elesclomol (STA-4783) / Madrigal Pharma - LARVOL DELTA

High FDX1 expression enhances the sensitivity of multiple myeloma cells to elesclomol (ASH 2025) - "Our findingsindicated that MM cells maintain low intracellular copper levels through expressing ATP7A in the cytoplasmic membrane. High FDX1 expression led to increased sensitivity of MM cells to elesclomol. Overall, this study reveals the copper metabolism characteristics of MM cells and provides a novel therapeutic strategy for the treatment of MM."

Hematological Malignancies • Multiple Myeloma • ATP7A • FDX1 • SDC1

Development and validation of a novel disulfidptosis-related gene signature for prediction of survival and immune microenvironment in osteosarcoma by WGCNA analysis. (PubMed, Discov Oncol) - "Besides, patients in the high-risk group exhibited lower IC50 values for vorinostat, elesclomol, OSI-906, pyrimethamine, thapsigargin, and doxorubicin, but a higher IC50 value for cisplatin, compared to those in the low-risk group, indicating differential drug sensitivities. In summary, we established a robust DRGs signature comprising BTN3A1, CEBPA, KCNAB2, TBX21, and MYC, which showed strong prognostic value and predictive potential for immune status and drug sensitivity in OS. Notably, functional experiments confirmed that BTN3A1 acted as a tumor suppressor in OS, highlighting it as a promising therapeutic target."

Gene Signature • IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • BTLA • BTN3A1 • CEBPA • LAG3 • PD-L1 • PD-L2 • TBX21

Elesclomol-Mediated Alterations of Liver Metabolism in the Context of Mouse Mblac1 Disruption. (PubMed, Annu Int Conf IEEE Eng Med Biol Soc) - "Mblac1 KO mice injected with ES demonstrated a significant increase of 33.72% in liver RR values versus WT mice injected with vehicle, amounting to a 47.29% recovery of RR . Our findings support the requirement of MBLAC1 protein to regulate in vivo mitochondrial function via maintenance of Cu(I) homeostasis and the demonstration of a potential therapeutic route for treatment of individuals with MBLAC1 deficiency."

Journal • Preclinical

SNHG26 Promotes Colorectal Cancer Progression via CDKN2A-Dependent Regulation of Cuproptosis and CD8+ T Cell-Mediated Immunity. (PubMed, J Cell Mol Med) - "The effects of the SNHG26-CDKN2A axis on Cu + ELES(copper plus elesclomol)-induced cuproptosis and CD8+ T cell-mediated anti-tumour immunity were evaluated through cell viability, apoptosis, co-culture cytotoxicity and migration assays...Our findings reveal a novel regulatory axis whereby SNHG26 promotes CRC progression by destabilising CDKN2A mRNA, resulting in enhanced cell proliferation, cuproptosis and immune evasion. This study provides new insights into the molecular mechanisms underlying CRC development."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CDKN2A • CXCL10 • CXCL9

Metformin Inhibits Microglial Activation-Mediated Cuproptosis by Modulating the TLR4/Myd88/NF-κB Signaling Pathway in Parkinson's Disease. (PubMed, Mol Neurobiol) - "Notably, the neuroprotective effects of Met were partially reversed by elesclomol (ELC), a known cuproptosis inducer. This study demonstrated that Met inhibits microglial activation-mediated cuproptosis by modulating the TLR4/Myd88/NF-κB signal pathway in PD murine/cell models, thus exerting neuroprotective effects. These findings therefore suggest that Met may serve as a promising therapeutic agent for preventing DA neuron degeneration in PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • FDX1 • MYD88 • SLC31A1 • TLR4

Adenylosuccinate lyase (ADSL) is a pan-cancer prognostic and immune biomarker with distinct roles in hepatocellular carcinoma. (PubMed, Discov Oncol) - "ADSL holds potential as a promising prognostic marker for OS in various cancer types, particularly in HCC. Additional research is needed to confirm these findings and to understand how ADSL affects cancer development."

Biomarker • Journal • Pan tumor • Hepatocellular Cancer • Oncology • Solid Tumor

Elesclomol-Induced Copper Influx Attenuates Lung Adenocarcinoma Progression With Involvement of the ER Stress/PCK2 Axis. (PubMed, FASEB J) - "In vivo experiments revealed that ES inhibited tumor growth and upregulated PCK2. Taking together, our findings reveal that the ES-ER stress-PCK2 axis is a critical mediator of copper-induced metabolic disruption, providing a rationale for targeting cuproptosis pathways in LUAD therapy."

