ElesclomolSTA-4783AbMoleM2083是一种线粒体靶向小分子化合物核心机制在于作为铜离子载体Cu²⁺ ionophore与外源铜离子形成复合物Elesclomol-Cu将铜高效转运至线粒体基质触发铜依赖性细胞死亡铜死亡Cuproptosis。上述过程依赖于线粒体还原酶FDX1导致脂酰化蛋白如DLAT、DLST异常聚集、线粒体呼吸链功能障碍、活性氧ROS爆发性累积及ATP耗竭同时可协同诱导凋亡表现为Caspase-3/9活化、细胞色素c释放或铁死亡如在结直肠癌模型中通过ATP7A降解加剧化应激诱导铁死亡。在细胞实验中ElesclomolSTA-4783AbMoleM2083单用效果有限常需联合铜源如CuCl₂[1]。ElesclomolSTA-4783在KRAS突变人肺癌A549与Calu-1细胞中可抑制迁移并降低p-Erk水平[2]ElesclomolSTA-4783还在结直肠癌HCT116、LoVo细胞及癌症干细胞模型中联合CuCl₂ 处理后显著抑制克隆形成、降低铁硫簇蛋白并促进DLAT脂酰化累积在肝癌HepG2/PLC/PRF/5细胞中1–10 μM的 Elesclomol-Cu剂量依赖性抑制增殖伴随FDX1上调与DLAT寡聚化且可被铜螯合剂Ammonium tetrathiomolybdateTTM逆转。动物实验方面在裸鼠皮下移植A549异种移植模型中Elesclomol与Genipin 联用显著抑制肿瘤生长P0.008ElesclomolCAS No.488832-69-5在C57BL/6小鼠胶质母细胞瘤原位模型中联合TemozolomideTMZNSC 362856 增强抑瘤效果[3]在Menkes病模型mottled-brindled小鼠中Elesclomol递送铜离子至脑线粒体提升细胞色素c氧化酶水平并改善神经退行性表型[4]。参考文献及鸣谢[1] Yu, J.; Peng, Y.; Wang, K.; et al. The combination of elesclomol and Cu2 can inhibit the growth of colon cancer cells by targeting FDX1.2023.[2] Albayrak, G.; Korkmaz, F. D.; Tozcu, D.; et al. The outcomes of an impaired powerhouse in KRAS mutant lung adenocarcinoma cells by Elesclomol. Journal of cellular biochemistry2019, 120 (6), 10564-10571.[3] Buccarelli, M.; DAlessandris, Q. G.; Matarrese, P.; et al. Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth. Journal of experimental clinical cancer research : CR2021, 40 (1), 228.[4] Feng, Y.; Wu, J. J.; Sun, Z. L.; et al. Targeted apoptosis of myofibroblasts by elesclomol inhibits hypertrophic scar formation. EBioMedicine2020, 54, 102715.细胞实验参考细胞系AML cell方法Cells from each group were diluted to 5 × 104 cells/mL and 100 μL of cell suspension was added to a 96-well plate (control group: RPMI-1640 medium containing 40 nM Elesclomol (a copper ion inducer); experimental group: RPMI-1640 medium containing 40 nM Elesclomol and CuCl₂). The plate was pre-incubated in a cell culture incubator for 24 h (37 °C, 5% CO₂). Afterward, 10 μL of CCK-8 solution was added to each well, and the plate was incubated for an additional 2 h. Absorbance at 450 nm was measured using a microplate reader.浓度40 nM处理时间24 h.参考文献Discov Oncol. 2025 Jun 10;16(1):1044.* 上述方法来自公开文献仅供相同目的实验参考。如实验目的、材料、方法不同请参考其他文献。动物实验参考动物模型BALB/c nude mice配制PBS剂量10 mg/kg给药处理intraperitoneally administered参考文献Front Oncol. 2025 Jun 24;15:1584811.* 上述方法来自公开文献仅供相同目的实验参考。如实验目的、材料、方法不同请参考其他文献。体内实验的工作液建议现用现配当天使用如在配制过程中出现沉淀、析出现象可以通过超声和或加热的方式助溶。切勿一次性将产品全部溶解。建议制定动物给药及实验方案时尽量参考已发表的相关实验文献溶剂种类及配比众多简单地溶解目的化合物并不能解决动物给药依从性、体内生物利用度、组织分布等相关问题未必能保证目的化合物在动物体内充分发挥生物学效用。