erastin / Whitehead Institute for Biomedical Research, Dana-Farber Cancer Institute, Columbia University, Prolexys - LARVOL DELTA

Polyunsaturated fatty acids control lipid membrane dynamics and ferroptosis sensitivity in B-cell lymphoma (ASH 2025) - "We uncovered that B-cell lymphomas are highly enriched in PUFA and selectively dependent on pro-ferroptotic PUFAmetabolism to maintain competitive fitness and lipid membrane properties, which endows them with anintrinsic vulnerability to ferroptotic cell death. Our comparative analyses of public drug screening data (CTD, GDSC) and a validation screen weperformed uncovered that B-cell lymphomas are the most sensitive type of tumor to all evaluatedferroptosis inducers, including GPX4 inhibitors (RSL3, ML210), the inhibitor of the cystine/glutamateantiporter system Xc- erastin, and the iron oxidizer FINO2. We show that B-cell lymphomas are selectively dependent on PUFA metabolism to maintainmembrane properties and competitive fitness. However, this intrinsic metabolic dependency is a keyfactor making them highly vulnerable to ferroptosis. Our findings also provide insight into B-celllymphoma metabolism and lipid membrane dynamics, and how it could be leveraged as a..."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • ACSL3 • ACSL4 • GPX4

FerroEVs drive serial propagation of pharmacologically induced ferroptosis in acute leukemia cells (ASH 2025) - "Here, we provide proof of concept that ferroptosis-associated extracellularvesicles (ferroEVs) mediate death propagation in leukemia cells.Erastin treatment of U937 leukemia cells (IC₅₀: 19.6 µM) induced ferroptosis, as evidenced by increasedreactive oxygen species (ROS; 40.1% vs. 8.1%), elevated fatty acyl-CoA synthetase long-chain familymember 4 (FACL4/ACSL4), reduced glutathione peroxidase 4 (GPX4) expression, increased lipidperoxidation (12.3 vs. 7.2), and mitochondrial shrinkage; all effects were reversed by ferrostatin-1,confirming ferroptosis as the predominant mode of cell death...In line with thissignature, recipient cells exposed to ferroEVs exhibited sustained ROS accumulation and lipidperoxidation—hallmarks of ferroptotic stress—supporting a model in which ferroEV cargo rewiresantioxidant defenses and propagates ferroptotic cell death across neighboring leukemia cells.Collectively, these findings demonstrate that ferroptotic leukemia cells actively..."

Hematological Malignancies • Leukemia • ACSL4 • ANXA5 • CASP3 • CD63 • GPX4 • TSG101

Ferroptosis escape in AML stem cells uncovered by single-cell profiling and reversed by STAT3/NRF2 inhibition (ASH 2025) - "These cells were treated with STAT3 inhibitor C188-9 or STAT3-NRF2dual inhibitor (Brusatol) and the effect on cell proliferation was determined using CCK-8 assay, geneexpression by qPCR, flow cytometry was used for the detection of lipid ROS levels by Bodipy dye andintracellular iron estimation were performed...Moreover, acombination of NRF2-STAT3 inhibitor potentiated the effect of ferroptosis inducers RSL3 and Erastin andenhanced the cytotoxicity in LSCs.Our scRNAseq analysis of enriched AML LSCs revealed and dissected the mechanistic differencesbetween LSCs and non-LSCs...Our findings suggest that promoting ferroptosis is indeed apromising strategy to combat chemoresistance in AML. Therefore, dual targeting of NRF2-STAT3 alongwith ferroptosis inducers hold potential as adjuvant therapy by promoting ferroptosis-mediated celldeath in AML LSCs."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CD34 • FTH1 • GPX4 • KIT • STAT3

Selenocysteine dependency renders central nervous system leukaemia therapeutically sensitive to ferroptosis (ASH 2025) - "Exposure of both B- and T-ALLcells to this media resulted in significantly increased lipid peroxidation, triggered the GSH stress markerCHAC1, and increased sensitivity to the ferroptosis-inducing compounds RSL3 (inhibitor of GPX4) andErastin (inhibitor of cystine antiporter System XC-)...GSH disruption (by cystine deprivation in CSF media, or Erastin) inLRP8KO and SEPHS2KO cells resulted in increased lipid peroxidation, selective loss of GPX4 expression andenhanced ferroptosis... By comprehensive in vitro and in vivo characterisation we have identified a pivotalmechanism underpinning leukaemic survival in the CNS-niche. We show that the unique biochemicalcomposition of CSF drives a dependence on selenocysteine biosynthesis which presents a targetablemetabolic vulnerability. Our demonstration that Auranofin, a repurposed FDA-approved oral compoundwith excellent tolerability, leads to selective eradication of CNS-leukaemia in PDX models paves the wayfor clinical advances..."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • GPX4 • SELENOP • SEPHS2

