disulfiram / Generic mfg. - LARVOL DELTA

Exploration of the role of macrophage mitochondrial damage-mediated excessive pyroptosis in ITP (ASH 2025) - "A passive ITP mouse model was established, and both pyroptosis inhibitor disulfiram and Mdivi-1were used for intervention to evaluate changes in mitochondrial function, pyroptotic products, andplatelet levels...Conclusions Mitochondrial damage induces excessive pyroptosis in macrophages through the classical pyroptosispathway mediated by NLRP3/Caspase-1, thereby contributing to the pathogenesis of ITP. Thispathological process holds promise as a potential target for ITP intervention."

Inflammation • HMGB1 • IL18 • IL1B • NLRP3

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

Targeting gasdermin D-mediated pyroptosis: a precision anti-inflammatory strategy for acute and chronic lung diseases. (PubMed, Inflammopharmacology) - "In addition, we performed a systematic evaluation of emerging therapeutic interventions such as direct pore formation inhibitors (disulfiram and necrosulfonamide), upstream caspase inhibitors (VX-765), and anti-inflammatory phytochemicals (andrographolide, emodin, and baicalin). This review reports that GSDMD is a promising therapeutic target for acute and chronic inflammatory lung disease. This study provides new mechanistic contributions and translational approaches to augment targeted anti-inflammatory interventions in respiratory care by precise pyroptosis modulation."

Journal • Review • Acute Respiratory Distress Syndrome • Asthma • Chronic Obstructive Pulmonary Disease • Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CASP4 • IL18 • IL1B

Andrographolide-induced PANoptosis underlies its multiple organ toxicity in mice. (PubMed, Toxicol Appl Pharmacol) - "Consistent with this, Andro induced lytic cell death was markedly attenuated by caspase-1 inhibitor VX-765, pan-caspase inhibitors (IDN-6556, Z-VAD-FMK) and GSDMD/E inhibitor (disulfiram). In addition, RIPK1 inhibition (by Nec-1) partially reduced cell death, confirming RIPK1-dependent necroptosis as a minor contributor. In conclusion, our data establish PANoptosis as an important mechanism of Andro-induced organ injury, providing a mechanistic framework for Andro's dichotomous bioactivity, informing evidence-based dosing strategies to maximize therapeutic efficacy while mitigating toxicity risks in clinical practice."

Journal • Preclinical • CASP8 • GSDME • RIPK1

Revisiting the Disulfiram-Like Reaction Between Alcohol and Oral Metronidazole. (PubMed, Sex Transm Dis) - "While all four case reports and one older clinical trial reported a potential link between some oral 5-nitroimidazoles and DLR, 3 clinical trials, one cross-sectional chart review, and 2 experimental animal studies did not. Thus, the available evidence does not strongly support a clinically significant interaction between alcohol and oral MTZ, calling into question the need for strict alcohol abstinence during treatment."

Journal • Cardiovascular

A powerful agonist for metal ion interference therapy: Multiple programs of cell death to amplify tumor metalloimmunotherapy. (PubMed, Biomaterials) - "Herein, a novel MIIT initiator, layered double hydroxides composite, disulfiram (DSF)-loaded ZnCuAl-LDH, was constructed to efficiently co-deliver multiple metal ions and enhance the retention ability of metal ions within the cells...Therefore, ZCA-LDH@DSF demonstrated a remarkable ability to induce MIIT, thereby triggering multiple programs of cell death and inhibiting tumor growth and metastasis. Overall, the good biological safety and application prospect of ZCA-LDH@DSF initiator provide a new treatment model for combating tumor."

IO biomarker • Journal • Oncology • ATP7A • ATP7B

Citrinin induces renal PANoptosis by mediating mitochondrial dysfunction through the GSDMD-N/DRP1 pathway. (PubMed, J Hazard Mater) - "Notably, disulfiram, a GSDMD-N inhibitor, also mitigated mitochondrial dysfunction and PANoptotic responses through the DRP1 pathway. Molecular docking and Co-IP assays confirmed a direct interaction between GSDMD-N and DRP1. Collectively, these findings reveal that CTN induces PANoptosis through GSDMD-N/DRP1-mediated mitochondrial dysfunction, offering new mechanistic insights into CTN-induced nephrotoxicity and highlighting potential therapeutic targets for mitigating mycotoxin-associated kidney injury."

