Doxorubicin (Adriamycin) Licensed by Pfizer

Catalog No.S1208

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
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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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 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02839707 Not yet recruiting Fallopian Tube Clear Cell Adenocarcinoma|Fallopian Tube Endometrioid Adenocarcinoma|High Grade Fallopian Tube Serous Adenocarcinoma|High Grade Ovar  ...more Fallopian Tube Clear Cell Adenocarcinoma|Fallopian Tube Endometrioid Adenocarcinoma|High Grade Fallopian Tube Serous Adenocarcinoma|High Grade Ovarian Serous Adenocarcinoma|Ovarian Clear Cell Adenocarcinoma|Ovarian Endometrioid Adenocarcinoma|Ovarian Seromucinous Carcinoma|Primary Peritoneal High Grade Serous Adenocarcinoma|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma|Undifferentiated Fallopian Tube Carcinoma|Undifferentiated Ovarian Carcinoma National Cancer Institute (NCI) May 2017 Phase 2|Phase 3
NCT02743065 Not yet recruiting Hepatocellular Carcinoma Fifth Affiliated Hospital, Sun Yat-Sen University|Third A  ...more Fifth Affiliated Hospital, Sun Yat-Sen University|Third Affiliated Hospital, Sun Yat-Sen University September 2016 --
NCT01775475 Not yet recruiting AIDS-related Diffuse Large Cell Lymphoma|AIDS-related Diffuse Mixed Cell Lymphoma|AIDS-related Diffuse Small Cleaved Cell Lymphoma|AIDS-related Imm  ...more AIDS-related Diffuse Large Cell Lymphoma|AIDS-related Diffuse Mixed Cell Lymphoma|AIDS-related Diffuse Small Cleaved Cell Lymphoma|AIDS-related Immunoblastic Large Cell Lymphoma|AIDS-related Lymphoblastic Lymphoma|AIDS-related Peripheral/Systemic Lymphoma|AIDS-related Small Noncleaved Cell Lymphoma|Stage III AIDS-related Lymphoma|Stage IV AIDS-related Lymphoma AIDS Malignancy Consortium|National Cancer Institute (NCI  ...more AIDS Malignancy Consortium|National Cancer Institute (NCI)|The EMMES Corporation September 2016 Phase 2
NCT02783599 Not yet recruiting Soft Tissue Sarcoma Eli Lilly and Company September 2016 Phase 1
NCT02685657 Not yet recruiting Triple Negative Breast Cancer Russian Academy of Medical Sciences|Russian Society of Cl  ...more Russian Academy of Medical Sciences|Russian Society of Clinical Oncology September 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
2 years -80℃in solvent
Synonyms NSC 123127
Solubility (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.
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

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.

Tech Support

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.

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