elesclomol (STA-4783)

Dendritic SiO2 nanoparticles were sequentially loaded with elesclomol-copper complex (ESCu) and hemin, followed by hyaluronic acid (HA) coating to achieve CD44-mediated tumor targeting and HAase/pH-responsive drug release...In vivo results further demonstrated enhanced tumor accumulation, superior tumor growth inhibition, and favorable preliminary biosafety. This work provides a targeted nanotherapeutic strategy for enhanced cancer treatment through cuproptosis-photothermal combination therapy.

Notably, combining the SIRT5 inhibitor MC3482 with the cuproptosis inducer Elesclomol-Cu synergistically suppresses tumor growth in vivo, suggesting a promising therapeutic strategy. These findings elucidate mechanisms underlying cuproptosis resistance and propose a novel treatment approach for LUAD.

Elesclomol (15 nM) and copper chloride (CuCl₂, 10 µM) were used to induce cuproptosis, while DLAT overexpression and S6 kinase inhibition were used to clarify signaling processes. MELK expression was considerably elevated in DLBCL tissues and cell lines (P < 0.05)...On the other hand, MELK-mediated effects on cuproptosis and intracellular copper buildup were abolished by S6K suppression or DLAT overexpression. Through the PI3K/mTOR/S6K-DLAT axis, MELK imparts resistance to cuproptosis and increases DLBCL cell survival. MELK targeting may increase copper-induced cytotoxicity, offering a possible DLBCL treatment approach.

In this study, we investigated the therapeutic potential of combining Sunitinib with copper ionophore Elesclomol as a novel strategy against thyroid carcinoma. Clinically, TCGA analysis reveals SLC31A1 as a vulnerability in advanced thyroid cancer, with expression significantly downregulated in metastatic lesions, a deficit rescued by Sunitinib. Overall, these results demonstrate that Sunitinib and copper ionophores can induce synergistic cytotoxic effect, shedding light on therapeutic strategy for advanced thyroid carcinomas.

The cuproptosis pathway and its key protein SLC31A1 play a potential role in regulating GBM proliferation, migration, and TMZ sensitivity, and is closely associated with the tumor immune microenvironment, particularly macrophages. These findings may contribute to the selection of more effective clinical treatment strategies.

Herein, a carrier-free GSH-responsive in situ nanoreactor (TECJ) is fabricated, of which Cu ionophore elesclomol (ES), GSH-responsive nitric oxide (NO) donor O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1,2-diolate (JSK) and Cu2+ are integrated via self-assembly and coated with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)...Afterwards, the process above synergistically activates immunogenic cell death and cascades immunotherapy. Finally, TECJ successfully suppresses tumor growth and prevents tumor metastasis.

In patient-derived models, high HSF2/FDX1 expression predicts enhanced response to cuproptosis inducers. Our work establishes an epigenetic mechanism linking copper sensing to cuproptosis and nominates the CHD4/HSF2/FDX1 axis as potential biomarkers and therapeutic targets for precision oncology.

Furthermore, the cuproptosis activator elesclomol, inhibitor TTM, and Ras activator ML-098 were used...In vivo, 10 mg/kg Licochalcone A reduced tumor volume/weight by 42.27 ± 11.63%/45.13 ± 13.15%, with consistent protein changes (FDX1, LIAS, RAS, p-MEK and p-ERK). Collectively, it induces glioma cuproptosis via inactivating RAS/ERK, providing a potential therapeutic target.

We summarize opportunities and unresolved challenges in leveraging copper ionophores (e.g., elesclomol and disulfiram) and high-affinity chelators (e.g., tetrathiomolybdate) across malignant and non-neoplastic diseases. Furthermore, we address the translational challenges of precision delivery, including the use of nanoparticle-based systems to enhance therapeutic indices and the identification of biomarkers for patient stratification. By integrating recent pre-clinical and early clinical data (2023-2025), we suggest that targeting the mitochondrial-copper axis represents a promising, yet still experimentally grounded, avenue in precision medicine, while emphasizing current limitations in biomarker validation, delivery selectivity, and safety profiling.

CCNJL has the potential to act as a valuable prognostic indicator and immunotherapy target in CHOL. Its expression pattern and associations with clinical outcomes, immune characteristics, and drug sensitivity highlight its potential for improving diagnostic and therapeutic approaches. Future research should focus on elucidating the underlying mechanisms and validating these findings in larger cohorts.

The combination of elesclomol (a cuproptosis inducer) and selisistat (a SIRT1 inhibitor) effectively induced cuproptosis in CRC. Moreover, DLAT supplementation establishes a positive feedback loop that amplifies cuproptosis. These results underscore the critical role of nonhistone NAT10 lactylation in tumor cuproptosis and highlight the therapeutic potential of targeting this pathway for CRC treatment.

This resulted in intracellular Cu+ accumulation, triggering cuproptosis and excessive mitophagy, ultimately suppressing tumor growth. Therapeutically, the copper ionophore elesclomol potently inhibited tumor growth in a Thumpd1-knockout mouse model of LUAD.