Inhibition of super-enhancer-driven lncRNA SHC alleviates coronary microembolization-induced myocardial injury by inhibiting cardiac ferroptosis. (PubMed, Eur J Pharmacol) - "A significant upregulation of lncRNA SHC was found in heart tissue following CME and Erastin-induced H9c2 cardiomyocytes...Furthermore, lncRNA SHC acted as a sponge for miR-26b-3p to promote oxidized low-density lipoprotein receptor 1 (Olr1) expression, which partially accounted for ferroptosis-dependent myocardial injury. In conclusion, these data suggest that the lncRNA SHC, driven by SE, contributes to cardiac ferroptosis and myocardial injury by targeting the miR-26b-3p/Olr1 cascade, and thus may be a promising therapeutic target to improve the prognosis of patients with CME."

Journal • Acute Coronary Syndrome • Cardiovascular • Dyslipidemia • OLR1

RNPS1 Promotes the Progression of Nonsmall Cell Lung Cancer via ETV4-Mediated Ferroptosis. (PubMed, DNA Cell Biol) - "Furthermore, RNPS1 overexpression attenuated erastin-triggered ferroptosis by suppressing the accumulation of lipid ROS and malondialdehyde, as well as by preventing the depletion of glutathione...Importantly, blocking ETV4 expression partially reversed RNPS1 overexpression-mediated suppression of ferroptosis. Collectively, these results support the notion that RNPS1 acts as a novel suppressor of ferroptosis in NSCLC progression."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ETV4 • RNPS1 • TCF4

Therapeutic targeting SPI1 in combination with erastin promotes ferroptosis in ccRCC. (PubMed, Commun Biol) - "Mechanistically, SPI1 transcriptionally suppresses ACSL4 expression through the EZH2/H3K27me3 pathway, leading to inhibition of intracellular lipid peroxidation. Thus, SPI1 knockdown synergizes with erastin to promote lipid peroxidation and ferroptosis, suggesting that targeting SPI1 may represent a promising therapeutic strategy for renal cell carcinoma."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ACSL4 • EZH2 • SPI1

Ferroptosis and Radiotherapy in Lung Cancer. (PubMed, Cells) - "Ferroptosis represents a promising modern adjunct to a traditional therapeutic strategy. Future work should focus on rigorous dosage standards to avoid unintended toxicity, repurposing of currently available drugs into ferroptosis inducers, and establishment of safety protocols to begin the pathway towards clinical studies."

Journal • Review • Hematological Disorders • Lung Cancer • Oncology • Solid Tumor

TPX2 promotes ferroptosis in LPS-induced C28/I2 chondrocytes via NF-κB p65-mediated downregulation of GPX4 and SLC7A11. (PubMed, Mol Biol Rep) - "Our in vitro findings suggest that TPX2 may promote ferroptosis in LPS-induced C28/I2 chondrocytes via NF-κB p65 signaling, reducing antioxidant defenses. Further in vivo and clinical studies are needed to clarify its role and therapeutic potential in OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • GPX4 • NFKB1 • RELA • SLC7A11 • TPX2

BCL11A-triggered IFI6 inhibition reduces glioma cell resistance to temozolomide by promoting ferroptosis. (PubMed, Neurol Res) - "The rescue experiments (overexpression of BCL11A combined with IFI6 or ferroptosis activator Erastin) were conducted to clarify the mechanism. Co-overexpression of IFI6 rescued the phenotype. This study reveals that BCL11A promotes ferroptosis by transcriptional inhibition of IFI6, thereby reducing TMZ resistance in glioma cells, providing a new strategy for combined targeting of IFI6 and ferroptosis."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • BCL11A

Umbilical cord mesenchymal stem cells protect against obstetric deep venous thrombosis in rats by suppressing ferroptosis. (PubMed, Stem Cell Res Ther) - "In vitro, erastin induced typical features related to ferroptosis...Furthermore, the function of ALOX15 was verified in vitro and in vivo. In conclusion, this study suggested that UCMSCs mitigated the inflammation levels, facilitated recanalization, and improved pregnancy outcomes in cases of obstetric DVT by mitigating ferroptosis within endothelial cells."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Inflammation • Obstetrics • Thrombosis • Transplantation • ALOX15

