ischemic cascade network and multi-target synergistic interventions: From molecular mechanisms to therapeutic innovations. (PubMed, Biochem Pharmacol) - "Cell death is targeted using ferroptosis inhibitors (e.g., Liproxstatin-1), NLRP3/caspase-1 blockers, and autophagy regulators (e.g., Astragaloside IV). Mitochondrial/metabolic therapies include mitochondrial-targeted drugs (e.g., CsA@PLGA-PEG-SS31), metabolic modulators (Trimetazidine), and neuroendocrine agents (ARNI, SGLT2 inhibitors)...Precision medicine integrates multi-omics and AI for risk stratification, while biomimetic nanocarriers enhance drug delivery. Future therapies should co-target the "energy-death-inflammation" network to advance myocardial ischemia treatment toward systemic repair and improved clinical outcomes."

Journal • Review • Cardiovascular • Gene Therapies • Inflammation • Metabolic Disorders • Myocardial Ischemia • Reperfusion Injury • ALDH2 • NLRP3 • SIRT3

Research Progress of Ferroptosis in Cerebral Infarction. (PubMed, Brain Behav) - "Ferroptosis represents a convergent, actionable mechanism of ischemic neuronal death and secondary brain injury. Multimodal interventions that combine lipid peroxidation control, iron homeostasis, mitochondrial protection, and inflammation resolution are biologically compelling. Key next steps include: validating real-time biomarkers for patient selection and timing; optimizing brain-penetrant delivery systems; integrating ferroptosis modulation with reperfusion therapies; and advancing rigorously designed phase II/III trials to establish efficacy and safety in defined stroke subtypes."

Journal • Review • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Metabolic Disorders • Reperfusion Injury • Vascular Neurology • ACSL4 • AIFM2 • CDKN1A • GPX4 • SLC7A11

Improved DCD Heart Transplant Function Through Ferroptosis Blockade in a Model of Experimental Normothermic Ex Vivo Perfusion. (PubMed, Transplantation) - "Normothermic EVHP combined with Lip-1 treatment can be a promising DCD heart preservation strategy, which can alleviate myocardial IRI, ameliorate endothelial dysfunction, and improve posttransplant cardiac function for DCD hearts via inhibiting myocardial ferroptosis."

IO biomarker • Journal • Preclinical • Cardiovascular • Oncology • Reperfusion Injury • Transplantation • ACSL4 • ANXA2 • BCL2 • CASP3 • CD31 • GPX4 • IL1B • IL6 • PECAM1 • SLC7A11 • TNFA

NOX4/Keap1/Nrf2/ROS Signaling Drives Ferroptosis in Trimethyltin Chloride-Induced Cardiac Developmental Malformations. (PubMed, Toxicology) - "Intervention with ferroptosis-specific inhibitors (Liproxstatin-1 and Myricetin) confirmed that ferroptosis directly contributes to TMT-induced cardiac developmental defects. This study demonstrates that TMT induces cardiac malformations by activating ferroptosis via the nox4/Keap1/Nrf2/ROS signaling axis. These findings reveal a novel mechanism underlying TMT cardiotoxicity, provide theoretical insights for assessing TMT exposure as a risk factor for congenital heart disease, and identify potential molecular targets for therapeutic intervention."

Journal • Cardiovascular • Heart Failure • GPX4 • NOX4

GPX4 Promotes Optic Nerve Regeneration and Retinal Ganglion Cell Neuroprotection. (PubMed, Mol Ther) - "To explore potential neuroprotective role of GPX4, we test AAV-mediated RGC-specific overexpression of GPX4 in these models and found that GPX4 promotes significant ON regeneration, RGC survival, and visual functional preservation. Interestingly, lipid peroxidation inhibitor liproxstatin-1, but not ferroptosis inhibitor deferiprone, presents significant RGC neuroprotection and axon regeneration, indicating the detrimental role of lipid peroxidation but not ferroptosis in optic neuropathies, and the therapeutic potential of modulating lipid peroxidation through GPX4."

Journal • Glaucoma • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • GPX4

Effect of fish scale ointment on diabetic foot ulcer by inducing ferroptosis via the nuclear factor E2-related factor 2 pathway. (PubMed, World J Diabetes) - "Fish scale ointment promotes angiogenesis and wound healing in DFU rat models by inhibiting ferroptosis, possibly through the activation of the Nrf2 pathway."

Journal • Diabetes • ANXA2 • CD31 • GPX4 • HMOX1 • PECAM1

Ferroptosis Inhibition Enhances Osteoblast Activity: The Role of Liproxstatin-1 and Coenzyme Q10. (PubMed, Int J Mol Sci) - "Erastin-induced ferroptosis significantly reduced cell viability and increased lipid peroxidation, as evidenced by BODIPY™ 581/591 C11 staining. These results highlight CoQ10 and Lip-1 as promising candidates for bone tissue engineering, as they offer protection against ferroptosis and promote osteoblast differentiation. Overall, this study emphasizes the therapeutic potential of ferroptosis modulators for bone regeneration."

