Ammonium tetrathiomolybdateTTMAbMole, M54856作为一种多功能无机钼硫化合物在基础科研中展现出多重应用。Ammonium tetrathiomolybdate能螯合铜离子[1]干扰铜依赖性通路如抑制ATP7B铜转运蛋白表达、降低赖氨酰氧化酶活性及胶原交联并抑制铜死亡Ammonium tetrathiomolybdateTTMCAS No.15060-55-6同时也能作为硫化氢供体通过抑制线粒体氧化磷酸化、减少活性氧生成发挥调控作用[2]。此外Ammonium tetrathiomolybdatTTMAbMole, M54856e还被证实可激活NRF2通路抑制铜死亡相关效应分子、并调控Akt/glucose摄取与乳酸代谢通路[1, 3]。在细胞模型研究中Ammonium tetrathiomolybdate四硫代钼酸盐在1.5 μM浓度下处理犬血管肉瘤细胞系DEN-HSA表现出显著的细胞毒性[4]。Ammonium tetrathiomolybdate在HepG2人肝癌细胞与HEK293人胚肾细胞中以1 μM–10 mM的浓度梯度处理24小时可观察到细胞特异性铜保留差异及氧化应激反应[5]。动物实验方面Ammonium tetrathiomolybdateTTM在C57BL/6小鼠胆管结扎纤维化模型中每日0.9 mg/kg剂量干预可缓解纤维化进程[6]此外在野百合碱Monocrotaline诱导的肺纤维化绵羊模型中Ammonium tetrathiomolybdateTTM干预可抑制血管生成与纤维化[7]。在TNBC三阴性乳腺癌小鼠模型中口服Ammonium tetrathiomolybdateTTM能维持血清铜蓝蛋白于8–17 mg/dL的水平显著抑制肺转移、降低LOX活性及胶原交联[8]。范例详解Front Oncol. 2025 Oct 10;15:1532772.AbMoel的Ammonium tetrathiomolybdateTTMAbMole, M54856在本研究中作为铜死亡的抑制剂通过对照实验以验证 FOXJ1 基因对宫颈癌细胞铜死亡的调控作用。研究结果表明FOXJ1基因过表达显著抑制宫颈癌细胞增殖、侵袭和迁移并促进铜死亡而TTM通过螯合铜离子抑制了铜死亡过程从而逆转了FOXJ1过表达的肿瘤抑制作用。图1. Overexpression of FOXJ1 decreased the proliferation, invasion, migration and the level of EMT process through the regulation of cuproptosis[9]参考文献及鸣谢[1] Ryumon, S.; Okui, T.; Kunisada, Y.; et al. Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma.Oncology reports2019,42(6), 2611-2621.[2] Durham, T.; Zander, D.; Stomeo, N.; et al. Chemistry, pharmacology, and cellular uptake mechanisms of thiometallate sulfide donors.British journal of pharmacology2020,177(4), 745-756.[3] Navratilova, J.; Karasova, M.; Kohutkova Lanova, M.; et al. Selective elimination of neuroblastoma cells by synergistic effect of Akt kinase inhibitor and tetrathiomolybdate.Journal of cellular and molecular medicine2017,21(9), 1859-1869.[4] Sloan, C. Q.; Rodriguez, C. O., Jr. In vitro effects of doxorubicin and tetrathiomolybdate on canine hemangiosarcoma cells.American journal of veterinary research2018,79(2), 219-225.[5] Sachdeva, S.; Maret, W. Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate.Toxicology mechanisms and methods2021,31(9), 690-698.[6] Song, M.; Song, Z.; Barve, S.; et al. Tetrathiomolybdate protects against bile duct ligation-induced cholestatic liver injury and fibrosis.The Journal of pharmacology and experimental therapeutics2008,325(2), 409-416.[7] Derseh, H. B.; Perera, K. U. E.; Dewage, S. N. V.; et al. Tetrathiomolybdate Treatment Attenuates Bleomycin-Induced Angiogenesis and Lung Pathology in a Sheep Model of Pulmonary Fibrosis.Frontiers in pharmacology2021,12, 700902.[8] Chan, N.; Willis, A.; Kornhauser, N.; et al. Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases.Clinical cancer research : an official journal of the American Association for Cancer Research2017,23(3), 666-676.[9] Cui, Y.; Liu, Z.; Zhang, L.; et al. Construction of a novel cuproptosis-related gene signature for predicting microenvironment, prognosis and therapeutic response in cervical cancer.Frontiers in oncology2025,15, 1532772.细胞实验参考细胞系AML cell cervical cancer cells方法The pENTER vector was used as a negative control. Ammonium tetrathiomolybdate (TTM) was purchased from AbMole (CAS No.:15060-55-6). Cells were treated with TTM at a final concentration of 40μM for 2 hours.浓度40μM处理时间2h.参考文献Front Oncol. 2025 Oct 10;15:1532772.*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C57BL/6N mice配制Distilled water剂量30 mg/kg给药处理Oral gavage参考文献Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H712-20.*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。