Telomir-1：一种靶向衰老相关疾病和癌症的新型金属离子调节剂

Background: Telomir-1 is a first-in-class small-molecule metal modulator engineered to selectively regulate intracellular iron and copper homeostasis. It is being developed as a therapeutic candidate for aging-related diseases and cancer, leveraging a dual mechanism of action involving metal balance and epigenetic regulation. Rationale: Aggressive tumors-including triple-negative breast cancer and prostate cancer-often display an 'iron addiction' phenotype, characterized by excessive iron uptake, storage, and utilization to sustain rapid proliferation and survival. Telomir-1 targets this metabolic vulnerability by reducing the labile intracellular pools of iron and copper required for malignant cell growth, while sparing normal tissues. Mechanism of Action: Through coordinated modulation of metal-driven redox biology and chromatin-mediated gene control, Telomir-1 addresses two fundamental hallmarks of cancer: 1. Disrupted metal metabolism (iron/copper overload and oxidative stress) 2. Epigenetic repression of tumor-suppressor pathways This integrated mechanism positions Telomir-1 as a novel therapeutic strategy for malignancies driven by metal-dependent metabolic and epigenetic dysregulation. Molecular Insights: Many epigenetic enzymes-particularly iron- and copper-dependent histone demethylases (KDMs)-are overactive in aggressive cancers and require these metal cofactors for catalytic function. This creates a metabolic-epigenetic dependency, whereby malignant cells rely on elevated iron and copper to maintain an epigenetic state favorable to proliferation and survival. Telomir-1 precisely regulates labile metal pools, disrupting the activity of metal-dependent epigenetic enzymes and reactivating silenced tumor-suppressor programs, while simultaneously reducing oxidative stress and tumor metabolism. Conclusions: By bridging metal biology and chromatin control, Telomir-1 introduces a new therapeutic paradigm with potential applications in iron-dependent and epigenetically dysregulated cancers, including triple-negative breast cancer and prostate cancer, as well as broader aging-related pathologies.