65271-80-9

• 常用中文名：米托蒽醌
• 常用英文名：Mitoxantrone
• CAS号：65271-80-9
• 分子式：C₂₂H₂₈N₄O₆
• 分子量：444.481
• 相关类别： 原料药 抗肿瘤药 抗肿瘤辅助用药
• 发布时间：2018-06-23 20:03:41
• 更新时间：2024-01-02 21:17:23
• Mitoxantrone是拓扑异构酶II (topoisomerase II)的抑制剂；也可抑制蛋白激酶C (PKC), IC50值为8.5 μM。

名称

• 中文名: 米托蒽醌
• 英文名: mitoxantrone
• 中文别名: 1,4-二羟基-5,8-双[[2-[(2-羟乙基)氨基]乙基]氨基]-9,10-蒽醌; 米拖蒽醌
• 英文别名: 1,4-Dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)-9,10-anthraquinone; mitoxanthrone; 1,4-Dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracen-9,10-dion; UNII-BZ114NVM5P; MFCD00242942; PharmasubstanceEP4; 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyéthyl)amino]éthyl}amino)anthracène-9,10-dione; DHAQ; 1,4-dihydroxy-5,8-bis[[2-(2-hydroxy-ethylamino)ethyl]amino]anthraquinone; 9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis((2-((2-hydroxyethyl)amino)ethyl)amino)-; dihydroxyanthraquinone; 1,4-dehydroxy-5,8-bis[[[2-(2-hydroxyethyl)amino]ethyl]amino]-9,19-antracenedion; 9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-; MITOXANTRONUM AND THE INTERMEDIATES; 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione; 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthraquinone; 1,4-bis-[2-(2-hydroxyethylamino)ethylamino]-5,8-dihydroxy-9,10-anthracenedione; 1,4-bis[2-(2-hydroxyethylamino)ethylamino]-5,8-dihydroxyanthraquinone; Mitoxantrone; [3H]-Mitoxantrone; MITOXANTRONUM

物化性质

• 密度: 1.5±0.1 g/cm3
• 沸点: 805.7±65.0 °C at 760 mmHg
• 熔点: 170-174ºC
• 分子式: C₂₂H₂₈N₄O₆
• 分子量: 444.481
• 闪点: 441.1±34.3 °C
• 精确质量: 444.200897
• PSA: 163.18000
• LogP: 0.45
• 外观性状: 蓝色粉末
• 蒸汽压: 0.0±3.0 mmHg at 25°C
• 折射率: 1.709
• 储存条件: -20°C Freezer
• 水溶解性: 水溶性：实际上不溶；微溶：甲醇；不溶：丙酮,氯仿

生物活性

• 描述: Mitoxantrone是拓扑异构酶II (topoisomerase II)的抑制剂；也可抑制蛋白激酶C (PKC), IC50值为8.5 μM。
• 相关类别:
  信号通路 >> 表观遗传学 >> PKC
  信号通路 >> TGF-beta/Smad 信号通路 >> PKC
  信号通路 >> 细胞周期/DNA损伤 >> 拓扑异构酶
  研究领域 >> 癌症
• 靶点:

  PKC:8.5 μM (IC50)

  Topoisomerase II

• 体外研究: 米托蒽醌以相对于组蛋白H1的竞争性方式抑制PKC,并且其Ki值为6.3μM并且以非竞争性方式相对于磷脂酰丝氨酸和ATP [1]。用米托蒽醌(0.5μg/ mL)处理B-CLL细胞48小时诱导细胞活力降低。米托蒽醌诱导DNA片段化和聚(ADP-核糖)聚合酶(PARP)的蛋白水解切割,证明米托蒽醌的细胞毒性作用是由于诱导细胞凋亡[2]。米托蒽醌显示对人乳腺癌细胞系MDA-MB-231和MCF-7的细胞毒性,IC50值分别为18和196 nM [3]。
• 体内研究: 米托蒽醌以最佳剂量(1.6mg/kg /天;作为游离碱)给予IP,在IP植入L1210白血病的小鼠中产生统计学上显着数量的60天存活者(疗效)。在SC植入Lewis肺癌中,米托蒽醌和静脉注射ADM也显示出有效的抗肿瘤活性,分别产生60％和45％的ILS [4]。
• 细胞实验: 将人乳腺癌细胞系MDA-MB-231和MCF-7接种在标准96孔板中。接种后一天，更换培养基，并在7天内用含有或不含DHA（30μM）的不同浓度的米托蒽醌（10-5至5μM）的培养基替换。通过四唑盐测定[3]整体测量细胞活力。
• 动物实验: 小鼠：测试米托蒽醌对小鼠中实验性肿瘤的抗肿瘤活性，并将结果与七种抗肿瘤抗生素的结果进行比较。通常在肿瘤接种后第1,5和9天给予IP或IV的药物。米托蒽醌以最佳剂量（1.6mg / kg /天;作为游离碱）给予IP [4]。
• 参考文献:

  [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.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : CB5748500 CHEMICAL NAME : Anthraquinone, 5,8-bis((2-((2-hydroxyethyl)amino)ethyl)amino)-1,4-di hydroxy- CAS REGISTRY NUMBER : 65271-80-9 LAST UPDATED : 199612 DATA ITEMS CITED : 22 MOLECULAR FORMULA : C22-H28-N4-O6 MOLECULAR WEIGHT : 444.54 WISWESSER LINE NOTATION : L C666 BV IVJ DQ GQ KM2M2Q NM2M2Q HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 7100 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 20910 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 6600 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 86500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 16 mg/kg/6W-I TOXIC EFFECTS : Cardiac - EKG changes not diagnostic of specified effects Liver - other changes Blood - changes in leukocyte (WBC) count TYPE OF TEST : Specific locus test TYPE OF TEST : Sex chromosome loss and nondisjunction TYPE OF TEST : DNA damage MUTATION DATA TYPE OF TEST : Mutation in mammalian somatic cells TEST SYSTEM : Rodent - hamster Lung DOSE/DURATION : 100 ng/L REFERENCE : PAACA3 Proceedings of the American Association for Cancer Research. (Waverly Press, 428 E. Preston St., Baltimore, MD 21202) V.1- 1954- Volume(issue)/page/year: 26,217,1985

安全

• 危害码 (欧洲): T,T+
• 风险声明 (欧洲): R46
• 安全声明 (欧洲): 53-36/37/39-45-22
• 危险品运输编码: 3077.0
• WGK德国: 3
• RTECS号: CB5748500
• 危险类别: 9.0

上下游产品

上游产品  3
81-59-4 131401-54-2 111-41-1
下游产品  0