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

A Dual-Organelle Fluorescent Probe for Visualizing Intracellular Microviscosity Dynamics. (PubMed, J Fluoresc) - "Using multiple cellular stress models-including LPS stimulation, oleic-acid treatment, nystatin exposure, and erastin-induced ferroptosis-ZKW effectively reported viscosity elevations at the subcellular level. These results establish ZKW as a robust and versatile tool for probing microviscosity heterogeneity in living cells and for facilitating studies of viscosity-associated physiological and pathological processes."

Journal

Nrf2/HO-1-dependent inhibition of ferroptosis underlies the antioxidant effects of 5-O-methylvisammioside in colitis. (PubMed, Front Immunol) - "In parallel, erastin-challenged Caco-2 cells were used to test whether MeV directly restrains ferroptosis; Nrf2 knockdown probed pathway dependency...MeV alleviates experimental colitis, at least in part by activating Nrf2/HO-1 to restrain ferroptosis and preserve epithelial barrier integrity. These findings nominate MeV as a ferroptosis-targeting candidate for colitis."

Journal • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • ACSL4 • GPX4 • OCLN • TJP1

Gene expression profiling identifies ferroptosis-related genes and pathways in human colon cancers cell lines. (PubMed, Front Mol Biosci) - "Erastin (ER), a small-molecule compound, induces ferroptosis through ROS accumulation...Our findings highlight ASNS, CHAC1, PCK2, DDIT4, and ATF3/4 as potential biomarkers for ferroptosis in CRC. Monitoring the expression of these genes may help identify patients who are responsive to ferroptosis inducers and facilitate the development of personalized treatment strategies."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • ATF3 • CHAC1 • DDIT4 • NQO1

TIMELESS Promotes LUAD Growth via Suppressing Transferrin-Mediated Ferroptosis and Reprograms the Tumor Microenvironment against Anti-PD-1 Immunotherapy. (PubMed, Cancer Commun (Lond)) - "In an orthotopic lung cancer mouse model treated with erastin (a ferroptosis inducer) and programmed cell death protein 1 (PD-1) blockade, the role of TIMELESS in therapeutic response was assessed via flow cytometry and multiplex immunofluorescence (mIF)... TIMELESS recruits CNOT3 to accelerate TF mRNA degradation, thereby suppressing ferroptosis and promoting LUAD growth. These findings suggest that the TIMELESS/TF regulatory axis may be a promising therapeutic target for LUAD."

Biomarker • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCR4 • CNOT3 • PD-L1 • TIMELESS

Expression of Antioxidant Defense Genes Determines Synergistic Ferroptosis Induction by the Combination of Erastin and Omega-3 Docosahexaenoic Acid in Prostate Cancer Cells. (PubMed, Dokl Biochem Biophys) - "At the same time, known ferroptosis inhibitors, ferrostatin-1 and deferoxamine, effectively prevented cell death, indicating the specificity of the mechanism of action. Transcriptomic analysis of cell lines differing in sensitivity to the combination revealed activation of antioxidant systems in more resistant cells (in particular, pronounced expression of the NQO1 and GCLM genes responsible for the reduction of quinones to hydroquinones and the synthesis of glutathione, respectively). The obtained results indicate the high synergistic potential of the erastin-DHA combination for ferroptosis induction and open new possibilities for the development of combined approaches to the therapy of resistant tumors."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • NQO1

6PPD-Q exposure promotes hepatocellular carcinoma progression and confers resistance to ferroptosis. (PubMed, Ecotoxicol Environ Saf) - "Here, we evaluated the effects of 6PPD-Q on HCC cells by assessing transcriptomic profiles, proliferation, migration, and erastin-induced/Ferrostatin-1-inhibited ferroptosis, and interrogated the regulatory role of zinc finger X-linked duplicated family zinc finger C (ZXDC) using knockdown and overexpression approaches...In parallel, multi-algorithm immune infiltration analyses showed that the 6PPD-Q-related gene risk score was significantly associated with multiple immune populations, with macrophage M0 cells showing a significant positive correlation with the risk score (R = 0.30, p < 0.001). Collectively, these findings identify a 6PPD-Q/ZXDC axis that links environmental exposure to HCC malignant progression and ferroptosis resistance, suggesting ZXDC as a potential biomarker and intervention target for HCC prevention and therapy."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

VAMP7 governs ferroptosis suppression and cisplatin resistance in esophageal cancer: a dual-targeting therapeutic paradigm. (PubMed, Cancer Cell Int) - "Therapeutically, co-administration of ferroptosis agonists (RSL3/Erastin) with cisplatin abrogated VAMP7-mediated resistance, evidenced by suppressed xenograft growth and amplified mitochondrial pathology in preclinical models. This work identifies VAMP7 as a novel ferroptosis-chemoresistance nexus in EC, offering a translational framework for overcoming cisplatin refractoriness through coordinated inhibition of VAMP7 signaling and ferroptosis potentiation."