Journal • Lung Adenocarcinoma • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PCK2

Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in multiple myeloma. (PubMed, Transl Oncol) - "In vitro experiments, the combination of elesclomol (a copper ion carrier) and bortezomib (Bortezomib) demonstrated a synergistic anti-myeloma effect through excessive intracellular reactive oxygen species generation. This study provides valuable insights into the role of CRGs in MM, potentially aiding in prognosis prediction and the development of effective, personalized therapeutic strategies."

Biomarker • Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • ATP7B • CDC37 • CDKN2A • CKS2 • DLAT • HSP90AB1 • MELTF • PDHA1 • VCAM1

Uncovering the Critical Role of Cuproptosis in Wilson Disease: Insights Into Potential Therapeutic Targets. (PubMed, J Cell Mol Med) - "Copper exposure decreased cell viability and increased LDH release, exacerbated by Elesclomol and alleviated by Tetrathiomolybdate...Key mediators identified include Gpc1, Gls, Lox and App, which were validated as potential therapeutic targets. These findings provide new insights into the molecular mechanisms underlying WD and may inform the development of targeted treatment strategies."

Biomarker • Journal • Gene Therapies • Genetic Disorders • Hepatology • Liver Failure • Metabolic Disorders • Movement Disorders • ATP7B • DLAT • FDX1 • GPC1 • LIAS

Chromosome 15q15 Deletion Drives Brain Metastasis in Non-Small Cell Lung Cancer. (PubMed, J Thorac Oncol) - "The 15q15 deletion promotes BM development through aberrant MYC signaling and the subsequent reprogramming of carbohydrate metabolism."

Journal • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MGA

METAL REGULATORY TRANSCRIPTION FACTOR-1 (MTF-1) DRIVES CERVICAL CANCER PROGRESSION BY SUPPRESSING CUPROPTOSIS VIA TKT-MEDIATED METABOLIC AND REDOX REPROGRAMMING (IPVC 2025) - "Cuproptosis was induced using the copper ionophore Elesclomol (ES) combined with CuCl₂, with intracellular Cu²⁺ levels, mitochondrial membrane potential (JC-1), reactive oxygen species (ROS), and key cuproptosis markers (FDX1, Lip-DLAT, DLAT oligomers) quantified... MTF-1 drives cervical cancer progression by suppressing cuproptosis through TKT-mediated metabolic reprogramming and redox balance, highlighting its potential as a therapeutic target."

Cervical Cancer • Oncology • Solid Tumor • DLAT • FDX1

Prognostic evaluation and experimental validation of cuproptosis-related hub genes identified through weighted gene co-expression network analysis in uveal melanoma. (PubMed, Cancer Cell Int) - "Compared to several previous studies, we have extended the search for CRGs very rigorously in order to increase the value of cuproptosis in the prognosis and treatment of UVM. This whole transcriptome analysis elucidates the crucial role of cuproptosis-related molecular subtypes in the prognosis of UVM, highlights its association with the TME, and provides a scientific basis for clinical drug decisions."

IO biomarker • Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Electromagnetic Wireless Remote Control of Reprogramming Immune Dysfunction via N-Doped Carbon Dots-Mesoporous Silica-Mediated Cuproptosis and Dendritic Cell Retention. (PubMed, Adv Healthc Mater) - "To overcome this, a pH-responsive lung-metastasis-targeted wirelessly charging-boosted dual-catalyst nanoplatform composed of tumor-penetrating solid lipids/polymer-coated N-doped carbon dots/mesoporous silica nanoparticles (CMS), loaded with cuproptosis-inducing agents (elesclomol-copper, EsCu) is developed for initiating a self-cascade immune response and dendritic cell retention...This cytotoxicity is paired with in situ antigen release, which CMS carriers deliver to reprogram DCs, initiating sustained immune activation. When combined with immune checkpoint blockade (anti-PD-1), the CMS system effectively suppresses lung metastases and extends survival beyond 60 days."

