elesclomol (STA-4783)

SLC7A11 knockdown regulates intracellular redox balance through the GSH-GPX4 axis, thereby promoting cellular cuproptosis. Targeting SLC7A11 can enhance the sensitivity of CRC cells to copper ionophores and may represent a novel therapeutic strategy to enhance cuproptosis of CRC cells.

In contrast, co-treatment with Cu and copper ionophore elesclomol (Cu-ES) triggered cuproptosis, a unique copper-dependent form of cell death, accompanied by mitochondrial dysfunction, dihydrolipoamide S-acetyltransferase aggregation, and ATP depletion. The PLK1 inhibitor BI-2536 recapitulated the effects of Cu-ES and exhibited synergistic activity when combined with Cu-ES, enhancing both cell death and EMT suppression. These findings highlight a novel regulatory mechanism of EMT through copper signaling and support copper-based combination therapies as a promising approach to simultaneously inhibit tumor growth and metastasis in colorectal cancer.

This inhibition collectively diminishes the expression and activity changes in complex IV, induces mitochondrial dysfunction, and promotes cuproptosis in ovarian cancer. This study further demonstrates that inhibiting the oxidative phosphorylation complex IV can enhance copper-induced cell death in ovarian cancer.

TERF2 knockdown induced apoptosis, suppressed cell proliferation, and downregulated the E2F pathway, while simultaneously enhancing cuproptosis susceptibility, as evidenced by reduced half-maximal inhibitory concentration (IC50) values of the elesclomol-copper (ES-Cu)...Downregulation of TERF2 inhibits the AML cell proliferation, induces apoptosis, and modulates cuproptosis sensitivity possibly via the E2F-mediated pathway. Targeting TERF2 not only inhibits proliferation but also unlocks cuproptosis as a therapeutic vulnerability, offering a potential strategy for AML.

Knockdown or pharmacological inhibition of METTL3 sensitized HCC cells to elesclomol-Cu-induced cuproptosis and effectively suppressed HCC xenograft growth in vivo. Clinically, elevated METTL3 expression was associated with poor HCC prognosis, and the protein expression of METTL3 and FDX1 was negatively correlated in HCC tissues. In conclusion, our findings identify an METTL3-mediated m6A regulatory mechanism controlling cuproptosis sensitivity, revealing METTL3 inhibition as a promising therapeutic strategy for HCC.

DACT1 promotes the malignant behavior of LSCC cells and suppresses cuproptosis by activating the PI3K/AKT signaling.

Combined treatment with an OGT inhibitor OSMI-1 and copper ionophore elesclomol eliminates tumor growth and remarkably enhances the sensitivity of tumor cells to cisplatin. Together, our study identifies TRIM21 Ubiquitinated-ALKBH5 as a critical gatekeeper to restrict cuproptosis, and such mechanism may contribute to tumor development and drug resistance in ESCC.

This study highlights the prognostic significance of lncRNAs associated with PCD in glioma and provides computational evidence for their potential as therapeutic targets. While the results suggest novel avenues for treatment development, they must be interpreted cautiously due to the lack of experimental validation. Future studies should aim to validate these results through controlled clinical trials and explore underlying molecular mechanisms.

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.

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.

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.

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.