Copper Transporter 1‑Mediated Deregulation of Copper Homeostasis Impacts MYC and Oxidative Phosphorylation Pathways and Increases the Sensitivity of Tumor Cells to Complex I Inhibitors.
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Trace Elements in Health
Ferroptosis and cancer prognosis
Metal complexes synthesis and properties
Certain tumors are dependent on copper for proliferation, metastasis, and energy production, making them particularly susceptible to copper depletion.
APA
Rima Mouawad, Nada H. Eisa, et al. (2026). Copper Transporter 1‑Mediated Deregulation of Copper Homeostasis Impacts MYC and Oxidative Phosphorylation Pathways and Increases the Sensitivity of Tumor Cells to Complex I Inhibitors.. ACS pharmacology & translational science, 9(4), 902-924. https://doi.org/10.1021/acsptsci.5c00651
MLA
Rima Mouawad, et al.. "Copper Transporter 1‑Mediated Deregulation of Copper Homeostasis Impacts MYC and Oxidative Phosphorylation Pathways and Increases the Sensitivity of Tumor Cells to Complex I Inhibitors.." ACS pharmacology & translational science, vol. 9, no. 4, 2026, pp. 902-924.
PMID
41988364 ↗
Abstract 한글 요약
Certain tumors are dependent on copper for proliferation, metastasis, and energy production, making them particularly susceptible to copper depletion. Altering copper homeostasis has emerged as a promising strategy for treating these cancers. Previously, we synthesized novel compounds, JR4-187 (JR4) and JR5-26B (JR5), which demonstrated copper-dependent in vivo efficacy. RNA-seq analysis revealed that JR4 treatment in colon cancer cells leads to a marked downregulation of oxidative phosphorylation and MYC-targeted genes. Both JR4 and JR5 reduce MYC and NDUFS7 protein levels. Additionally, JR4 and JR5 increase tumor cell sensitivity to complex I inhibitors, including AGB-374, a novel NDUFS7 inhibitor that we developed. AGB-374 exhibited in vivo efficacy when administered orally, both as a single agent and in combination with JR5, in a mouse model of colon cancer. Our findings indicate a significant functional relationship between CTR1 and NDUFS7, providing a foundation for the development of new cancer therapies.
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