Synthesis and evaluation of lupeol-derived triterpenic azines as potential neuroprotective agents. (PubMed, RSC Med Chem) - "Since ferroptosis is a cell death mechanism implicated in PD, we further examined the effects of these compounds in N27 dopaminergic neurons exposed to the ferroptosis inducers RSL3 and erastin. Among the tested derivatives, 4c exhibited a remarkable protective effect against RSL3-induced ferroptosis, which was comparable to ferrostatin-1, displaying an IC50 value of 9.1 μM. These findings support the development of triterpenic azines as neuroprotective agents and warrant further investigation in preclinical PD models."

Journal • CNS Disorders • Movement Disorders • Neuroblastoma • Oncology • Parkinson's Disease • Solid Tumor

Chaihu Guizhi Ganjiang decoction attenuates chronic pancreatitis by suppressing acinar cell ferroptosis via regulating p53/SLC7A11/GPX4 pathway. (PubMed, J Ethnopharmacol) - "Our findings demonstrate that CGGD suppresses ferroptosis in pancreatic acinar cells via the p53/SLC7A11/GPX4 axis, thereby elucidating a novel therapeutic mechanism of CGGD for the treatment of CP."

Journal • Fibrosis • Immunology • Inflammation • Pancreatitis • GPX4 • SLC7A11 • TFRC

MICU1 promotes Ca2+ homeostasis and curbs ferroptosis to attenuate brain tissue damage in rats with postoperative cognitive dysfunction. (PubMed, Brain Res) - "MICU1 promotes Ca2+ homeostasis, inhibits ferroptosis and ROS production, and alleviates brain tissue damage in POCD rats."

Journal • Preclinical • Anesthesia • Cognitive Disorders • Inflammation

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

MeCP2 suppresses ferroptosis to drive EMT in retinal pigment epithelial cells: Implications for PVR pathogenesis. (PubMed, Mol Med Rep) - "In the present study, a scratch assay demonstrated that MeCP2 enhanced ARPE‑19 cell migration, which was markedly suppressed by erastin...MeCP2 suppressed ferroptosis through GPX4 upregulation, using this pathway to orchestrate EMT, thus revealing a critical GPX4‑dependent mechanism that links ferroptosis to RPE plasticity in PVR. These findings highlighted ferroptosis modulation as a promising therapeutic strategy for PVR."

Journal • Retinal Disorders • CDH1 • CDH2 • GPX4 • SLC7A11

Ultrafine garlic powder alleviates non-alcoholic steatohepatitis by inhibiting hepatocyte ferroptosis and modulating ERK-dependent oxidative stress. (PubMed, Front Pharmacol) - "UGP lowered intracellular Fe2+ levels in hepatocytes from 68.72% to 34.48% (n=4) and significantly protected hepatocytes from erastin-induced ferroptosis (cell viability: UGP treatment 23.46% vs erastin stimulation 53.91%, n = 4, p <0.0001).In the acute liver fibrosis model induced by methionine- and choline-deficient diet supplemented with 60 kcal% fat (CDHF), UGP significantly improved liver histology...RNA-seq analysis revealed that UGP modulated key pathways, including fatty acid metabolism and the MAPK signaling pathway, and suppressed ROS production, further highlighting its therapeutic potential in NASH treatment. Taken together, these data suggest that UGP alleviates NASH by inhibiting hepatocyte ferroptosis and modulating ERK-dependent oxidative stress, supporting its potential as a therapeutic agent."

Journal • Addiction (Opioid and Alcohol) • Fibrosis • Hepatitis B • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Unveiling the role of Hedgehog signaling pathway in mitigating methylisothiazolinone-induced anxiety in zebrafish. (PubMed, Ecotoxicol Environ Saf) - "In vitro studies using Pac2 cells further corroborated that inhibition of the Hedgehog pathway alleviates the increase in lipid peroxidation induced by the ferroptosis inducer Erastin. Collectively, these results elucidated the molecular regarding MIT-induced neurotoxicity and offer potential preventive and interventional strategies for addressing toxicity associated with this class of compounds."

