| Description | Mitoxantrone (mitozantrone) is an inhibitor of topoisomerase II (Topo II), an inhibitor of protein kinase C (PKC) (IC50=8.5 μM). Mitoxantrone has antitumor activity for the treatment of acute myeloid leukemia, hepatocellular carcinoma, and breast cancer. |
| In vitro | 方法：人乳腺癌细胞 MCF7 用 Mitoxantrone (0.07-9.36 µM) 处理 48 h，使用 SRB assay 测定细胞活力。结果：MCF7 细胞在 Mitoxantrone 1.17 µM 剂量下达到对应于 IC50 的抑制作用。[1]方法：骨肉瘤细胞 U2OS 用 Mitoxantrone (0.2-1 µM) 处理 48 h，使用 Western Blot 检测靶点蛋白表达水平。结果：Mitoxantrone 处理增加了 Caspase-3 和 PARP1 的裂解。Mitoxantrone 处理还增加了骨肉瘤细胞中 Bax 和 Bim EL 的表达。然而，Mitoxantrone 处理降低了 Bcl-2 的表达。[2] |
| In vivo | 方法：为测试对，将 Mitoxantrone (0.4-3.2 mg/kg) 腹腔注射给注射白血病细胞 L1210 的 CDF1 小鼠，每天一次。结果：以最佳剂量 (1.6 mg/kg/天) 给予 Mitoxantrone 产生了具有统计学意义的 60 天存活率。[3] |
| Cell experiments | The human breast carcinoma cell lines MDA-MB-231 and MCF-7 are seeded in standard 96-well plates. One day after seeding, the culture medium is changed and replaced by medium containing different concentration of Mitoxantrone (10-5 to 5 μM) with or without DHA (30 μM) during 7 days. Viability of cells are measured as a whole by the tetrazolium salt assay[3]. |
| Target activity | PKC:8.5 μM. |
| Synonyms | 米托蒽醌, mitozantrone |
| molecular weight | 444.48 |
| Molecular formula | C22H28N4O6 |
| CAS | 65271-80-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: < 1 mg/mL (insoluble or slightly soluble) DMSO: 88 mg/mL (197.98 mM) H2O: < 1 mg/mL (insoluble or slightly soluble) |
| References | 1. Guerriero E, et al. Vitamin C effect on mitoxantrone-induced cytotoxicity in human breast cancer cell lines. PLoS One. 2014 Dec 22;9(12):e115287. 2. Park SH, et al. Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway. Oncol Lett. 2018 Jun;15(6):9687-9696. 3. Fujimoto S, et al. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol. 1982;8(2):157-62. 4. Oudard S, et al. J Urol, 2003, 169(5), 1729-1734. 5. Herman EH, et al. J Mol Cell Cardiol, 1997, 29(9), 2415-2430. 6. Dong L, Shen S, Chen W, et al. Discovery of Novel Inhibitors Targeting Human O-GlcNAcase: Docking-Based Virtual Screening, Biological Evaluation, Structural Modification, and Molecular Dynamics Simulation[J]. Journal of chemical information and modeling. 2019, 59(10): 4374-4382. 7. Zeng X, Zhu S, Lu W, et al. Target identification among known drugs by deep learning from heterogeneous networks[J]. Chemical Science. 2020, 11(7): 1775-1797. |
| Citations | 1. Zeng X, Zhu S, Lu W, et al. Target identification among known drugs by deep learning from heterogeneous networks. Chemical Science. 2020, 11(7): 1775-1797. 2. Dong L, Shen S, Chen W, et al. Discovery of Novel Inhibitors Targeting Human O-GlcNAcase: Docking-Based Virtual Screening, Biological Evaluation, Structural Modification, and Molecular Dynamics Simulation. Journal of chemical information and modeling. 2019, 59(10): 4374-4382. 3. Zeng R, Yang X M, Li H W, et al.Simplified Derivatives of Tetrandrine as Potent and Specific P-gp Inhibitors to Reverse Multidrug Resistance in Cancer Chemotherapy.Journal of Medicinal Chemistry.2023 4. Ba D, Li H, Liu R, et al.Exploratory study on the efficacy of bortezomib combining mitoxantrone or CD22-CAR T therapy targeting CD19-negative relapse after CD19-CAR T cell therapy with a simpler cell-line-based model.Apoptosis.2023: 1-12. 5. Yu T, Zeng R, Guan Y, et al.Discovery of new tricyclic spiroindole derivatives as potent P-glycoprotein inhibitors for reversing multidrug resistance enabled by synthetic methodology-based library.RSC Medicinal Chemistry.2024 |