elesclomol (STA-4783)

In this study, we demonstrate that IDH1-mutant AML cells are markedly more sensitive to cuproptosis induced by the copper ionophore elesclomol (ES), compared to their wild-type counterparts...In vivo experiments confirm that ES more effectively suppresses tumor growth in IDH1-mutant xenografts. These findings uncover a copper-dependent metabolic vulnerability and provide a rationale for exploiting cuproptosis as a therapeutic strategy in IDH1-mutant AML.

This study highlights FINs as effective cuproptosis potentiators and suggests a novel combinatorial regimen that simultaneously targets cuproptosis and ferroptosis, offering dual antitumor and bone-protective benefits for OS therapy.

For the cuproptosis, Rh1 promoted the elesclomol-Cu (ES-Cu) or disulfiram-Cu induced proliferation inhibition. Finally, this work verified that Ginsenoside Rh1 promoted the cuproptosis and repressed the immune evasion of GC cells. In short, Ginsenoside Rh1 attenuated the ATP7A to potentiate the copper accumulation and cuproptosis, thereby alleviating cuproptosis-related immune evasion.

Consequently, cells switch from the tricarboxylic acid (TCA) cycle respiration to glycolysis, reducing sensitivity to the copper ionophore elesclomol (ES)...HBx-mediated repression of SIRT3 disrupts STEAP4 deacetylation and mitochondrial targeting, fostering metabolic reprogramming and evasion of copper-induced cell death. The results provide a pre-clinical rationale for copper-directed combination strategies in HBV-associated HCC.

Using elesclomol-copper complex treatment, a cuproptosis model in HCT116 and RKO CRC cell lines was established...Tumors with elevated EZH2-NEAT1 expression may be particularly sensitive to copper-based therapies. This study establishes EZH2-NEAT1 expression as a potential biomarker for patient selection in cuproptosis-based cancer treatment, though the concurrent effects on tumor migration highlight complex therapeutic considerations for combination treatment strategies.

Keyword and co-citation analyses revealed a thematic shift from foundational mechanistic studies toward prognostic modeling, copper ionophore exploration (e.g., elesclomol and disulfiram), immune-related analyses, and bioinformatics-driven patient stratification. The strong geographic concentration of publications and limited international collaboration highlight structural imbalances in knowledge production and the need for broader global validation. This bibliometric mapping clarifies the field's early developmental stage and identifies priorities for future research, including cross-regional collaboration, experimental standardization, and cautious advancement toward clinical application.

Moreover, the combination of San with copper ionophores (Elesclomol-CuCl 2) exhibits synergistic effects in promoting cuproptosis...Surface plasmon resonance experiments and cellular thermal shift assay confirm that San strongly interacts with FDX1 and markedly enhances the thermostability of FDX1. In conclusion, our findings indicate that San substantially inhibits the progression of HCC by targeting FDX1/LIAS/DLAT/HSP70 axis-dependent cuproptosis.

Here, through a small-molecule compound screening, we identify elesclomol, a potent copper ionophore, which sensitizes BRCA-proficient ovarian cancer cells to PARPi by inhibiting activation of the ATR-CHK1 pathway...Importantly, we reveal a secondary metabolic vulnerability in PARPi-resistant ovarian cancer associated with de novo pyrimidine synthesis, suggesting that targeting this pathway as an effective strategy to eradicate drug-adaptive residual tumors and resistant patient-derived xenograft models following ATR and PARP co-inhibition. These findings propose de novo pyrimidine synthesis as an adaptive metabolic vulnerability that can be therapeutically targeted to overcome PARPi resistance in BRCA-proficient ovarian cancer.

In this study, elesclomol (ES) or disulfiram (DSF)/Cu was used to induce cuproptosis, and bathocuproine disulfonic acid (BCS) was used to inhibit it. In vivo, the role of the ALKBH5-ATOX1 axis in AML progression has also been confirmed. In Conclusion, The demethylase ALKBH5 downregulates ATOX1 by reducing its m⁶A levels, thereby modulating cuproptosis in AML-a mechanism that offers potential novel insights and therapeutic targets for AML treatment.

Next, two gastric cancer cell lines (AGS, HGC27) were selected for in vitro experiments to assess the combined effects of PUN and the copper ionophore elesclomol (ES) (hereafter referred to as ES-Cu, representing the combination of ES and Cu2+)...In combination therapy strategies, PUN can work synergistically with chemotherapy drugs to suppress gastric cancer growth. Furthermore, PUN enhances its inhibitory effect on gastric cancer by working synergistically with cuproptosis through targeting FDX1.

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.