Journal • Mood Disorders • Psychiatry • GLI1 • GPX4

The CHPT-pSTAT3-SLC7A11 signaling axis controls progression and ferroptosis susceptibility of pancreatic cancer. (PubMed, Transl Oncol) - "The CHPT1-pSTAT3-SLC7A11 axis governs ferroptosis-dependent chemoresistance in PDAC. Dual targeting of CHPT1 and ferroptosis pathways represents a promising strategy to overcome GEM resistance, highlighting metabolic-kinase crosstalk as a therapeutic vulnerability."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PTPN1 • SLC7A11

ATAD2 drives melanoma growth and progression and inhibits ferroptosis. (PubMed, EMBO Rep) - "The ferroptosis inducer erastin also inhibits melanoma growth. Combining the ATAD2 inhibitor BAY-850 with the MEK inhibitor trametinib potently suppresses melanoma growth. Our study identifies ATAD2 as a key driver of melanoma and provides a rationale for targeting ATAD2 in conjunction with the MAPK pathway to treat melanoma."

Journal • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • ATAD2 • BRAF • E2F1 • GPX4 • NRAS

ELOVL5 Regulates Ferroptosis in Breast Cancer Cells. (PubMed, Dokl Biochem Biophys) - "In this work, the effect of ELOVL5 knockdown on the dynamics of ferroptosis induction in MDA-MB-231 cells under the influence of docosahexaenoic acid (DHA) and erastin was investigated...The protective effect of ferroptosis inhibitors (ferrostatin-1 and deferoxamine) confirmed the involvement of this pathway in the observed effects. Differences in the expression of genes associated with oxidative stress, inflammation and proliferation were also revealed, indicating different molecular trajectories of ferroptosis in cells with different ELOVL5 gene expression. Thus, the present study deepens the understanding of the contribution of the ELOVL5 gene to the regulation of ferroptosis and can be used in the development of targeted therapy for breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor

Suppression of TRIP13 Induces Metabolic Changes and Potentiates Ferroptosis in Multiple Myeloma (ASH 2023) - "Moreover, lipid peroxidation and PTGS2 were increased in TRIP13-KO cells after Erastin treatment, indicating that these cells were more vulnerable to ferroptosis...By suppressing TRIP13, we observed increased sensitivity of MM cells to bortezomib, leading to enhanced ferroptosis-mediated cell death and prolonged mouse survival...Moving forward, our future investigations will concentrate on unraveling the precise molecular mechanisms underlying TRIP13-mediated alterations in cell metabolism. Additionally, we plan to explore the potential synergistic effects of TRIP13 inhibition in combination with metabolic targeted treatments, such as venetoclax, to further enhance therapeutic outcomes in MM."

Hematological Malignancies • Multiple Myeloma • Oncology • GPX4 • NCOA4 • PACERR • PTGS2 • TFRC • TRIP13

FOSL2 promotes ferroptosis resistance in Glioblastoma (SNO 2025) - "Notably, in FOSL2-knockout GBM xenograft models, the Erastin+TMZ treatment group exhibited the lowest expression of Ki-67, GPX4, and SLC7A11. Together, our findings reveal the prominent role of FOSL2 in regulating ferroptosis and highlight the potential therapeutic application of TMZ combined with ferroptosis-inducing drugs."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • ACSL4 • FOSL2 • GPX4 • SLC7A11

THRAP3 promotes ferroptosis resistance in acute myelocytic leukemia through SLU7-mediated alternative splicing of GIT2. (PubMed, Nat Commun) - "THRAP3 overexpression promotes resistance of AML cells to RSL3/erastin-induced ferroptosis via inhibiting iron accumulation and promoting GSH synthesis. Inhibition of GIT2 Exon14 skipping reverses THRAP3-induced ferroptosis resistance in vitro and in vivo. Altogether, THRAP3 contributes to ferroptosis resistance of AML cells via interaction with SLU7 to trigger GIT2 Exon14 skipping, which suggests THRAP3 to be a therapeutic target for AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Metabolic Functions and Mechanisms of Selenium, Selenocysteine, and GPX4 Mediated Immune Regulation Through Autophagy in Solid Tumors. (PubMed, Food Sci Nutr) - "In the autophagy mediated by copper and erastin (a ferroptosis inducer), the autophagy receptors TAX1BP1 and SQSTM1 can promote the degradation of GPX4, effectively reducing the resistance of cancer cells to ferroptosis...In this review, we conduct a comprehensive and in-depth analysis of the roles played by selenoproteins derived from selenium metabolism in the regulation of immune cells associated with immune diseases. Moreover, we elaborate in detail on the effects of GPX4 in relation to ferroptosis in solid tumors under the influence of autophagy-mediated immunomodulation."

Journal • Review • Immunology • Oncology • Solid Tumor • GPX4 • IL10 • SELENOP • SQSTM1