Journal • Oncology

Mitochondria-transliterated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy. (PubMed, Cell Death Differ) - "Furthermore, our results demonstrated that the combination of Elesclomol with HSP90 inhibitor Ganetespib exhibited synergistic anti-tumor effects. In conclusion, our findings that mitochondria-translocated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy can provide critical insights into developing effective pro-oxidative therapies against tumors."

Journal • Oncology • CDC37 • LONP1 • TFAM

Comprehensive investigation of cuproptosis-related genes in clinical features, biological characteristics, and immune microenvironment in B-cell Non-Hodgkin lymphoma. (PubMed, J Transl Int Med) - "Moreover, we combined elesclomol and doxorubicin in our in vitro experiments and found synergetic antitumor effects of the two agents, and the underlying mechanism is the overgeneration of intracellular Reactive Oxygen Species (ROS). We demonstrated the important value of CRG signatures in prognosis of B-cell NHL patients, and that may be a potential antitumor target for B-cell NHL."

Journal • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Targeting Mitochondrial Oxidative Stress by Calcium/Copper/Elesclomol Tri-Overloaded Nanocages for Osteosarcoma Immunotherapy via Immunogenic Cell Death. (PubMed, ACS Nano) - "Finally, overexpression of CRT and NLRP3 activates the DCs-CD8+ T cell immune response axis through the lymphocyte-mediated immunity pathway, enabling effective immunotherapy. Considering the in vivo pH-responsive biodegradability in the tumor immune microenvironment (TIME), our study has provided an impetus for the design and preparation of copper-based nanomaterials, which are efficacious in OS immunotherapy."

IO biomarker • Journal • Metabolic Disorders • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • ATP7A • CD8 • MTAP • NLRP3

Real-time nanomechanical visualization and profiling for rapid discrimination of early-stage regulated cell death modalities. (PubMed, Talanta) - "Real-time TFM-CRIM monitoring revealed unique kinetic signatures discriminating RCD modalities: staurosporine-induced apoptosis exhibited an extremely rapid force collapse to near-zero by ∼20-30 min (initiating within 10 min); Elesclomol-CuCl2-induced cuproptosis displayed a swift, sustained force decrease from ∼10 to 20 min, stabilizing at a low level by ∼40-60 min. These profiles were markedly different from the slower ferroptosis kinetics: RSL3-induction initiated a sustained force reduction ∼20-40 min (over ∼3 h), while Erastin-induction, after an early subtle decrease from ∼20 min, showed a delayed major decline from ∼120 min (spanning ∼6 h)...These distinct nanomechanical signatures, correlated with alterations in cytoskeletal actin fibres, enable robust RCD classification. This work establishes TFM-CRIM-based nanomechanical profiling as a rapid, quantitative, and highly sensitive analytical method for early RCD..."

Journal

PD-L1 nanobody-engineered bacterial outer membrane vesicles delivering cuproptosis micelles for potentiated cancer immunotherapy. (PubMed, Biomater Adv) - "Here, we fabricated a PD-L1 nanobody-engineered bacterial outer membrane vesicles (OMVs) delivering elesclomol (ES) micelles for enhanced immunotherapy in triple-negative breast cancer (TNBC)...Notably, our nanoparticles elicited a robust antitumor immune response with increased infiltration and activation of CD8+ T cells and Treg depletion. By integrating cuproptotic tumor death with immune checkpoint blockade, the dual-functional nanoplatform represents a promising strategy for potentiated immunotherapy."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • PD-L1

Investigation of the Putative Relationship Between Copper Transport and the Anticancer Activity of Cisplatin in Ductal Pancreatic Adenocarcinoma. (PubMed, Cells) - "Two major strategies were pursued: (i) inhibiting copper transporters ATP7A and B with tranilast (TR) and omeprazole (OM) to block the cellular copper and, potentially, also cisplatin efflux, and (ii) using the chelator elesclomol (ES) to elevate intracellular copper and cisplatin levels. Moreover, all drugs contributed to the enhanced cellular anticancer activity of cisplatin, with ES being the most effective compound. The results suggest that the targeted modulation of copper transport mechanisms may offer novel adjuvant approaches for the treatment of PDAC."