Journal • Esophageal Cancer • Oncology • GPX4 • VAMP7

Bone-Targeting Selenium-Doped Carbon Dot-Based Nanoparticles for Ferroptosis Suppression and Osteogenesis Against Postmenopausal Osteoporosis. (PubMed, Adv Healthc Mater) - "In this study, we have developed bone-targeting selenium-doped carbon dots conjugated with alendronate (ASCDs) with the dual functionality of suppressing ferroptosis and promoting osteogenesis. In vitro, ASCDs mitigated erastin-induced ferroptosis in osteoblasts and bone-marrow mesenchymal stem cells by activating the system Xc--GSH-GPX4 antioxidant pathway, which reduced lipid peroxidation and restored mitochondrial function...Proteomics and biochemical analyses further validated that ASCDs exert therapeutic effects by rescuing GPX4 expression and redox homeostasis. Such dual-functional carbon dots present a targeted strategy to treat PMOP by concurrently inhibiting ferroptosis and restoring bone formation."

Journal • Osteoporosis • Rheumatology • GPX4 • RUNX2

Valproic Acid Inhibits Ferroptosis and Improves Bone Integration in OVX Rats Through the AMPK/SIRT1 Pathway. (PubMed, Kaohsiung J Med Sci) - "Mechanistic studies reveal that SIRT1-siRNA counteracts the beneficial effects of VPA in Erastin-treated BMSCs. VPA improves bone integration in OVX rats by activating the AMPK/SIRT1 pathway and inhibiting ferroptosis."

Journal • Preclinical • Osteoporosis • Rheumatology

Neuroprotective and anti-inflammatory activity of Wyethia species: therapeutic potential for neurodegenerative diseases. (PubMed, Front Pharmacol) - "We evaluated protection against oxytosis/ferroptosis (induced by glutamate, erastin, and RSL3) in HT22 neuronal cells, energy loss using an ischemia assay in HT22 cells, and LPS-induced inflammation in BV2 microglial cells. This highlights the complexity of phytochemical profiles and the potential presence of potent constituents beyond phenolics. These findings position Wyethia as a promising source of dual-action neuroprotective agents that target both oxytosis/ferroptosis and inflammation, warranting further phytochemical investigation."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Inflammation

HSF4 alleviates ferroptosis in colorectal cancer through transcriptional regulation of MBOAT1/2. (PubMed, Funct Integr Genomics) - "This study found that HSF4 overexpression markedly attenuated Erastin-induced cell death and mitochondrial damage in HT29 and HCT116 cells...In vivo experiments, MBOAT1/2 knockdown effectively reduced tumor volume and downregulated the number of Ki-67-positive cells, GPX4, and SLC7A11, while upregulating ACSL4. In conclusion, HSF4 alleviates ferroptosis in CRC cells and facilitates tumor progression by upregulating MBOAT1/2 transcription, thereby limiting lipid peroxidation and Fe2+ accumulation."

Journal • Colorectal Cancer • Metabolic Disorders • Oncology • Solid Tumor • ACSL4 • ATXN1L • GPX4 • HSF4 • SLC7A11

Silencing CCL5 suppresses ferroptosis to alleviate calcific aortic valve disease through chemokine pathway inhibition. (PubMed, Atherosclerosis) - "CCL5 promoted CAVD progression by activating the chemokine signaling pathway to induce ferroptosis. Targeting CCL5 may offer a novel therapeutic strategy for CAVD."

Journal • Cardiovascular • APOE • CCR4 • CXCL12 • CXCR4

A rapid-response NIR fluorescent probe for imaging Cys/Hcy in ferroptosis and inflammation models. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Furthermore, 1a was utilized to monitor the depletion of mitochondrial Cys/Hcy during Erastin-induced ferroptosis and to evaluate the restorative effects of inhibitors ferrostatin-1 (Fer-1) and N-acetyl-l-cysteine (NAC), providing visual evidence of their distinct regulatory roles. Additionally, the probe could track the consumption of mitochondrial biothiols in an inflammatory model, underscoring its potential for studying redox imbalances in inflammatory processes."

