liproxstatin-1 / Jilin University - LARVOL DELTA

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

Fatty acid-binding protein 5 aggravates psoriasis and psoriasis-like disease through ferroptosis. (PubMed, Cell Death Differ) - "Furthermore, treatment with the ferroptosis inhibitor, liproxstatin-1, suppressed Ps-like skin thickening in DKO* mice, but did not affect the joint phenotype. These results support a functional and disease-relevant link between Fabp5, Gpx4 and ferroptosis in the skin that should be therapeutically exploited."

Journal • Cardiovascular • Dermatitis • Dermatology • Immunology • Inflammation • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Psychiatry • Rheumatology • Seronegative Spondyloarthropathies • FABP5 • GPX4 • IL17A • JUN • JUNB

PRDX1 depletion predisposes to ferroptosis through inhibiting the cAMP pathway in B-cell acute lymphoblastic leukemia. (PubMed, Cancer Gene Ther) - "Ferroptosis was induced in B-ALL cells using erastin...PRDX1 knockdown further reduced the viability of B-ALL cells treated with the ferroptosis activator ML210, and treatment with the ferroptosis inhibitor liproxstatin-1 significantly reversed the suppressive effect of PRDX1 knockdown on xenograft tumor growth. Mechanically, PRDX1 deletion triggered ferroptosis in B-ALL cells by inhibiting the cAMP pathway. PRDX1 deficiency modulates ferroptosis in B-ALL cells by blocking the cAMP pathway, which offer a novel perspective on the pathogenesis of B-ALL."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • ACSL4 • GPX4 • MT-CO2 • PRDX1

Acute kidney injury following fatty liver ischemia-reperfusion injury: indirect protection by hepatic ferroptosis inhibition. (PubMed, Front Physiol) - "In parallel experiments, the lipid peroxidation inhibitor Liproxstatin-1 (Lip-1) was administered prior to hIRI to inhibit ferroptosis...Apoptosis and inflammation are the prominent kidney injury mechanisms involved in AKI following fatty liver IRI. Although ferroptosis may not be directly involved in the renal injury, anti-ferroptotic intervention mitigates AKI, supporting the concept that ferroptosis-mediated liver injury may serve as the primary upstream trigger in this context."

Journal • Acute Kidney Injury • Cardiovascular • Hepatology • Inflammation • Liver Failure • Nephrology • Renal Disease • Reperfusion Injury • Transplantation • ACSL4 • ANXA2

Curcumin Analogues Trigger HMOX1-Mediated Ferroptosis to Halt Endometrial Cancer Growth. (PubMed, bioRxiv) - "Cytotoxicity and colony formation were evaluated using CyQUANT assays, with pharmacological inhibitors (ZnPP, Liproxstatin-1, Z-VAD-FMK) and HMOX1 siRNA to dissect the roles of ferroptosis and apoptosis...HO-3867 and AKT-100 induce HMOX1-mediated ferroptosis and apoptosis, effectively suppressing endometrial cancer cell growth. These findings support the therapeutic potential of curcumin analogues and provide a foundation for in vivo studies targeting HMOX1 in endometrial cancer."

Journal • Endometrial Cancer • Oncology • Solid Tumor • HMOX1

Ferroptosis-related oxidative stress activation in the acute phase of Kawasaki disease. (PubMed, Front Immunol) - "Liproxstatin-1, a specific ferroptosis inhibitor, was applied to determine whether the ferroptosis-related alterations were reversible...Our findings indicate that ferroptosis is activated in KD and may contribute to its pathogenesis. Ferroptosis inhibitor alleviated the associated cellular damage, suggesting that it may represent a potential therapeutic strategy for KD."

Journal • Cardiovascular • Vasculitis

BMAL1-mediated circadian-ferroptosis crosstalk drives neuronal vulnerability after TBI. (PubMed, Free Radic Biol Med) - "Ferroptosis inhibitors, melatonin (MLT) and liproxstatin-1 (Lip-1), alleviated TBI-induced weight loss and neurological dysfunction...Mechanistically, the Bmal1 downregulation sensitized HT-22 neurons to RSL3-induced ferroptosis in vitro by exacerbating oxidative stress and iron overload. Collectively, these findings demonstrated an asymmetric crosstalk, in which circadian clock disruption promotes ferroptosis, and inhibition of ferroptosis feeds back to modulate clock gene expression without restoring behavioral rhythms. This circadian-ferroptosis axis may represent a novel and promising target for therapeutic intervention in post-TBI neuroprotection."

