Definition
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
Description
Doxorubicin is only found in individuals that have used or taken this drug. It is antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of daunorubicin. [PubChem]Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged. Two electron reduction yields doxorubicinol, a secondary alcohol. This pathway is considered the primary metabolic pathway. The one electron reduction is facilitated by several oxidoreductases to form a doxirubicin-semiquinone radical. These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases. Deglycosidation is a minor metabolic pathway (1-2% of the dose undergoes this pathway). The resultant metabolites are deoxyaglycone or hydroxyaglycone formed via reduction or hydrolysis respectively. Enzymes that may be involved with this pathway include xanthine oxidase, NADPH-cytochrome P450 reductase, and cytosolic NADPH dehydrogenase. Route of Elimination: 40% of the dose appears in bile in 5 days. 5-12% of the drug and its metabolites appears in urine during the same time period. <3% of the dose recovered in urine was doxorubicinol. Half Life: Terminal half life = 20 - 48 hours.
- Uses/Sources: Doxorubicin is used to produce regression in disseminated neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms' tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin's disease, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.
- Health Effects: Antibiotic resistance
- Symptoms: The most common side effects from antibiotics are diarrhea, nausea, vomiting. Fungal infections of the mouth, digestive tract and vagina can also occur with antibiotics
- Treatment: Treatment of acute overdosage consists of treatment of the severely myelosuppressed patient with hospitalization, antibiotics, platelet and granulocyte transfusions, and symptomatic treatment of mucositis. (L1712)
- Route of Exposure: Parenteral (intravenous)
Toxicity
- Carcinogenicity: 2A, probably carcinogenic to humans. (L135)
- Toxicity: LD50: 21 800 ug/kg (Subcutaneous, Rat) (A308)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
DNA topoisomerase 2-alpha | Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. |
17016621 11752352 11430001 17010609 17089011 17351394 17578914 |
DNA Multidrug resistance-associated protein 1 Solute carrier organic anion transporter family member 1B1 DNA topoisomerase 1 72 kDa type IV collagenase Aurora kinase A Solute carrier organic anion transporter family member 2B1 Solute carrier organic anion transporter family member 1B3 Telomerase reverse transcriptase 7-dehydrocholesterol reductase P2Y purinoceptor 12 Fas-binding factor 1 Nucleolar and coiled-body phosphoprotein 1 |
1277199 19463000 22541068 8183243 11430001 8621644 21664013 17378599 1322986 15588086 17129415 20662543 2334681 |