Journal • Inflammation

Ferroptosis in Cholangiocarcinoma Therapy: Molecular Mechanisms, Pharmacological Modulation and Opportunities for Drug Development. (PubMed, Drug Dev Res) - "In addition, the ferroptosis inducers erastin and RSL3 are capable of enhancing the efficacy of traditional therapies and seeking solutions for the chemoresistance problem. The hurdles to be overcome are finding reliable biomarkers for the prediction of ferroptosis sensitivity and designing targeted delivery systems for minimal off-target effects. Clinically, these techniques offer novel concepts in the treatment of CCA, making further research key to these conclusions being adopted in practice."

Journal • Review • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • ACSL4 • SLC7A11

MED12 Dictates Epithelial Ovarian Cancer Cell Ferroptosis Sensitivity via YAP-TEAD1 Signaling. (PubMed, Int J Mol Sci) - "Using CRISPR/Cas9-mediated knockout and rescue experiments in EOC cell lines, we demonstrate that MED12 deficiency significantly enhances sensitivity to ferroptosis inducers (RSL3 and Erastin), as evidenced by reduced IC50 values...Pharmacological inhibition of YAP with verteporfin or siRNA-mediated TEAD1 knockdown reverses ferroptosis sensitivity in MED12-deficient cells, confirming pathway specificity. These findings establish MED12 as a modulator of the YAP-TEAD1-ferroptosis axis and suggest that targeting this pathway could overcome chemoresistance in MED12-deficient EOC. Our work provides a mechanistic foundation for exploiting ferroptosis induction as a therapeutic strategy in ovarian cancer."

Journal • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCN1 • CTGF • TEAD1

Electroacupuncture ameliorates ulcerative colitis by suppressing ferroptosis via the JAK2/STAT3 signaling pathway. (PubMed, Chin Med) - "EA may alleviate ferroptosis in colonic epithelial cells by inhibiting the JAK2/STAT3 pathway, significantly reducing oxidative stress injury, improving intestinal mucosal barrier integrity, and inhibiting the DSS-induced inflammatory cascade in UC mice. This study provides important modern scientific evidence for the application of acupuncture therapy in treating gastrointestinal diseases."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Stress Ulcer • Ulcerative Colitis

RICTOR-mediated GPX4 downregulation regulates chondrocyte ferroptosis in osteoarthritis progression. (PubMed, Int Immunopharmacol) - "This study aims to investigate the role of RICTOR in chondrocyte ferroptosis and to explore the RICTOR-ferroptosis axis as a potential therapeutic target.First, we observed elevated RICTOR expression in cartilage from OA patients and destabilization of the medial meniscus (DMM) mice, as well as in erastin-treated OA chondrocytes...Moreover, the RICTOR inhibitor JR-AB2 ameliorated cartilage degradation in the DMM-induced OA mouse model and mitigated the decline of GPX4 in vivo. Overall, our results indicate that RICTOR induces ferroptosis in OA by regulating GPX4 expression."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • COL2A1 • GPX4 • MMP13 • RICTOR

Cytochrome c Oxidase Subunit COX4-1 Reprograms Erastin-Induced Cell Death from Ferroptosis to Apoptosis: A Transmitochondrial Study. (PubMed, Antioxidants (Basel)) - "These findings demonstrate that mitochondrial COX4-1 rewires redox metabolism and diverts cell-death signaling away from ferroptosis toward apoptosis. Our results identify isoform-specific mitochondrial composition as a previously unrecognized determinant of regulated cell death and highlight COX4-1-driven mitochondrial remodeling as a potential mechanism of therapeutic resistance in glioblastoma."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • GPX4 • SLC7A11

ERM Inhibition Confers Ferroptosis Resistance through ROS-Induced NRF2 Signaling. (PubMed, Adv Sci (Weinh)) - "Here, ERM proteins are identified as modulators of erastin-induced ferroptosis...Notably, other pro-oxidants similarly attenuate ferroptosis at appropriate concentrations. Together, these results establish ERM proteins as regulators of ferroptosis and reveal an underappreciated group of ferroptosis inhibitors that engage ROS-NRF2-mediated redox-adaptation."

