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Doxorubicin (Adriamycin) HCl

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Catalog No.
A1832
抗肿瘤抗生素,抑制TOPO II。
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
10mg
¥ 600.00
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25mg
¥ 840.00
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100mg
¥ 1,920.00
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Background

Doxorubicin is a semi-synthesized anticancer agent derived from bacterial culture. [1] It is an anthracycline antibiotic. It is been widely used in blood cancers, solid tumors and sarcomas.

Doxorubicin intercalates into DNA double strand and inhibits the progression of DNA topoisomerase II, stopping replication process. [2] Doxorubicin also induces histone eviction from open chromatin, causing DNA damage and epigenetic deregulation. [3]

Doxorubicin is administrated intravenously. Approximately 75% of doxorubicin and its metabolites bind to plasma protein. Doxorubicin does not cross blood brain barrier. 50% of the drug is eliminated unchanged from the body mainly though bile excretion. The remaining undergoes one-electron reduction, two-electron reduction, and deglycosidation. The major metabolite is a potent membrane ion pump inhibitor, which is associated with cardiomyopathy. [4]

References:
[1]Brayfield, A, ed. (2013). Doxorubicin. Martindale: The Complete Drug Reference. Pharmaceutical Press. Retrieved 15 April 2014.
[2]Pommier Y., et al. (2010). DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chemistry & Biology 17 (5): 421–433.
[3]Pang, B., et al. (2013). Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nature Communications 4 (5): 1908
[4]Boucek RJ., et al. (1987). The major metabolite of doxorubicin is a potent inhibitor of membrane-associated ion pumps. A correlative study of cardiac muscle with isolated membrane fractions. J of Biol Chem 262: 15851-15856.

文献引用

1. Lin KH, Xie A, et al. "Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity." Cell Metab. 2019 Feb 5. pii: S1550-4131(19)30011-7. PMID:30773463
2. Andrew Goodspeed, Annie Jean, et al. "Low MSH2 protein levels identify muscle-invasive bladder cancer resistant to cisplatin." bioRxiv. 2018 June 29.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt579.98
Cas No.25316-40-9
FormulaC27H29NO11.HCl
Solubility≥29mg/mL in DMSO
Chemical Name(7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride
SDFDownload SDF
Canonical SMILESCC1C(C(CC(O1)OC2CC(CC3=C(C4=C(C(=C23)O)C(=O)C5=C(C4=O)C=CC=C5OC)O)(C(=O)CO)O)N)O.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

H9c2 细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

1 μg/ml, 2小时

实验结果

使用逐渐增加浓度的doxorubicin处理H9c2细胞2小时,浓度为0.1、0.3、0.5和1.0 μg/ml,分别相当于0.17、0.52、0.85和1.71 μM,或使用0.3 μg/ml(相当于0.52μM)的doxorubicin处理不同时间。Doxorubicin以时间和剂量依赖性的方式诱导AMPKα(Thr 172)及其下游乙酰辅酶A羧化酶(ACC,Ser 79)的磷酸化。Doxorubicin处理1小时后,AMPKα的磷酸化较为显著,药物效果维持至少6小时。LKB1可能是AMPK的上游激酶,在H9c2细胞中,Doxorubicin也激活LKB1。

动物实验 [2]:

动物模型

C57BL/10 小鼠

剂量

腹膜内注射,20 mg/kg

实验结果

与对照组相比,doxorubicin注射后5天,小鼠的收缩期(LVP, -29%; dP/dtmax, -45%)、舒张期(dP/dtmin, -44%; stiffness, +275%)以及全局左心室(LV)功能(SV, -61%; HR, -18%; CO,-68%)显著受损。与安慰剂小鼠相比,心脏脂质过氧化活性(+37%)和心脏硝基酪氨酸蛋白表达(+204%)均有所增加。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Chen M B, Wu X Y, Gu J H, et al. Activation of AMP-activated protein kinase contributes to doxorubicin-induced cell death and apoptosis in cultured myocardial H9c2 cells. Cell biochemistry and biophysics, 2011, 60(3): 311-322.

[2] Riad A, Bien S, Westermann D, et al. Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice. Cancer research, 2009, 69(2): 695-699.

生物活性

描述 Doxorubicin是一种抗肿瘤抗生素,对DNA拓扑异构酶Ⅱ具有抑制作用。
靶点 MCF-7          
IC50 100 nM          

质量控制

化学结构

Doxorubicin (Adriamycin)

相关生物数据

Doxorubicin (Adriamycin)