Daunorubicin


Daunorubicin
Daunorubicin
Systematic (IUPAC) name
(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
Clinical data
Trade names Cerubidine
AHFS/Drugs.com monograph
MedlinePlus a682289
Pregnancy cat. D (U.S.)
Legal status  ?
Routes Exclusively intravenous. Causes severe necrosis if administered intramuscularly or subcutaneously
Pharmacokinetic data
Metabolism Hepatic
Half-life 26.7 hours (metabolite)
Excretion Biliary and urinary
Identifiers
CAS number 20830-81-3 YesY
ATC code L01DB02
PubChem CID 30323
DrugBank APRD00521
ChemSpider 28163 YesY
UNII ZS7284E0ZP YesY
KEGG C01907 YesY
ChEBI CHEBI:41977 YesY
ChEMBL CHEMBL178 YesY
Chemical data
Formula C27H29NO10 
Mol. mass 527.52 g/mol
563.99 g/mol (HCl salt)
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Daunorubicin or daunomycin (daunomycin 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 leukaemia (acute myeloid leukemia and acute lymphocytic leukemia). It was initially isolated from Streptomyces peucetius.

A liposomal formulation of daunorubicin is marketed in the United States as DaunoXome.

Contents

History

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.[1] 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.[2]

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.

Mode of action

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 11o, but negligible distortion of helical conformation.[citation needed]

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.[3]

References

  1. ^ Weiss RB (December 1992). "The anthracyclines: will we ever find a better doxorubicin?". Seminars in Oncology 19 (6): 670–86. PMID 1462166. 
  2. ^ Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA (March 1967). "Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia". Cancer 20 (3): 333–53. doi:10.1002/1097-0142(1967)20:3<333::AID-CNCR2820200302>3.0.CO;2-K. PMID 4290058. 
  3. ^ Mortensen, ME et al. (1992). "Inadvertent intrathecal injection of daunorubicin with fatal outcome". Med Pediatr Oncol 20 (3): 249–253. PMID 1574039. 

External links