Daunorubicin
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| Systematic (IUPAC) name | |
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(8S,10S)-8-acetyl-10-[(2S,4S,5S,6S)-
4-amino-5-hydroxy-6-methyl-oxan- 2-yl]oxy-6,8,11-trihydroxy-1-methoxy- 9,10-dihydro-7H-tetracene-5,12-dione |
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| Clinical data | |
| Trade names | Cerubidine |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a682289 |
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| Routes of administration |
Exclusively intravenous. Causes severe necrosis if administered intramuscularly or subcutaneously |
| Pharmacokinetic data | |
| Metabolism | Hepatic |
| Biological half-life | 26.7 hours (metabolite) |
| Excretion | Biliary and urinary |
| Identifiers | |
| CAS Number | 20830-81-3  |
| ATC code | L01DB02 (WHO) |
| PubChem | CID: 30323 |
| IUPHAR/BPS | 7063 |
| DrugBank | DB00694 |
| ChemSpider | 28163 |
| UNII | ZS7284E0ZP |
| KEGG | C01907 |
| ChEBI | CHEBI:41977 |
| ChEMBL | CHEMBL178 |
| Chemical data | |
| Formula | C27H29NO10 |
| Molecular mass | 527.52 g/mol 563.99 g/mol (HCl salt) |
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Daunorubicin or daunomycin (trade name Cerubidine) is chemotherapeutic of the anthracycline family that is given as a treatment for some types of cancer. It is most commonly used to treat specific types of leukemia (acute myeloid leukemia and acute lymphocytic leukemia). It was initially isolated from Streptomyces peucetius.
A liposomal formulation of daunorubicin, liposomal daunorubicin, is marketed in the United States as DaunoXome.
It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[1]
Contents
Medical uses
It slows or stops the growth of cancer cells in the body. Treatment is usually performed together with other chemotherapy drugs (such as cytarabine), and its administration depends on the type of tumor and the degree of response.
In addition to its major use in treating AML, daunorubicin is also used to treat neuroblastoma. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of chronic myelogenous leukemia.
Daunorubicin is also used as the starting material for semi-synthetic manufacturing of doxorubicin, epirubicin and idarubicin.
Mechanism of action
Similar to doxorubicin, daunorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis.[2][3] This inhibits the progression of the enzyme topoisomerase II, which relaxes supercoils in DNA for transcription. Daunorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. On binding to DNA, daunomycin intercalates, with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C base pairs flanked on the 5' side by an A/T base pair. Daunomycin effectively binds to every 3 base pairs and induces a local unwinding angle of 8°, but negligible distortion of helical conformation.[4] It can also induce histone eviction from chromatin upon intercalation.[5][6]
History
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In the 1950s, an Italian research company, Farmitalia Research Laboratories, began an organized effort to isolate anticancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th-century castle in Apulia. A new strain of Streptomyces peucetius which produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against murine tumors. Since a group of French researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name Dauni, a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby, rubis, describing the color.[7][8][9] Clinical trials began in the 1960s, and the drug saw success in treating acute leukemia and lymphoma.
However, by 1967, it was recognized that daunorubicin could produce fatal cardiac toxicity.[10]
In 2015-16, a team at Ohio State University "showed that, by carefully manipulating strands of viral DNA, an origami structure with complex folds can be created in just 10 minutes. Incredibly, these structures are only 100 nanometers across – that’s 1,000 times smaller than the width of a human hair. Small volumes of daunorubicin can be wrapped up in these minuscule pods, which can then be released into a leukemia cell-filled environment." http://www.iflscience.com/health-and-medicine/researchers-kill-drug-resistant-leukemia-cells-using-dna-trojan-horse-attack
Route of administration
Daunorubicin should only be administered in a rapid intravenous infusion. It should not be administered intramuscularly or subcutaneously, since it may cause extensive tissue necrosis. It should also never be administered intrathecally (into the spinal canal), as this will cause extensive damage to the nervous system and may lead to death. Daunorubicin has been used intravitreally (inside the eye) for the purposes of preventing proliferative vitreoretinopathy, a common complication following retinal detachment surgery, but has not been found to be effective and is not used for any other ophthalmic purposes at this time.[11]
See also
References
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- ↑ Baruffa G. Clinical trials in Plasmodium falciparum malaria with a long-acting sulphonamide. Trans R Soc Trop Med Hyg. 1966;60(2):222-4. PMID 5332105
- ↑ Per prior citation, the first publication: Camerino B, Palamidessi G (1960) Derivati della parazina II. Sulfonamdopir (in Italian). Gazz Chim Ital 90:1802–1815
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
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