Journal • Metabolic Disorders • Renal Disease

GSDMD deficiency attenuates BPD by suppressing macrophage pyroptosis and promoting M2 polarization. (PubMed, Cell Death Discov) - "Using neonatal C57BL/6 wild-type (WT) and GSDMD-knockout (GSDMD-/-) mice, we established a hyperoxia-induced BPD model (85% FiO₂, 14 days) and administered the GSDMD inhibitor disulfiram (50 mg kg⁻¹ intraperitoneally, once daily for 7 days)...Collectively, these findings identify GSDMD-mediated macrophage pyroptosis as a critical driver of BPD-related lung injury. Targeted GSDMD inhibition, whether genetic or pharmacologic, alleviates experimental BPD by down-regulating IL-1β and promoting alveolar development, thereby providing a promising therapeutic avenue for this devastating neonatal disorder."

Journal • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases • IL1B

Evogliptin prevents ceramide-induced pyroptosis during calcification via modulation of NLRP3/GSDM-D mediated pathway in Vascular Smooth Muscle Cells. (PubMed, PLoS One) - "Furthermore, MCC950 (NLRP3 inhibitor), disulfiram (GSDM-D inhibitor) and evogliptin significantly downregulated osteogenic and pyroptotic markers including LDH release in both Pi-induced only and CER + Pi-treated VSMCs. Also, the cleavage efficiency of GSDM-D was high in Pi and CER + Pi groups which was reduced with prior treatment of evogliptin. Hence, our data demonstrate that evogliptin alleviates VC by blocking phenotypic transition and associated pyroptosis via modulation of NLRP3/GSDM-D mediated pathway in CER-induced VSMCs."

Journal • Cardiovascular • Inflammation • BMP2 • IL18 • IL1B • NLRP3 • RUNX2

Novel Promising Therapeutic Strategies for Advancing the Treatment of KMT2A-Rearranged AML (ASH 2024) - "We selected Asparaginase (ASPN), IACS-010759 (IACS), Disulfiram, Gallein, 5-Azacytidine, Quizartinib, Trametinib, γ-Secretase inhibitor and ICG-001 to be tested either alone or in combination with Venetoclax (VEN) in 3D with ex vivo AML cells and AML patient derived MSCs. We support the use of pediatric AML-PDXs in preclinical testing for their ability to mimic the heterogeneity of drug response, aiding in the identification of tailored second-line treatments. VEN+ASPN combination represents a novel promising therapeutic strategy for advancing the treatment of KMT2A-rearranged AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CREBBP • CTNNB1 • FAT1 • FLT3 • KDM5A • KMT2A • NOTCH1 • NRAS • TET2

Multi-omic integration reveals intra-tumour heterogeneity and identifies disulfiram and copper as a synergistic therapy in paediatric ependymoma (SNO 2025) - "This is the first instance where multi-omic data integration and intra-tumor heterogeneity have been investigated for paediatric EPN, revealing novel therapeutic targets in the context of gene-metabolite correlations. In-vivo efficacy studies using the MAF-928 model are currently ongoing."

Heterogeneity • Brain Cancer • Ependymoma • Oncology • Pediatrics • Solid Tumor

Repurposing Disulfiram in a Promising Combination Therapy for Cryptosporidiosis in Immunocompromised Mice. (PubMed, Acta Trop) - "Nitazoxanide (NTZ) is currently the only FDA-approved drug for cryptosporidiosis, yet its efficacy is significantly reduced in immunosuppressed hosts. Transmission electron microscopy confirmed full epithelial regeneration only in the dual therapy group, with intact microvilli, normal mitochondria, and restored cellular junctions. In conclusion, disulfiram, particularly when combined with NTZ, demonstrated enhanced anti-cryptosporidial efficacy and may serve as a promising adjunct therapy, mostly for immunocompromised patients."

