Doxorubicin (Adriamycin) Licensed by Pfizer

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis in tumor cells.

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Doxorubicin (Adriamycin) Chemical Structure

Doxorubicin (Adriamycin) Chemical Structure
Molecular Weight: 579.98

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Product Information

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  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis in tumor cells.
Targets Topo II [1]
(Tumor cells)
In vitro 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
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... Click to View More Cell Line Experimental Data

In vivo 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]
Features

Protocol(Only for Reference)

Animal Study: [1]

Animal Models Female athymic nude mice injected s.c. with MB231 cells
Formulation Dissolved in DMSO, and diluted in saline
Dosages 3 mg/kg/day
Administration Delivered intratumorly

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

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
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

References

[1] Sun W, et al. Cancer Res, 2009, 69(10), 4294-4300.

[2] Granados-Principal S, et al. Food Chem Toxicol, 2010, 48(6), 1425-1438.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-01-10)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02648477 Not yet recruiting Estrogen Receptor Negative|Estrogen Receptor Positive|HER2/Neu Negative|Progesterone Receptor Negative|Progesterone Receptor Positive|Stage IV Brea  ...more Estrogen Receptor Negative|Estrogen Receptor Positive|HER2/Neu Negative|Progesterone Receptor Negative|Progesterone Receptor Positive|Stage IV Breast Cancer|Triple-Negative Breast Carcinoma City of Hope Medical Center|National Cancer Institute (NCI) June 2016 Phase 2
NCT02456857 Not yet recruiting Breast Cancer M.D. Anderson Cancer Center March 2016 Phase 2
NCT02446600 Not yet recruiting Fallopian Tube Clear Cell Adenocarcinoma|Fallopian Tube Transitional Cell Carcinoma|Malignant Ovarian Mixed Epithelial Tumor|Ovarian Clear Cell Ade  ...more Fallopian Tube Clear Cell Adenocarcinoma|Fallopian Tube Transitional Cell Carcinoma|Malignant Ovarian Mixed Epithelial Tumor|Ovarian Clear Cell Adenocarcinoma|Ovarian Endometrioid Tumor|Ovarian Serous Tumor|Ovarian Transitional Cell Carcinoma|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma|Undifferentiated Fallopian Tube Carcinoma|Undifferentiated Ovarian Carcinoma National Cancer Institute (NCI) February 2016 Phase 3
NCT02637375 Not yet recruiting Breast Cancer University of Chicago February 2016 --
NCT02623972 Not yet recruiting Inflammatory Breast Cancer|Human Epidermal Growth Factor 2 Negative Carcinoma of Breast Dana-Farber Cancer Institute|Eisai Inc. January 2016 Phase 2

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Chemical Information

Download Doxorubicin (Adriamycin) SDF
Molecular Weight (MW) 579.98
Formula

C27H29NO11.HCl

CAS No. 25316-40-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms NSC 123127
Solubility (25°C) * In vitro DMSO 100 mg/mL warmed (172.41 mM)
Water 20 mg/mL (34.48 mM)
Ethanol <1 mg/mL (<1 mM)
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.
Chemical Name (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

Customer Product Validation (6)


Click to enlarge
Rating
Source Sci Transl Med, 2015, 7(284): 284ra57 . Doxorubicin (Adriamycin) purchased from Selleck
Method Apoptotic Response Assay
Cell Lines MDA-MB-231 cells
Concentrations 10 mg/kg
Incubation Time 24 h
Results The apoptotic response inMDA-MB-231 (human triple-negative breast) tumors, as tested by the device, was significantly elevated to 17.5% from 7.4%by the addition of lapatinib to doxorubicin in reservoirs.

Click to enlarge
Rating
Source Cancer Res 2014 74, 298-308. Doxorubicin (Adriamycin) purchased from Selleck
Method MTT assay
Cell Lines H1299, A549, Hep3B, HT1080, HCT116, MCF7
Concentrations
Incubation Time 48 h
Results Hypoxic (1% O2 ) conditions for 48 hours. The IC50 value for cisplatin or doxorubicin significantly increased under hypoxia in H1299, A549, Hep3B, and HT1080, but did not in HCT116 and MCF7

Click to enlarge
Rating
Source J Biomed Mater Res Part A 2012 10.1002/jbm.a.34064. Doxorubicin (Adriamycin) purchased from Selleck
Method Release experiment
Cell Lines N.A.
Concentrations 0.25mg/mL
Incubation Time 2-10 h
Results Doxorubicin was loaded by equilibrium partitioning in the following manner: a stock solution of doxorubicin was prepared in 2 wt % DMSO in 1 PBS (pH 7.4) at a concentration of 0.25 mg/mL. A 5 mg/mL concentration of crushed particles (75–150 um) of P(MAA-g-EG) or P(MAA-g-EG) containing PMMA nanoparticles to doxorubicin stock solution was allowed to stir slowly for 2 h.

Click to enlarge
Rating
Source PLoS One 2014 9, e94309. Doxorubicin (Adriamycin) purchased from Selleck
Method Flow Cytometry Analysis
Cell Lines K-562, DL cells
Concentrations 5.85 uM
Incubation Time 24 h
Results It was extended our observation of DOX-uptake at microscopic level for visualizing the presence of significantly higher DOX concentration intracellularly in K-562 and DL. As observed in I and J, the intracellular level of DOX is significantly higher in cells treated with DOX-PCL63-b-PNVP90 compared to free DOX suggesting high drug delivery efficiency of the compound.

Click to enlarge
Rating
Source PLoS One 2013 8(1), e54595. Doxorubicin (Adriamycin) purchased from Selleck
Method MTT assay
Cell Lines Huh7, THLE2, Hep5B cells
Concentrations 0.016-52 uM
Incubation Time 74 h
Results Cytotoxicity by doxorubicin was measured by MTT assay atvarying concentrations on the HCC lines Huh7, THLE2, Hep3B.

Click to enlarge
Rating
Source 2014 Dr Milica Pesic from Institute for Biological Research. Doxorubicin (Adriamycin) purchased from Selleck
Method Transwell membranes assembled
Cell Lines COR-L23, RH460 cells
Concentrations 50 nM, 1 uM
Incubation Time 24 h
Results Evaluation of DOX effect on cancer cell invasion in combination with inhibitors of CXCR4 receptor (WZ811) and focal adhesion kinase (FAK; PF-573228). Two DOX resistant non-small cell lung carcinoma (NSCLC) cell lines were employed: COR-L23 that shows intrinsic resistance to DOX and RH460 with classical acquired multidrug resistant phenotype. The results show that DOX, classical cytotoxic drug, potentates known anti-migratory effects of CXCR4 receptor inhibitor (WZ811) and FAK inhibitor (PF-573228) in both types of resistant NSCLC cell lines. WZ811 had more pronounced and significant effect with DOX in RH460 cells while PF-573228 was more effective with DOX oin COR-L23 cell line.

Product Use Citation (28)

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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