Journal • CNS Disorders • Hematological Disorders • Vascular Neurology • ANXA2 • ARNTL • BMAL1 • CLOCK • PER2

Glyoxalase-1 Inhibition Leads to Ferroptosis Induction in Lung Cancer Cells: A Dual Mechanism of Action of Hydroxamic Acids Derived from Cysteine. (PubMed, ChemMedChem) - "Furthermore, these effects are reversed by Liproxstatin-1, a potent and selective ferroptosis inhibitor. Acute and subacute toxicological assays in mice showed mild toxicity (LD50 > 2000 mg kg-1) and moderate organ damage. These in vitro and in vivo findings suggest that ferroptosis induction may serve as a side effect of Glo-1 inhibition, making compound 2 a promising lead for further development and optimization."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

PRMT1 drives oral squamous cell carcinoma progression by activating STAT3 and suppressing ferroptosis via GPX4. (PubMed, Cell Biosci) - "PRMT1 drives OSCC aggressiveness by methylating and activating STAT3. This axis promotes chemoresistance and oncogenic phenotypes primarily by suppressing ferroptosis through STAT3-mediated transcriptional upregulation of GPX4. Targeting PRMT1 represents a promising strategy to overcome chemoresistance and inhibit progression in OSCC."

IO biomarker • Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • GPX4 • IL6 • MYC • PRMT1 • STAT3

Inhibiting ferroptosis enhances ex vivo expansion of human haematopoietic stem cells. (PubMed, Nat Cell Biol) - "Inhibiting ferroptosis with liproxstatin-1 or ferrostatin-1 markedly increases the expansion of cord blood and adult HSCs consistently across donors in both widely used serum-free cultures and recently reported chemically defined conditions...Mechanistically, ferroptosis blockade is accompanied by upregulated ribosome biogenesis and cholesterol synthesis, increasing levels of 7-dehydrocholesterol-a potent endogenous ferroptosis inhibitor that itself promotes HSC expansion. Crucially, this approach enhances yields of therapeutically genome-modified HSCs, paving a path for clinical applications."

Journal • Preclinical • Hematological Disorders • Transplantation

Nanoparticle-Mediated Ferroptosis for Cancer Therapy: Mechanisms and Therapeutic Strategies. (PubMed, Nanotechnol Sci Appl) - "This distinction requires the use of lipophilic radical-trapping antioxidants (eg, ferrostatin-1, liproxstatin-1), iron chelators, and evidence implicating glutathione peroxidase 4 (GPX4) or the system Xc- antiporter...Finally, we discuss translational challenges, including tumour microenvironment heterogeneity, NP protein corona dynamics, clearance and off-target effects. We aim to provide a framework that links NP design to ferroptotic mechanisms and clinically relevant outcomes, offering clear criteria and priorities for future research."

Journal • Review • Oncology • GPX4

Gallic acid: A promising anti-non-small cell lung cancer compound targeting early growth response protein-1 for apoptosis and ferroptosis (ESMO 2025) - "As anticipated, the application of the ferroptosis inhibitor liproxstatin-1 or EGR1 knockdown effectively reversed GA-induced cell death...Conclusions This multimodal mechanism, simultaneously engaging apoptosis and ferroptosis through EGR1 coordination, positions GA as a promising therapeutic candidate for NSCLC. Legal entity responsible for the study Affiliated Hospital of Shandong University of Traditional Chinese Medicine."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGR1 • GPX4 • SLC7A11 • TGFB1

Berberine sensitizes liver cancer cells to sorafenib by inducing SETDB1/NQO1/p53-dependent ferroptosis and genomic instability. (PubMed, Eur J Pharmacol) - "Compared with sorafenib treatment alone, additional berberine treatment induced more severe mitochondrial dysfunction and ROS accumulation, following exacerbation of lipid peroxidation, which were abolished by ferroptosis inhibitors liproxstatin-1 and ferrostatin-1. Additionally, we demonstrated NQO1 activation induced by combined treatment was due to SETDB1 inactivation, following ERVs induction and genome instability, which may be another factor for lipid peroxidation and ferroptosis. Collectively, berberine has great potential to be used as a novel chemo-enhancer to improve the efficacy of sorafenib -based therapy."

Journal • Hepatocellular Cancer • Liver Cancer • Metabolic Disorders • Oncology • Solid Tumor • Targeted Protein Degradation • NQO1 • SETDB1

EXPLOITING CANCER IRON METABOLISM: A TARGETED APPROACH FOR SELECTIVE THERAPIES (UEGW 2025) - "As a proof-of-concept, we evaluated the therapeutic potential of 5b, a prodrug coupled with doxorubicin (DOX), which releases this cytotoxic payload upon activation by the labile Fe(II) pool in the cytoplasm of cancer cells...To confirm iron-dependency, HCT116 cell viability was assessed upon co-incubation with 5b and iron chelator deferoxamine (DFO)...The significant decrease in cell viability induced by 5b (p < 0.0001) was rescued by the iron chelator DFO and by the ferroptosis inhibitor liproxstatin-1 (p < 0.01) but not by pan-caspase inhibitor Zvad, suggesting that ferroptosis may be the primary mechanism of cell death... Prodrug 5b efficiently released its DOX payload in response to the cytoplasmatic labile Fe(II), effectively reducing cancer cell viability both in vitro and in vivo, while demonstrating significantly lower toxicity compared to DOX itself. Given its Fe(II)-dependent activation, 5b represents a promising strategy to exploit cancer cell iron..."