Journal • ANXA2

Ferroptosis: The Pivotal Link in Cardiovascular Diseases Pathogenesis and Therapy. (PubMed, Int J Gen Med) - "Emerging evidence indicates that several drugs targeting the ferroptosis pathway including iron chelators, antioxidants, and small-molecule inhibitors such as ferrostatin-1 and liproxstatin-1, demonstrate cardioprotective effects in preclinical models. However, translational challenges remain, including context-dependent roles of regulators like p53 and AMPK, and the need for organelle-specific interventions. This review synthesizes current knowledge and proposes ferroptosis as a promising target for precision medicine in CVDs, urging further research into biomarkers and combination therapies to mitigate the global burden of cardiovascular morbidity and mortality."

Journal • Review • Cardiovascular • Inflammation • Metabolic Disorders • AMPK • GPX4

Beyond oxidative stress: Ferroptosis as a novel orchestrator in neurodegenerative disorders. (PubMed, Front Immunol) - "Several small-molecule inhibitors-including ferrostatin-1, liproxstatin-1, and iron chelators such as deferoxamine (DFO)-have demonstrated efficacy in animal models by attenuating neuronal damage and improving behavioral outcomes through the suppression of ferroptosis. This review summarizes recent advances in understanding the role of ferroptosis in neurodegenerative disease mechanisms, focusing on its contribution to pathological progression, molecular regulation, and therapeutic interventions. By integrating current findings, we aim to provide theoretical insights into novel pathogenic mechanisms and scientific guidance for the development of targeted therapies that modulate ferroptosis to slow or halt disease progression."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Huntington's Disease • Inflammation • Metabolic Disorders • Movement Disorders • Oncology • Parkinson's Disease • Vascular Neurology • GPX4

Arsenic exposure reduces testosterone synthesis partially by evoking Leydig cell ferroptosis in mouse testes. (PubMed, Environ Pollut) - "Liproxstatin-1 (Lip-1), a specific ferroptosis inhibitor, protected against As-induced testicular Leydig cell ferroptosis...Accordingly, Lip-1 pretreatment reversed As-induced reduction of testicular T synthesis. These results suggest that As exposure reduces testicular T synthesis partially by evoking Leydig cell ferroptosis in mouse testes."

Journal • Preclinical • ACSL4 • ANXA2 • GPX4 • NCOA4

Traumatic brain injury-related ferroptosis: current perspectives. (PubMed, J Mol Med (Berl)) - "Iron chelators (e.g., deferoxamine), antioxidants (e.g., ferrostatin-1, liproxstatin-1), and natural compounds (e.g., melatonin, trehalose) demonstrate neuroprotection by mitigating oxidative stress and restoring metabolic balance. Despite progress, key gaps persist in understanding ferroptosis crosstalk with apoptosis/pyroptosis, optimizing drug delivery (e.g., nanoparticle carriers), and validating biomarkers for clinical translation. Targeting ferroptosis offers a promising avenue for TBI treatment, but further research is needed to refine therapeutic specificity and integrate these strategies into clinical practice."

Journal • Review • CNS Disorders • Inflammation • Metabolic Disorders • Vascular Neurology • ACSL4 • GPX4 • TFRC

An essential link between pyrimidine synthesis and ferroptosis suppression in erythroid differentiation (ASH 2025) - "Giemsa staining of sorted erythroid precursors in the presence of the DHODHinhibitor brequinar revealed a larger proportion of less differentiated basophilic to the moredifferentiated polychromatic erythroblasts compared to vehicle control. Co-treatment with theferroptosis inhibitor liproxstatin-1 partially rescued this erythroid differentiation block resulting in alarger proportion of polychromatic erythroblasts...Our resultsdemonstrate that the differentiation of erythroid progenitors and precursors depends on thesuppression of ferroptosis. We further reveal a novel tight link between pyrimidine metabolism andferroptosis defense in erythropoiesis and uncover distinct adaptive plasticity of de novo and salvagenucleotide synthesis during erythroid differentiation, which, in the long-term, will open new avenues totreat anemia."

