Mitoxantrone (mitozantrone)
(Synonyms: 米托蒽醌; Mitozantrone; NSC 301739) 目录号 : GC32714
Mitoxantrone作为一种有效的拓扑异构酶II抑制剂,它可以抑制DNA复制,同时它是一种线粒体钙单转运蛋白(MCU)抑制剂,它还能抑制蛋白激酶C (PKC)活性,IC50为8.5 µM。.
Cas No.:65271-80-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
B-chronic lymphocytic leukaemia (B-CLL) cells |
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Preparation Method |
Cells were incubated for 48 h with 0.5 µg/ml mitoxantrone. |
|
Reaction Conditions |
0.5µg/ml; 48h |
|
Applications |
Mitoxantrone induces apoptosis in B-CLL lymphocytes. |
| Animal experiment [2]: | |
|
Animal models |
BDF female mice (L1210 cell tumor model) |
|
Preparation Method |
The drugs were given IP or IV, in general on days 1, 5, and 9 following tumor inoculation. |
|
Dosage form |
0-3.2 mg/kg/day; i.p; on days 1, 5, and 9 following tumor inoculation |
|
Applications |
The increase life span (ILS) of tumor-bearing mice increased by more than 100% after intravenous administration of mitoxantrone. |
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References: [1]. Bellosillo B, Colomer D, et,al. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6. doi: 10.1046/j.1365-2141.1998.00520.x. PMID: 9450803. | |
Mitoxantrone is an antitumor anthrandione derivative. As a potent inhibitor of topoisomerase II, Mitoxantrone can inhibit DNA replication and induce single and double strand breaks through hydrogen bond insertion into DNA. Mitoxantrone is an inhibitor of mitochondrial calcium monotransporter (MCU), which can inhibit calcium entering into mitochondria and prevent mitochondrial calcium overload [1-3]. Mitoxantrone also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 µM.
Mitoxantrone(0.5µg/ml; 48h) induced DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), the cytotoxic effect of mitoxantrone was due to induction of apoptosis[4]. Mitoxantrone (50 nM; 24 h) reduced the triglyceride (TG) levels and total cholesterol levels in LMH cells(a steatosis cell model). Mitoxantrone improves hepatic steatosis in broilers as well as reduces circulating lipid levels and fat accumulation in broilers[5].
After mitoxantrone treatment(0-3.2 mg/kg/day; i.p; on days 1, 5, and 9 following tumor inoculation), the increase life span (ILS) of tumor-bearing mice increased by more than 100%[6]. Mitoxantrone persistently suppresses B cells in vivo and led to an enrichment of neutrophils and immunomodulatory CD8(low) T cells[7].
References:
[1]. Nathanson L. Mitoxantrone. Cancer Treat Rev. 1984 Dec;11(4):289-93. doi: 10.1016/0305-7372(84)90025-2. PMID: 6534511.
[2]. Durr FE, Wallace RE, et,al. Molecular and biochemical pharmacology of mitoxantrone. Cancer Treat Rev. 1983 Dec;10 Suppl B:3-11. doi: 10.1016/0305-7372(83)90016-6. PMID: 6362876.
[3]. Arduino DM, Wettmarshausen J, et,al. Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening. Mol Cell. 2017 Aug 17;67(4):711-723.e7. doi: 10.1016/j.molcel.2017.07.019. PMID: 28820965; PMCID: PMC5825229.
[4]. Bellosillo B, Colomer D, et,al. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6. doi: 10.1046/j.1365-2141.1998.00520.x. PMID: 9450803.
[5]. Vibet S, MahÉo K, 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. doi: 10.1124/dmd.106.013474. Epub 2007 Feb 12. PMID: 17296624.
[6]. Fujimoto S, Ogawa M. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol. 1982;8(2):157-62. doi: 10.1007/BF00255476. PMID: 7105379.
[7]. Chanvillard C, Millward JM, et,al. Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis. PLoS One. 2012;7(6):e39625. doi: 10.1371/journal.pone.0039625. Epub 2012 Jun 29. PMID: 22768101; PMCID: PMC3387260.
米托蒽醌Mitoxantrone是一种抗肿瘤的蒽醌衍生物。作为一种有效的拓扑异构酶II抑制剂,Mitoxantrone可以抑制DNA复制,通过氢键插入DNA诱导单链和双链断裂。Mitoxantrone也是一种线粒体钙单转运体(MCU)抑制剂,可以抑制钙进入线粒体,防止线粒体钙超载[1-3]。
Mitoxantrone (0.5µg/ml; 48h)诱导DNA断裂和聚腺苷核糖聚合酶(PARP)的蛋白水解裂解,其细胞毒作用是由于诱导细胞凋亡所致[4]。Mitoxantrone (50 nM; 24 h)降低了LMH细胞(脂肪变性细胞模型)中的甘油三酯(TG)水平和总胆固醇水平。Mitoxantrone改善肉仔鸡肝脏脂肪变性,降低肉仔鸡循环脂质水平和脂肪积累[5]。
经Mitoxantrone治疗(0-3.2 mg/kg/day; i.p; on days 1, 5, and 9 following tumor inoculation)后,荷瘤小鼠的延长寿命(ILS)提高100%以上[6]。Mitoxantrone在体内持续抑制B细胞,导致中性粒细胞和免疫调节性CD8(低)T细胞的富集[7]。
| Cas No. | 65271-80-9 | SDF | |
| 别名 | 米托蒽醌; Mitozantrone; NSC 301739 | ||
| Canonical SMILES | O=C1C2=C(C(NCCNCCO)=CC=C2NCCNCCO)C(C3=C(O)C=CC(O)=C13)=O | ||
| 分子式 | C22H28N4O6 | 分子量 | 444.48 |
| 溶解度 | DMSO : ≥ 150 mg/mL (337.47 mM) | 储存条件 | -20°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2498 mL | 11.2491 mL | 22.4982 mL |
| 5 mM | 0.45 mL | 2.2498 mL | 4.4996 mL |
| 10 mM | 0.225 mL | 1.1249 mL | 2.2498 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Mitoxantrone, More than Just Another Topoisomerase II Poison
Med Res Rev 2016 Mar;36(2):248-99.PMID:26286294DOI:10.1002/med.21364.