Journal • Hepatocellular Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ATP7A

Cuproptosis in osteoarthritis: Exploring chondrocyte cuproptosis and therapeutic avenues. (PubMed, J Orthop Translat) - "In vitro, we used elesclomol and copper sulfate to create a cuproptosis model in mouse chondrocytes...Chondrocyte cuproptosis plays a key role in the occurrence and development of knee osteoarthritis. The copper ion chelator (Tetrathiomolybdate) has been proved to be able to treat knee osteoarthritis by alleviating chondrocyte cuproptosis."

Journal • Immunology • Metabolic Disorders • Osteoarthritis • Pain • Rheumatology • DLAT • FDX1

UNCOVERING THE CRITICAL ROLE OF CUPROPTOSIS IN WILSON DISEASE: IDENTIFICATION OF DIAGNOSTIC BIOMARKERS AND THERAPEUTIC TARGETS (AASLD 2025) - "Copper exposure decreased cell viability and increased LDH release—exacerbated by Elesclomol and alleviated by Tetrathiomolybdate... Cuproptosis contributes significantly to copper-induced liver injury in WD. Key mediators include Lox, Afp, Alb, Gpc1, Gls, and App, with Afp and Alb showing potential as diagnostic biomarkers. These findings offer new insights into WD pathogenesis and potential therapeutic targets."

Biomarker • Genetic Disorders • Hepatitis B • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Liver Failure • Metabolic Disorders • Movement Disorders • AFP • ATP7B • DLAT • FDX1 • GPC1 • LIAS

Efficient copper ion transport triggers in situ photothermia and cuproptosis for boosting colon cancer immunotherapy. (PubMed, Biomaterials) - "Moreover, the degraded nanoplatform in acidic microenvironment released the copper ionophores elesclomol to accelerate the transport and accumulation of copper ions at mitochondria for inducing the PTT-promoted cuproptosis. The combined cuproptosis and PTT induced immunogenic cell death, activated the robust immune response and reprogrammed the immunosuppressive tumor microenvironment, demonstrating potent efficacy in inhibiting tumor proliferation and recurrence. Collectively, this study developed an efficient copper ion transport nanoplatform with integrated functions as cuproptosis and in situ endogenous H2S-triggered PTT for boosting colon cancer immunotherapy."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

YAP Expression Confers Therapeutic Vulnerability to Cuproptosis in Breast Cancer Cells by Regulating Copper Homeostasis. (PubMed, Adv Healthc Mater) - "Furthermore, a copper-based functional nanomaterial, EsMP@Fu is developed, which incorporates melatonin and the cuproptosis inducer elesclomol complex with copper ions (Cu(II)) (Es:Cu)...In vivo study demonstrated that EsMP@Fu significantly suppressed tumor growth by 60%, with more pronounced effects on distant metastasis and the induction of antitumor immunity. Collectively, the findings demonstrate that YAP overexpression confers sensitivity and therapeutic vulnerability to cuproptosis induction, presenting a promising strategy for precision medicine through tailored copper-based therapy."

Journal • Breast Cancer • Oncology • Solid Tumor

Targeting FDX1 with Icaritin Attenuates Neuronal Cuproptosis by Reconciling Mitochondrial Fission-Fusion Dynamics and Bioenergetic Homeostasis. (PubMed, Free Radic Biol Med) - "Thus, this study was aimed to investigate ICT's protective mechanisms against cuproptosis induced by the cupric sulfate and copper ionophore elesclomol (Cu-ES) in HT22 hippocampal neuronal cells. Furthermore, ICT rescued mitochondrial dynamics by promoting fusion and inhibiting fission. Our findings demonstrate ICT is a potent inhibitor of neuronal cuproptosis, targeting FDX1 to alleviate mitochondrial oxidative stress, dysfunction, and dynamics disorder, presenting a promising therapeutic strategy."

Journal • Metabolic Disorders • ATP7B • DLAT • FDX1 • SLC31A1

Tumor-responsive cuproptosis nanoinducer realizing efficient PANoptosis for enhanced cancer immunotherapy. (PubMed, Theranostics) - " We engineered Elesclomol-Cu@PDPA nanoparticles (PEC NPs) designed to induce cuproptosis and subsequent PANoptosis... This study provides a robust strategy utilizing PEC NPs to induce efficient cuproptosis and PANoptosis for enhanced immunotherapy. It offers new insights into boosting tumor immunogenicity through the activation of multiple RCDs pathways."

Journal • Oncology