Journal • Preclinical • Infectious Disease

Multifunctional DSF-loaded ICG-chelated nanozyme for four-in-one enhanced synergistic tumor therapy. (PubMed, Mater Today Bio) - "Addressing these limitations, we developed an innovative "4-in-1" strategy utilizing Disulfiram (DSF)-loaded Fe-based near-infrared-triggered DMTICH nanozymes integrating synergistic chemotherapy, chemodynamic therapy, photothermal therapy, and photodynamic therapy...The potent anticancer capability of DMTICH was also validated in animal studies, where it elevated the tumor site temperature to ∼58.3 °C and reduced tumor size to 12.6 % of that in the control group after a complete treatment period. This innovative approach highlights a promising synergistic "4-in-1" strategy, offering a powerful enzymatic platform for multimodal cancer therapies."

Journal • Oncology • CAT

Connection between granulosa cell pyroptosis and oocyte endoplasmic reticulum stress in a mouse model of polycystic ovary syndrome. (PubMed, J Ovarian Res) - "High androgen induced pyroptosis of ovarian granulosa cells in a mouse model of PCOS, leading to ER stress in oocytes and a decrease of the oocyte maturation rate. Effective alleviation of granulosa cell pyroptosis can inhibit ER stress in oocytes and improve their maturation rate. This study provides new therapeutic targets for improving oocyte maturation in PCOS."

Journal • Preclinical • Polycystic Ovary Syndrome • CASP1

Copper-cysteamine nanoparticles in cancer treatment: a systematic review. (PubMed, Cell Biol Toxicol) - "Across these studies, Cu-Cy NPs consistently suppressed tumor growth and triggered cancer cell death by generating reactive oxygen species (ROS) and enhanced therapeutic effects when combined with co-treatments such as disulfiram, potassium iodide, and other adjunct therapies...These findings underscore the nanoparticles' potential to transform current oncology strategies, offering targeted, versatile, and personalized therapeutic options. Continued investigation is essential to fully elucidate their mechanisms, optimize treatment protocols, and translate these promising preclinical results into safe and effective clinical applications."

Journal • Review • Oncology

Novel Disulfiram-Loaded Metal-Organic Nanoparticles Inhibit Tumor Growth and Induce Immunogenic Cell Death of Triple-Negative Breast Cancer Cells. (PubMed, Pharmaceutics) - "In a 4T1 TNBC mouse model, systemic [Cu(DDC)2] NP treatment significantly inhibited tumor growth without combinational chemo- or radiotherapy. This DSF-based metal-organic NP integrates drug repurposing, immune activation, and tumor microenvironment remodeling into a single platform, offering strong translational potential for treating aggressive breast cancers."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CALR • HER-2 • MMP3 • MMP9 • VIM

Drug Repurposing in Veterinary Oncology: Myth or Reality? (PubMed, Vet Sci) - "The therapeutic agents discussed include non-steroidal anti-inflammatory drugs (e.g., piroxicam), metabolic modulators (e.g., metformin), anti-parasitic drugs (e.g., fenbendazole), immunomodulators (e.g., thalidomide, oclacitinib), cardiovascular agents (e.g., propranolol, statins, losartan), and other compounds such as auranofin and disulfiram. Challenges to clinical implementation, including limited funding, regulatory and ethical considerations, and the need for well-designed, multi-institutional clinical trials, are discussed. Ultimately, drug repurposing represents a practical and translationally valuable approach to broaden therapeutic options, improve quality of life in companion animals, and advance comparative oncology by promoting progress that benefits both veterinary and human patients."

Journal • Review • Cardiovascular • Oncology

Disulfiram inhibits Gasdermin D pores formation and improves insulin-dependent glucose uptake and glucose homeostasis in skeletal muscle of obesity-induced insulin-resistant mice. (PubMed, Sci Rep) - "Moreover, DSF reduced GSDMD-NT oligomerization and IL-1β release in the gastrocnemius muscle. These findings suggest a novel pathogenic role for GSDMD in skeletal muscle IR and support DSF as a potential candidate for metabolic disease intervention."

