| CAS |
No.65271-80-9 |
| 中文名称 |
米托蒽醌 |
| 英文名称 |
Mitoxantrone |
| 分子式 |
C22H28N4O6 |
| 分子量 |
444.48 |
| 溶解性 |
Soluble in DMSO ≥5mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| EC |
EINECS 833-758-3 |
| MDL |
MFCD00242942 |
| SMILES |
C1=CC(=C2C(=C1NCCNCCO)C(=O)C3=C(C=CC(=C3C2=O)O)O)NCCNCCO |
| InChIKey |
KKZJGLLVHKMTCM-UHFFFAOYSA-N |
| InChI |
InChI=1S/C22H28N4O6/c27-11-9-23-5-7-25-13-1-2-14(26-8-6-24-10-12-28)18-17(13)21(31)19-15(29)3-4-16(30)20(19)22(18)32/h1-4，23-30H，5-12H2 |
| PubChem CID |
4212 |
| 靶点 |
Topoisomerase;PKC |
| 通路 |
DNA Damage/DNA Repair;TGF-beta/Smad;Epigenetics |
| 背景说明 |
是一种有效的拓扑异构酶II (topoisomerase II) 抑制剂，也可抑制蛋白激酶 C (PKC)，具有抗肿瘤活性。 |
| 生物活性 |
Mitoxantrone is a potent topoisomerase II inhibitor. Mitoxantrone also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM. Mitoxantrone induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone shows antitumor activity. Mitoxantrone also has anti-orthopoxvirus activity with EC50s of 0.25 μM and and 0.8 μM for cowpox and monkeypox， respectively.[1-5] |
| In Vitro |
Mitoxantrone 对组蛋白 H1 竞争性抑制 PKC，其 Ki 值为 6.3 μM，对磷脂酰丝氨酸和 ATP 非竞争性抑制[1]。 Mitoxantrone (0.5 μg/mL，48 h) 诱导 B-CLL 细胞减少。Mitoxantrone 诱导 DNA 片段化和聚 (ADP-核糖) 聚合酶 (PARP) 的蛋白水解切割，证明 Mitoxantrone 的细胞毒性作用是由于诱导细胞凋亡[2]。 Mitoxantrone 表明对人乳腺癌细胞系 MDA-MB-231 和 MCF-7 的细胞毒性，IC50 值分别为 18 和 196 nM[3]。 |
| In Vivo |
Mitoxantrone (IP，0-3.2 mg/kg/天) 在腹腔注射；植入 L1210 白血病的小鼠中以 1.6 mg/kg 产生显著数量的 60 天存活率[4]。 Mitoxantrone (IV，0-3.2 mg/kg/天) 显示出有效的抗肿瘤活性，并在皮下注射；植入的 Lewis 肺癌中以 3.2 mg/kg 产生 60% 的 ILS (寿命延长)[4]。 |
| 细胞实验 |
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]. |
| 动物实验 |
Mice: Mitoxantrone is tested for antitumor activity against experimental tumors in mice and the results are compared with those of seven antitumor antibiotics. The drugs are given IP or IV， in general on days 1， 5， and 9 following tumor inoculation. Mitoxantrone is given IP at the optimal dose (1.6 mg/kg/day; as a free base)[4]. |
| 数据来源文献 |
[1]. Takeuchi N， et al. Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. J Biochem. 1992 Dec;112(6):762-7.
[2]. Bellosillo B， et al. Mitoxantrone， a topoisomerase II inhibitor， induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.
[3]. Vibet S， et al. Differential subcellular distribution of mitoxantrone in relation to chemosensitization in two human breast cancer cell lines. Drug Metab Dispos. 2007 May;35(5):822-8.
[4]. 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.
[5]. Sharon E Altmann， et al. Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone. Antiviral Res. 2012 Feb;93(2):305-308. |
| 规格 |
25mg 50mg 100mg |
| 单位 |
瓶 |
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