Doxorubicin (Adriamycin) HCl

Licensed by Pfizer Catalog No.S1208 Synonyms: NSC 123127, DOX, Doxorubicin hydrochloride, Hydroxydaunorubicin HCl

For research use only.

Doxorubicin (Adriamycin, NSC 123127, DOX, Hydroxydaunorubicin) HCl is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage, mitophagy and apoptosis in tumor cells. Doxorubicin reduces basal phosphorylation of AMPK. Doxorubicin is used in the concomitant treatment of HIV-infected patients but is found to be at high risk of HBV reactivation.

Doxorubicin (Adriamycin) HCl Chemical Structure

CAS No. 25316-40-9

Selleck's Doxorubicin (Adriamycin) HCl has been cited by 799 publications

Purity & Quality Control

Choose Selective Antineoplastic and Immunosuppressive Antibiotics Inhibitors

Biological Activity

Description Doxorubicin (Adriamycin, NSC 123127, DOX, Hydroxydaunorubicin) HCl is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage, mitophagy and apoptosis in tumor cells. Doxorubicin reduces basal phosphorylation of AMPK. Doxorubicin is used in the concomitant treatment of HIV-infected patients but is found to be at high risk of HBV reactivation.
Targets
AMPK [6]
()
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 Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
L1210 NGjnVHhHfW6ldHnvckBCe3OjeR?= M3jtV2lvcGmkaYTpc44hd2ZiUl7BJJN6dnSqZYPpd{B4cXSqIFXEOVAhd2ZiMD61PEDPxE1? MnyxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwPDlyNUO2K|41QTB3M{[8M4E,
Yoshida sarcoma NE\yVppHfW6ldHnvckBCe3OjeR?= MX7Jcohq[mm2aX;uJI9nKFt|SG3U[HIhcW6lb4Lwc5JifGmxbjD3bZRpKEmFNUCgc4YhOC5yMjFOwG0> M{\HPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF|MkK5PFYoRjF|MkK5PFY9N2F-
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8226/ADR MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX;JR|UxRTBwNU[g{txO NXHNeYhURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUS0O|c{OCd-MUS0O|c{ODxxYU6=
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NCI-SNU-16 NH3wSXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTNzLkG4N|Yh|ryP MkDTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVM1PjNxJ{7TRW5ITVJ:L3G+
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SW684 M3PQemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIHhSm9KSzVyPUO0MlE2PjFizszN M1\WfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU{PDZ|Lze+V2FPT0WUPD;hQi=>
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NCI-H720 NXHNdVY6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnPiTWM2OD12MT65O|I3KM7:TR?= M1nXfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU{PDZ|Lze+V2FPT0WUPD;hQi=>
P31-FUJ MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XZbGlEPTB;NESuN|I5PCEQvF2= NYPFU5lJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTN2NkOvK|5USU6JRWK8M4E,
NCI-H524 NGD3UYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWfJR|UxRTR6LkiyOFgh|ryP NH;SSIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OzR4Mz:nQnNCVkeHUkyvZV4>
Assay
Methods Test Index PMID
Western blot POU5F1 / SOX2 / NANOG ; ATG5 / ATG7 / SQSTM1 / LC3A-II / LC3B-II / p-mTOR ; P62 / LC3II ; p-AKT(T308) / p-Akt(S473) / Akt / p-PRAS40(T246) / PRAS40 / p-H2A.X(S139) 27929731 28208617 26027929
Growth inhibition assay Cell viability 25871400
Immunofluorescence LC3 24970805
ELISA OPN 24963635
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]

Protocol (from reference)

Animal Research:[1]
  • Animal Models: Female athymic nude mice injected s.c. with MB231 cells
  • Dosages: 3 mg/kg/day
  • Administration: Delivered intratumorly
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(172.41 mM)
Water 20 mg/mL
(34.48 mM)
Ethanol 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 Information

Molecular Weight 579.98
Formula

C27H29NO11.HCl

CAS No. 25316-40-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N)O.Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05099666 Not yet recruiting Drug: Lurbinectedin|Drug: Doxorubicin Advanced Soft-tissue Sarcoma|Metastatic Soft-tissue Sarcoma|Advanced Leiomyosarcoma|Leiomyosarcoma Metastatic Massachusetts General Hospital|Jazz Pharmaceuticals March 2022 Phase 1|Phase 2
NCT04968106 Not yet recruiting Drug: Doxorubicin|Drug: Ifosfamide|Drug: INCMGA00012 Retroperitoneal Sarcoma|Resectable Sarcoma Institut Bergonié|Incyte Biosciences International Sàrl February 1 2022 Phase 2
NCT04874311 Recruiting Drug: Bintrafusp alfa|Drug: Doxorubicin Advanced Soft-tissue Sarcoma|Metastatic Soft-tissue Sarcoma Institut Bergonié|Merck Healthcare KGaA Darmstadt Germany an affiliate of Merck KGaA Darmstadt Germany November 1 2021 Phase 2
NCT05100628 Not yet recruiting Drug: NOX66|Drug: Doxorubicin Metastatic Soft-tissue Sarcoma Noxopharm Limited November 15 2021 Phase 1
NCT04423913 Not yet recruiting Other: Administration of embolization beads Prostate Cancer Centre Hospitalier Universitaire de Nīmes October 2021 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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.

Handling Instructions

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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.

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