Journal • Fibrosarcoma • Oncology • Sarcoma • Solid Tumor • EZR • HMOX1 • KEAP1 • RDX

Targeting ferroptosis as a therapeutic vulnerability in preclinical models of cholangiocarcinoma (LCS 2026) - "Cells were treated with a ferroptosis inducer, erastin, a solute carrier family 7 member 11 (SLC7A11) inhibitor, to assess effects on colony formation, viability, proliferation, and mitochondrial respiration...These findings highlight ferroptosis modulation as a promising and targetable vulnerability in CCA, warranting further mechanistic and translational studies. (Supported by STSM CA22125, COST; 2023.01547.BD; PTDC/MED-FAR/3492/2021, FCT; LCF/PR/HR21/52410028, "la Caixa" Foundation)"

Preclinical • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • POU5F1 • SLC7A11 • SNAI1 • TWIST1

Temporal dynamics of ferroptosis markers and neuroprotective intervention in cerebral ischemia-reperfusion injury: Insights for therapeutic strategy development. (PubMed, Iran J Basic Med Sci) - "Additionally, CIRI mice received intraperitoneal injections of Ferrostain-1 (10 mg/kg/d) and Erastin (30 mg/kg/d)...This study elucidates the temporal dynamics of ferroptosis markers in the early stages of stroke, highlighting a therapeutic window for ferroptosis-related CIRI. These findings underscore the importance of targeting ferroptosis to improve neuronal survival and inform future CIRI therapies."

Journal • Cardiovascular • Ischemic stroke • Reperfusion Injury • GPX4

Ferroptosis induction enhances anti-PD-1 efficacy in NSCLC via HIF-1α/PD-L1 modulation. (PubMed, Transl Oncol) - "Ferroptosis inducers have dual effects in NSCLC, namely, promoting tumor cell death and triggering PD-L1-dependent immune evasion via the PI3K-AKT-HIF-1α pathway. However, combining ferroptosis inducers with anti-PD-1 antibodies retains the anti-tumor effect of ferroptosis and overcomes immune evasion by obstructing the PD-L1 pathway, offering a novel strategy for enhancing NSCLC immunotherapy efficacy."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • HIF1A • PD-L1

α-synuclein triggers NCOA4-FTH1-mediated ferroptosis of oligodendrocyte in multiple system atrophy. (PubMed, Acta Neuropathol) - "In MO3.13 cells, α-synuclein enhanced erastin-induced GPX4 loss, increased labile Fe2+ accumulation and aggravated mitochondrial depolarisation...Furthermore, the parallel reduction of circulating ODFC-EVs offers a readily accessible blood-based biomarker to discriminate MSA from PD. Together, these findings position the α-synuclein-NCOA4-FTH1 axis as a central pathogenic pathway and a compelling therapeutic target for MSA."

Journal • CNS Disorders • Hematological Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Solid Tumor • Targeted Protein Degradation • GPX4 • NCOA4

Ketogenic diet improves cognitive impairment in rats with temporal lobe epilepsy by activating the Nrf2/HO-1/GPX4 signaling axis to inhibit ferroptosis. (PubMed, Free Radic Biol Med) - "This research revealed that lithium-pilocarpine (LI-PILO)-induced status epilepticus in TLE models triggered pronounced ferroptosis in the rat hippocampus and that KDs inhibited neuronal ferroptosis in the hippocampus, as evidenced by elevated levels of the antioxidant factors, glutathione (GSH) and catalase (CAT), and decreased levels of 4-HNE, Fe2+ and the lipid peroxidation product malondialdehyde (MDA)...However, the neuroprotective effects of KDs were completely abolished by the ferroptosis inducer erastin...Western blot and qPCR results revealed that KDs activated the Nrf2/HO-1/GPX4 signaling axis and upregulated the expressions of Nrf2, HO-1, FTH1, xCT and GPX4. Our findings identify ferroptosis inhibition as a mechanism underlying the efficacy of KDs in epilepsy."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • CAT • GPX4 • KEAP1

PLA2R1-Mediated ERK-Dependent Ferroptosis: A Key Pathogenic Mechanism in Epileptic Neuronal Injury. (PubMed, Exp Cell Res) - "This study identified the PLA2R1-MEK-ERK-ferroptosis signaling axis, suggesting that PLA2R1 contributes to neuronal ferroptosis through ERK pathway activation in epilepsy. PLA2R1's druggability and ERK inhibitors' clinical safety provide foundation for therapeutic translation."

Journal • CNS Disorders • Epilepsy • ACSL4 • GPX4 • PACERR • PTGS2