Journal • Preclinical • Diabetes • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • IL1B • NLRP3

ALDH1A inhibitors: Research advances in cancer therapeutics. (PubMed, Eur J Med Chem) - "In recent years, research groups have developed a series of highly selective and potent ALDH1A inhibitors (e.g., coumarin-based compounds, disulfiram derivatives)...This review summarizes the applications and recent advances of the ALDH1A family in the treatment of various cancers, with a particular focus on the structural optimization and structure-activity relationships (SAR) of small-molecule inhibitors, their mechanisms of action and future development directions. This work is significant for facilitating the clinical translation of novel small-molecule inhibitors and for improving strategies to overcome drug resistance."

Journal • Review • CNS Disorders • Metabolic Disorders • Oncology

Recent advances in the study of cuproptosis in gliomas. (PubMed, Int Immunopharmacol) - "Copper chelators, such as trientine and disulfiram, can regulate intracellular copper levels and induce glioma cell death, thereby enhancing the efficacy of chemotherapy. However, the specific mechanisms of cuproptosis and its clinical application in glioma treatment require further exploration. This field of study promises to offer novel insights and directions for developing more effective glioma therapies."

Journal • Review • Brain Cancer • Glioma • Oncology • Solid Tumor • FDX1 • LIAS

Multi-omic integration reveals intra-tumour heterogeneity and identifies disulfiram and copper as a synergistic therapy in paediatric ependymoma (WFNOS 2025) - "This is the first instance where multi-omic data integration and intra-tumor heterogeneity have been investigated for paediatric EPN, revealing novel therapeutic targets in the context of gene-metabolite correlations. In-vivo efficacy studies using the MAF-928 model are currently ongoing."

Heterogeneity • Brain Cancer • Ependymoma • Pediatrics • Solid Tumor

The Course of Neuroendocrine Healing With Abstinence In ICD-11 Alcohol Dependence (Neuroscience 2025) - " To test whether neuro-endocrine healing occurs in frequent, heavy drinkers, this study 1) compared heavy drinking AlcD test subjects (n=16) with light drinking control subjects (n=15) at baseline and then 2) assessed the test subjects prospectively at three, and six months of supervised, disulfiram assisted abstinence... These data indicate that neuro-endocrine healing occurs with abstinence but is gradual. Healing may take up to six months to reach its full potential. This suggests the possibility that 1) neuro-endocrine effects may impair complex cognition and decision making early in the healing course and 2) neuro-endocrine healing late in the course may account for the often unrealistic sense of well-being that occasions alcohol relapse."

Addiction (Opioid and Alcohol) • CNS Disorders

Cuproptosis-driven astrocyte reactivity exacerbates experimental cerebral malaria pathogenesis. (PubMed, Parasit Vectors) - "These findings establish that cuproptosis exacerbates ECM pathogenesis by promoting astrocyte reactivity, highlighting copper homeostasis modulation as a potential therapeutic strategy for CM."

Journal • Infectious Disease • Malaria • Oncology • ATP7A • CXCL10 • DLAT • DLST • FDX1 • GFAP • IL6 • SLC31A1 • TNFA

Inranasal administration of disulfiram in rats produces rapid and potent anxiolytic-like effects without adverse alcohol-related interactions (Neuroscience 2025) - "Direct and efficient nose-to-brain delivery likely underlies the rapid onset and reduced systemic toxicity. Collectively, the results highlight the therapeutic potential of DSF beyond its conventional use, providing compelling preclinical evidence that intranasal delivery may represent a novel, safe, non-invasive, and fast-acting anxiolytic strategy."

Late-breaking abstract • Preclinical • CNS Disorders • Mood Disorders • Psychiatry • CCR2

Exosome-camouflaged inhalable (PDSA-HSA) nanocarrier for targeted disulfiram delivery in lung cancer therapy. (PubMed, Biomater Adv) - "The inhalable Exo@(PDSA-HSA/DSF) formulation effectively inhibited tumor growth and prolonged survival in a LC animal model with negligible systemic toxicity. Overall, this exosome-camouflaged PDSA-HSA nanocarriers as an effective platform a promising strategy for targeted inhalation therapy in LC, integrating enhanced drug delivery, tumor efficacy, and excellent biocompatibility."

Journal • Lung Cancer • Oncology • Solid Tumor