Brain Cancer • Breast Cancer • CNS Disorders • Colorectal Cancer • Fibrosis • Genito-urinary Cancer • Glioblastoma • Immunology • Oncology • Prostate Cancer • Psychiatry • Solid Tumor • KRAS

Ferroptosis-targeting compounds modulate cancer cell cytotoxicity and migration: Insights from in vitro and in silico analyses. (PubMed, J Trace Elem Med Biol) - "These findings nominate multi-selenoproteins inhibition as a promising strategy to overcome ferroptosis resistance."

Journal • Preclinical • Oncology • GPX4 • PRDX6

DOES CHOLANGIOCYTE FERROPTOSIS PROMOTE A PRO-FIBROGENIC MACROPHAGE PHENOTYPE IN CHOLESTASIS? (AASLD 2025) - "Ferroptosis was induced in vitro in normal human cholangiocyte cell lines (NHC, H69) by RSL3 (potent inducer of ferroptosis) and measured by propidium iodide uptake and flow cytometry using the fluorescent sensor for lipid peroxidation BODIPY C11...Fourteen oxidized phospholipids were detected in the bile of DDC-fed mice, but not in chow-fed mice, and decreased in mice simultaneously receiving the ferroptosis inhibitor liproxstatin 1 (Lip-1)... Our data identify cholangiocyte ferroptosis as a potential contributor to the fibroinflammatory biliary injury in human and murine cholestasis by releasing oxidized lipid mediators of macrophage profibrotic polarization."

Cholestasis • Fibrosis • Hepatology • Immunology • ABCB4 • ANXA2 • IL17A • PDGFB • TGFB1

Pharmacological Inhibition of Ferroptosis Attenuates Experimental Abdominal Aortic Aneurysm Formation. (PubMed, Arterioscler Thromb Vasc Biol) - "Mechanistically, in vitro studies demonstrate that liproxstatin-1 treatment of macrophages mitigated ferroptosis and MMP9 expression, as well as the crosstalk with aortic smooth muscle cells by downregulating MMP2 secretion. Taken together, this study demonstrates that pharmacological inhibition by liproxstatin-1 mitigates macrophage-dependent ferroptosis, contributing to the inhibition of aortic inflammation and remodeling during AAA formation."

Journal • Cardiovascular • Hematological Disorders • Inflammation • Thrombosis • ELANE • MMP2 • MMP9

4-HDHA, a DHA metabolite screened by targeted lipidomic, alleviates DSS-induced colitis by inhibiting apoptosis and reducing inflammation. (PubMed, Int Immunopharmacol) - "In this study, we observed that the lipid peroxide scavenger Liproxstatin-1 unexpectedly promoted TNF-α-induced apoptosis in HT-29 cells and murine colonic organoids, in contrast to the protective effects previously reported for typical peroxide scavengers in UC...Furthermore, 4-HDHA suppressed NF-κB signaling and apoptosis via PPARγ activation. Collectively, these findings demonstrate that 4-HDHA, identified through targeted lipidomics, attenuates DSS-induced colitis by reducing apoptosis and inflammation through PPARγ activation, highlighting its potential as a promising therapeutic agent for UC."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • PPARG • TNFA

Ferroptosis involved in inhaled polystyrene microplastics leaded myocardial fibrosis through HIF-ROS-SLC7A11/GPX4 Pathway. (PubMed, J Environ Sci (China)) - "Liproxstatin-1 (Lip-1), a ferroptosis inhibitor, significantly ameliorated MPs-induced cardiomyocyte fibrosis and ferroptosis. We further demonstrated that inhibition of hypoxia-inducible factor α (HIF-α) and oxidative stress ameliorated PS-MPs-induced cardiomyocyte ferroptosis, and thus upregulation of the HIF pathway and oxidative stress may be the upstream mechanism of MPs-induced ferroptosis in myocardial fibrosis. Above all, our study demonstrated that MPs exposure resulted in cardiac fibrosis via the HIF-ROS-SLC7A11/GPX4 signaling pathway."

Journal • Cardiovascular • Fibrosis • Immunology • ANXA2 • GPX4 • SLC7A11

Fufang Changtai Decoction Inhibites Colorectal Cancer Through Ferroptosis: Investigation of the Underlying Mechanism (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban) - "To assess the role of ferroptosis, ferroptosis inhibitor liproxstatin-1 (Lip-1) was co-administered with FFCT-containing serum...Immunofluorescence analysis of clinical CRC tissue microarrays revealed that NQO1 expression was significantly higher in tumor tissues than in adjacent non-tumor tissues (P < 0.001). FFCT may induce intracellular ferroptosis by downregulating the oncogenic gene NQO1, thereby exerting anti-CRC effects."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ANXA2 • NQO1 • PACERR • PTGS2 • TP53