A3966-10mg | Doxorubicin [23214-92-8] Clinisciences

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.

Product Citation

1. Baiying Lei, et al. "Morphology-based deep learning enables accurate detection of senescence in mesenchymal stem cell cultures." BMC Biol. 2024 Jan 2;22(1):1. PMID: 38167069
2. Meng Wang, Dongfang Xie, et al. "Multiple ingredients of a Chinese medicine formula Sheng-Mai-San coordinately attenuate doxorubicin-induced cardiotoxicity." Pharmacological Research - Modern Chinese Medicine. Volume 8, September 2023, 100281.
3. Riley Plett, Paul Mellor, et al. "Homoharringtonine demonstrates a cytotoxic effect against triple-negative breast cancer cell lines and acts synergistically with paclitaxel." Sci Rep. 2022 Sep 19;12(1):15663. PMID: 36123435
4. Boqin Hu, Dong Zhen, et al. "Ethanol extracts of Rhaponticum uniflorum (L.) DC flowers attenuate doxorubicin-induced cardiotoxicity via alleviating apoptosis and regulating mitochondrial dynamics in H9c2 cells." J Ethnopharmacol. 2022 Apr 24;288:114936. PMID: 35007682
5. Hai-Bing Yang, Zhao-Yang Lu, et al. "Selenium Attenuates Doxorubicin-Induced Cardiotoxicity Through Nrf2-NLRP3 Pathway." Biol Trace Elem Res. 2021 Aug 30. PMID: 34462843
6. Ji Yun Lee, Joo Hyun Kim, et al. "EGR1 as a potential marker of prognosis in extranodal NK/T-cell lymphoma." Sci Rep. 2021 May 14;11(1):10342. PMID: 33990633
7. Zhongying Gong, Xiaoying Liu, et al. "Tumor acidic microenvironment-induced drug release of RGD peptide nanoparticles for cellular uptake and cancer therapy." Colloids Surf B Biointerfaces. 2021 Mar 4;202:111673. PMID: 33714186
8. Ji Yun Lee, Joo Hyun Kim, et al. "Gene Expression Profiling in Extranodal NK/T-Cell Lymphoma." Research Square. December 4th, 2020.
9. Wang X, Wang Q, et al. "TFEB-NF-κB inflammatory signaling axis: a novel therapeutic pathway of Dihydrotanshinone I in doxorubicin-induced cardiotoxicity." J Exp Clin Cancer Res. 2020;39(1):93. PMID: 32448281
10. Gong Z, Lao J, et al. "pH-Triggered geometrical shape switching of a cationic peptide nanoparticle for cellular uptake and drug delivery." Colloids Surf B Biointerfaces. 2020;188:110811. PMID: 31982793
11. Qi W, Boliang W, et al. "Cardamonin protects against doxorubicin-induced cardiotoxicity in mice by restraining oxidative stress and inflammation associated with Nrf2 signaling." Biomed Pharmacother. 2020;122:109547. PMID: 31918264
12. Gong Z, Shi Y, et al. "Plasma Amine Oxidase-Induced Nanoparticle-to-Nanofiber Geometric Transformation of an Amphiphilic Peptide for Drug Encapsulation and Enhanced Bactericidal Activity." ACS Appl Mater Interfaces. 2020;12(4):4323–4332. PMID: 31899611
13. Gong Z, Liu X, Wu J, et al. "pH-triggered morphological change in a self-assembling amphiphilic peptide used as an antitumor drug carrier." Nanotechnology. 2020;31(16):165601. PMID: 31891937
14. Yan L, Ding B, et al. "Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma." Theranostics. 2019 Oct 22;9(26):8377-8391. PMID: 31754403
15. Wang Z, Chen J, et al. "cGAS/STING axis mediates a topoisomerase II inhibitor-induced tumor immunogenicity." J Clin Invest. 2019 Aug 13;130:4850-4862. PMID: 31408442
16. Wang X, Li C, et al. "Tanshinone IIA Restores Dynamic Balance of Autophagosome/Autolysosome in Doxorubicin-Induced Cardiotoxicity via Targeting Beclin1/LAMP1." Cancers (Basel). 2019 Jun 28;11(7). pii: E910. PMID: 31261758
17. Zhang Y, Xia F, et al. "miR-135b-5p enhances doxorubicin-sensitivity of breast cancer cells through targeting anterior gradient 2." J Exp Clin Cancer Res. 2019 Jan 21;38(1):26. PMID: 30665445
18. Goodspeed A, Jean A, et al. "A Whole-genome CRISPR Screen Identifies a Role of MSH2 in Cisplatin-mediated Cell Death in Muscle-invasive Bladder Cancer." Eur Urol. 2019 Feb;75(2):242-250. PMID: 30414698
19. Deng Y, Li F, et al. "Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition." Mol Carcinog. 2018 Jun;57(6):807-814. PMID: 29500880

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Chemical Properties

Physical Appearance	A solid
Storage	Powder: Store at RT; Solution: Store at -20°C
M.Wt	543.52
Cas No.	23214-92-8
Formula	C₂₇H₂₉NO₁₁
Synonyms	Adriamycin, Doxil, Adriablastin, Doxorubicinum, Myocet
Solubility	≥27.2 mg/mL in DMSO; insoluble in EtOH; ≥24.8 mg/mL in H2O with ultrasonic
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
SDF	Download SDF
Canonical SMILES	CC1C(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
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1]:
Cell lines	MDA-MB-231 cells
Preparation method	This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 ℃ for several months.
Reaction Conditions	20 nM; 72 hrs
Applications	In MDA-MB-231 cells, SH003 at 120 μg/mL with Doxorubicin at 20 nM showed a synergistic effect.
Animal experiment [2]:
Animal models	Female athymic nude mice injected s.c. with MB231 cells
Dosage form	3 mg/kg/day; delivered intratumorly
Applications	Doxorubicin in combination with adenoviral MnSOD (AdMnSOD) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) showed the greatest effect in decreasing the volumes of MB231 tumors and prolonging survival of mice.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Woo SM, Kim AJ, Choi YK, Shin YC, Cho SG, Ko SG. Synergistic Effect of SH003 and Doxorubicin in Triple-negative Breast Cancer. Phytother Res. 2016 Aug 1. [2]. Sun W, Kalen AL, Smith BJ, Cullen JJ, Oberley LW. Enhancing the antitumor activity of adriamycin and ionizing radiation. Cancer Res. 2009 May 15;69(10):4294-300.

Biological Activity

Description	Doxorubicin (Adriamycin) is an antibiotic agent, inhibitor of DNA topoisomerase II and inducer of DNA damage and apoptosis.
Targets	Autophagy
IC50