Doxorubicin
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.
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| Physical Appearance | A solid |
| Storage | Store at 4°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. |
| Cell experiment [1]: | |
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Cell lines |
MDA-MB-231 cells |
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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. |
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Reaction Conditions |
20 nM; 72 hrs |
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Applications |
In MDA-MB-231 cells, SH003 at 120 μg/mL with Doxorubicin at 20 nM showed a synergistic effect. |
| Animal experiment [2]: | |
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Animal models |
Female athymic nude mice injected s.c. with MB231 cells |
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Dosage form |
3 mg/kg/day; delivered intratumorly |
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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. |
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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. |
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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. |
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| Description | Doxorubicin (Adriamycin) is an antibiotic agent, inhibitor of DNA topoisomerase II and inducer of DNA damage and apoptosis. | |||||
| Targets | Autophagy | |||||
| IC50 | ||||||
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