Mitoxantrone is a synthetic anthracenedione originally developed to improve the therapeutic profile of the anthracyclines and is commonly applied in the treatment of breast and prostate cancers, lymphomas, and leukemias. A comprehensive overview of the drug's molecular, biochemical, and cellular pharmacology is presented here, beginning with the cardiotoxic nature of its predecessor doxorubicin and how these properties shaped the pharmacology of Mitoxantrone itself. Although Mitoxantrone is firmly established as a DNA topoisomerase II poison within mammalian cells, it is now clear that the drug interacts with a much broader range of biological macromolecules both covalently and noncovalently. Here, we consider each of these interactions in the context of their wider biological relevance to cancer therapy and highlight how they may be exploited to further enhance the therapeutic value of Mitoxantrone. In doing so, it is now clear that Mitoxantrone is more than just another topoisomerase II poison.
[Mitoxantrone]
Neurologia 2003 Jul-Aug;18(6):318-23.PMID:12838451doi
Mitoxantrone is an antineoplastic agent that exerts a potent immunosuppresive effect, including suppression of B cell immunity and reduction of T cell numbers. Clinical trials have shown that Mitoxantrone has a statistically significant impact on reduction of relapse rate and delays disability progression in patients with relapsing remitting (RR) multiple sclerosis (MS) or secondary progressive (SP) MS. Treatment is well tolerated, but the risk of cardiotoxicity at higher cumulative doses is likely to limit the duration of treatment. The maximum cumulative dose recommended is 140 mg/m2. In 2000, the FDA (Food and Drug Administration) approved the use of Mitoxantrone for the treatment of active RRMS, SPMS and progressing relapsing (PR) MS.
Mitoxantrone-Surfactant Interactions: A Physicochemical Overview
Molecules 2016 Oct 13;21(10):1356.PMID:27754390DOI:10.3390/molecules21101356.
Mitoxantrone is a synthetic anticancer drug used clinically in the treatment of different types of cancer. It was developed as a doxorubicin analogue in a program to find drugs with improved antitumor activity and decreased cardiotoxicity compared with the anthracyclines. As the cell membrane is the first barrier encountered by anticancer drugs before reaching the DNA sites inside the cells and as surfactant micelles are known as simple model systems for biological membranes, the drugs-surfactant interaction has been the subject of great research interest. Further, quantitative understanding of the interactions of drugs with biomimicking structures like surfactant micelles may provide helpful information for the control of physicochemical properties and bioactivities of encapsulated drugs in order to design better delivery systems with possible biomedical applications. The present review describes the physicochemical aspects of the interactions between the anticancer drug Mitoxantrone and different surfactants. Mitoxantrone-micelle binding constants, partitions coefficient of the drug between aqueous and micellar phases and the corresponding Gibbs free energy for the above processes, and the probable location of drug molecules in the micelles are discussed.
A case of Mitoxantrone extravasation
J Oncol Pharm Pract 2020 Jul;26(5):1270-1273.PMID:31902285DOI:10.1177/1078155219893736.
Introduction: Mitoxantrone is a chemotherapeutic agent approved for various diseases. The literature has been conflicting in classifying Mitoxantrone as a vesicant or irritant. Case report: We report a patient who had an extravasation of Mitoxantrone. Mitoxantrone was administered in 50 ml normal saline. After Mitoxantrone was completely infused, the site appeared edematous and the blue color of Mitoxantrone developed beneath the skin. The patient reported pain. Management and outcome: The extravasation was treated with dexrazoxane and cold compresses. The pain improved each day. However, blistering developed five weeks later and the patient ultimately required surgical intervention for debridement and grafting. Discussion: Extravasation events are rare and there are few controlled studies. Because of the similarities in chemical structures and mechanism of actions between Mitoxantrone and anthracyclines, Mitoxantrone extravasation is often treated similar to anthracyclines. Mitoxantrone's classification is unclear, as some literature classifies it as a vesicant and others as an irritant. Our case supports the categorization of Mitoxantrone as a vesicant.
The current role of Mitoxantrone in the treatment of multiple sclerosis
Expert Rev Neurother 2014 Jun;14(6):607-16.PMID:24834466DOI:10.1586/14737175.2014.915742.
Mitoxantrone is an immunosuppressive drug approved for aggressive relapsing and progressive multiple sclerosis. In recent years, its use has decreased due to the risk of severe adverse events and the introduction of novel therapies, such as natalizumab or fingolimod. Mitoxantrone is effective in reducing inflammatory activity by decreasing the number of relapses and MRI lesions and simultaneously decreasing the worsening of disability. Apart from its role as a second/third-line therapy, some studies suggest its use as an induction therapy. However, Mitoxantrone use is limited because of its potential risk of severe adverse events, such as cardiotoxicity and the induction of therapy-related acute leukemia. Genetic markers are on evaluation to predict side effects and therapeutic efficacy, which is consistent with the direction of personalized treatment. Considering its efficacy and the potential risks, Mitoxantrone use is limited to active patients after a careful, individualized evaluation of the risk/benefit balance.