Doxorubicin (Adriamycin) 化学構造
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製品説明

  • Compare Topoisomerase Inhibitors
    Topoisomerase製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 Doxorubicin (Adriamycin)は一種の抗生物質試薬ですが、腫瘍細胞の中にDNA topoisomerase IIを抑制し、DNA損傷とアポトーシスを誘導します。
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In vitro試験 Doxorubicin, an antibiotic anthracycline, is commonly considered to exert its anti-tumor activity at two fundamental levels, altering DNA and producing free radicals to trigger apoptosis of cancer cells through DNA damage. Doxorubicin can block the synthesis of DNA by intercalating into the DNA strand, and inhibits DNA topoisomerase II (TOP2). Doxorubicin is most effective when cells are rapidly proliferating and expressing high levels of TOP2. Additionally, Doxorubicin can trigger apoptosis by producing ceramide (which prompts apoptosis by activating p53 or other downstream pathways such as JNK), the degradation of Akt by serine threonine proteases, the mitochondrial release of cytochrome c, increased FasL (death receptor Fas/CD95 ligand) mRNA production, and a greater production of free radicals. [2] Pre-treatment with GSNO (nitrosoglutathione) suppresses the resistance in the doxorubicin-resistant breast cancer cell line MCF7/Dx, accompanied by enhanced protein glutathionylation and accumulation of doxorubicin in the nucleus. [3] Doxorubicin induced G2/M checkpoint arrest are attributed to elevated cyclin G2 (CycG2) expression and phospho-modification of proteins in the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) signaling pathways. [5] Doxorubicin inhibits AMP-activated protein kinase (AMPK), resulting in SIRT1 dysfunction, p53 accumulation, and increased cell death in mouse embryonic fibroblasts (MEFs) and cardiomyocytes, which can be further sensitized by pre-inhibition of AMPK. [6] Doxorubicin elicits a marked heat shock response, and that either inhibition or silencing of heat shock proteins enhance the Doxorubicin apoptotic effect in neuroblastoma cells. Nanomolar Doxorubicin treatment of neuroblastoma cells causes dose-dependent over-ubiquitination of a specific set of proteins in the absence of measurable inhibition of proteasome, and loss of activity of ubiquitinated enzymes such as lactate dehydrogenase and α-enolase, the protein ubiquination patterns of which is similar to those with proteasome inhibitor Bortezomib, indicating that Doxorubicin may also exert its effect by damaging proteins. [8]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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LB2518-MEL MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoixTWM2OD12MUOuNUBvVQ>? MnTFV2FPT0WU
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EB-3 NIT2eoxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTd5MT6wNkBvVQ>? MWnTRW5ITVJ?
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NCI-H446 MlPwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1z1TWlEPTB;MT6zN|c4OSEQvF2= M1SxfnNCVkeHUh?=
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NCI-H889 M4Pa[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkjkTWM2OD1zLkmzPFg3KM7:TR?= NFzLOnBUSU6JRWK=
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NCI-H2227 NHrt[WVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIfhbJhKSzVyPUWuN|YzOzFizszN NELGNlJUSU6JRWK=
DMS-53 MkDMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3K1TGlEPTB;Nj6xO|ExPiEQvF2= NH72ZXZUSU6JRWK=
LB771-HNC NFeyZ4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWfJR|UxRTZwNE[4NFYh|ryP MX7TRW5ITVJ?
BB49-HNC NFTWO4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1zmSGlEPTB;Nz60NVc6OSEQvF2= M2\yU3NCVkeHUh?=
MDA-MB-415 M{fDbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH60TmNKSzVyPUeuOVc{ODNizszN NH7GdVhUSU6JRWK=
TALL-1 MlnGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zmVWlEPTB;Nz65Olg5KM7:TR?= MWHTRW5ITVJ?
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... Click to View More Cell Line Experimental Data

In vivo試験 In vivo, Doxorubicin in combination with adenoviral MnSOD (AdMnSOD) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has the greatest effect in decreasing the volumes of MB231 tumors and prolonging survival of mice. [1] Although its use is limited by the chronic and acute toxic side effects it produces, Doxorubicin is essential in treating breast and oesophageal carcinomas, solid tumours in childhood, osteosarcomas, Kaposi's sarcoma, soft tissue sarcomas, and Hodgkin and non-Hodgkin lymphomas. [2]
臨床試験 A Phase III study of Doxorubicin alone vs. Doxorubicin in combination with TH-302 in subjects with locally advanced unresectable or metastatic soft tissue sarcoma is currently ongoing.
特集

プロトコル (参考用のみ)

動物実験: [1]

動物モデル Female athymic nude mice injected s.c. with MB231 cells
製剤 Dissolved in DMSO, and diluted in saline
投薬量 3 mg/kg/day
投与方法 Delivered intratumorly

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Doxorubicin (Adriamycin) SDF
分子量 579.98
化学式

C27H29NO11.HCl

CAS No. 25316-40-9
保管 3年-20℃
2年-80℃in solvent
別名 NSC 123127
溶解度 (25°C) * In vitro DMSO 100 mg/mL warming (172.41 mM)
Water 20 mg/mL (34.48 mM)
Ethanol <1 mg/mL
In vivo
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 (8S,10S)-10-((2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl-tetrahydro-2H-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione hydrochloride

文献中の引用 (31)

Frequently Asked Questions

  • Question 1
    Why the IC50 of the compound varied over time in our measurement?

    Answer: Sometimes the IC50 value might vary between different batch of compounds due to the slight differences in purity. If different IC50 was seen in the same batch of compound, the problem may lies in the process of dissolvement. Make sure that you see no particles and the solution is clear with your stock solution.

技術サポート&よくある質問(FAQ)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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