Anemia • Aplastic Anemia • CD34 • GPX4

Targeting metabolic vulnerabilities in Acute Myeloid Leukemia: Therapeutic potential of l-asparaginase and synergy with venetoclax (ASH 2025) - "However, L-asp–induced lipid peroxidation wasminimal, and the annexin V positive cells induced by L-asp were only modestly suppressed by theferroptosis inhibitors liproxstatin-1 and deferoxamine. Alignedwith these findings, the combination of L-asp and venetoclax demonstrated marked synergisticcytotoxicity in these cell lines.In summary, AML with low ASNS expression shows high sensitivity to L-asp, suggesting that treatmentwith L-asp is an absolute indication. Furthermore, even in glutamine-dependent AML with high ASNSexpression, combination therapy with L-asp and venetoclax represents a promising therapeutic strategy."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ANXA5 • BCL2

Vitamin K3 metabolic fate determines pro-survival or ferroptotic outcomes in multiple myeloma via UBIAD1 and reductase axis (ASH 2025) - "Ferroptosis InhibitorSpecificity: Cell death induction by vitamin K3 (78%) was significantly attenuated by the ferroptosisinhibitor Liproxstatin-1 (reduced to 32%; P<0.01), whereas apoptosis inhibitors failed to confer protection.We establish that the functional duality of vitamin K3 is governed by its metabolic processing throughUbiA prenyltransferase domain-containing protein 1 (UBIAD1) and reductase enzymes. Specifically, inMM1S myeloma cells, low-dose vitamin K3 (1 μM) is metabolized to vitamin K2 by UBIAD1, therebyaugmenting cellular antioxidant capacity and rescuing cells from RSL3-induced ferroptosis...Mechanistically, single-electron reduction generatesunstable semiquinone radicals, propagating lipid peroxidation—a hallmark of ferroptosis.Clinical validation utilizing patient-derived organoids (PDOs) established from primary myeloma cells of 8patients revealed that sensitivity to vitamin K3 correlated with low UBIAD1 expression and elevated levelsof..."

Hematological Malignancies • Multiple Myeloma • AIFM2 • GPX4 • NQO1

Repurposing of disulfiram as a novel therapeutic agent to treat crebbp-mutant diffuse large B-cell lymphoma (DLBCL) (ASH 2025) - "Alterations in mitochondrial biology and function were observed to be CREBBP-mutant-specific, with Disulfiram-induced cytotoxicity found to be completely rescued following pre-treatment with the copper chelator TTM, but not pre-treatment with apoptosis (Z-VAD-FMK) andferroptosis inhibitors (Ferrostatin-1 and Liproxstatin-1), further confirming Disulfiram-inducedCuproptosis in our models.To test Disulfiram's safety and efficacy in vivo, we performed subcutaneous injection of CREBBP wild typeand mutant cells in NSG mice and observed no adverse effects on body weight, as well significantimpairment of tumour growth in our CREBBP-mutant model only. Finally, we validated thetherapeutic benefit of Disulfiram in vivo, showing that it was safe and effective at reducing tumourgrowth in CREBBP-mutant DLBCL xenografts. Overall, this data supports the provocative hypothesis thatDisulfiram could represent a novel, repurposed treatment option for patients with CREBBP-mutantDLBCL."

IO biomarker • Addiction (Opioid and Alcohol) • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • CREBBP • DLAT • GPX1 • LIAS • SLC30A1 • SOD2

An unexpected role for maea in preventing ferroptosis of erythroblastic island macrophages to support erythropoiesis (ASH 2025) - "Consistent with this, we observed significantly higher levelsof cellular ROS, lipid peroxidation, and intracellular concentration of redox-active ferrous iron (Fe2+) inMaea-deleted EBI macrophages compared to controls. Importantly, Liproxstatin-1, an ferroptosisinhibitor, partially alleviated anemia symptoms, increased the numbers of EBI macrophages and EBIs,reduced levels of ROS as well as lipid ROS in EBI macrophages in the Maeafl/flEpoR-tdTomatoCre mice.Together, our findings uncovered a previously unknown role of Maea in erythropoiesis by protecting EBImacrophages from ferroptosis."

Hematological Disorders • AXL • CD163 • GPX4 • HMOX1 • IGF1 • SAT1 • VEGFB

Liproxstatin-1 Protects SH-SY5Y Cells by Inhibiting H2O2-Induced Excessive Mitophagy and Apoptosis. (PubMed, Int J Mol Sci) - "Pretreatment with 1 μmol/L liproxstatin-1 attenuated the damage by H2O2, suggesting its protective role. Collectively, our results indicated that 500 μmol/L H2O2 induces cytotoxicity through oxidative damage, protein kinase B/ mammalian target of rapamycin pathway inhibition, and aberrant mitophagy, ultimately leading to apoptosis; meanwhile, 1 μmol/L liproxstatin-1 counteracted these effects by preserving mitochondrial function, suppressing excessive mitophagy, and inhibiting apoptotic pathways, thereby protecting SH-SY5Y cells from H2O2-induced cytotoxicity."

Journal • Metabolic Disorders