Daunorubicin

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Daunorubicin
Clinical data
Trade namesCerubidine, others
AHFS/Drugs.comMonograph
MedlinePlusa682289
Pregnancy
category
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver
Elimination half-life26.7 hours (metabolite)
ExcretionBile duct and urinary
Identifiers
  • (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
JSmol)
  • C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](Cc3c2c(c4c(c3O)C(=O)c5cccc(c5C4=O)OC)O)(C(=O)C)O)N)O
  • InChI=1S/C27H29NO10/c1-10-22(30)14(28)7-17(37-10)38-16-9-27(35,11(2)29)8-13-19(16)26(34)21-20(24(13)32)23(31)12-5-4-6-15(36-3)18(12)25(21)33/h4-6,10,14,16-17,22,30,32,34-35H,7-9,28H2,1-3H3/t10-,14-,16-,17-,22+,27-/m0/s1 checkY
  • Key:STQGQHZAVUOBTE-VGBVRHCVSA-N checkY
  (verify)

Daunorubicin, also known as daunomycin, is a

liposomal formulation known as liposomal daunorubicin also exists.[2]

Common side effects include hair loss, vomiting,

topoisomerase II.[2]

Daunorubicin was approved for medical use in the United States in 1979.[2] It is on the World Health Organization's List of Essential Medicines.[4] It was originally isolated from bacteria of the Streptomyces type.[5]

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.[citation needed]

In addition to its major use in treating acute myeloid leukemia, daunorubicin is also used to treat neuroblastoma. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of chronic myelogenous leukemia.[citation needed]

Daunorubicin is also used as the starting material for semi-synthetic manufacturing of doxorubicin, epirubicin and idarubicin.[citation needed]

Mechanism of action

Similar to

transcription of DNA. 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. Crystallography shows that daunomycin induces a local unwinding angle of 8°, and other conformational disturbances of adjacent and second-neighbour base pairs.[8] It can also induce histone eviction from chromatin upon intercalation.[9][10]

History

See also: Anthracycline § History, Doxorubicin § History, and History of cancer chemotherapy

In the 1950s, an

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.[11][12][13]
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.[14]

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."[15][unreliable medical source?]

Route of administration

Daunorubicin should only be administered in a rapid

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.[16]

References

  1. ^ "Daunorubicin (Cerubidine) Use During Pregnancy". Drugs.com. 19 September 2019. Retrieved 15 August 2020.
  2. ^ a b c d e f g h i "Daunorubicin hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 8 January 2017. Retrieved 8 December 2016.
  3. ISBN 9780857111562
    .
  4. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  5. ISBN 9781118075630. Archived
    from the original on 21 December 2016.
  6. PMID 8183243
    .
  7. PMID 1277199. Archived
    from the original on 5 February 2009.
  8. PMID 6938965
    .
  9. PMID 23715267
    .
  10. PMID 25961671
    .
  11. PMID 1462166
    .
  12. PMID 5332105
    .
  13. ^ Camerino B, Palamidessi G (1960). "Derivati della parazina II. Sulfonamdopir" [Derivatives of parazine II. Sulfonamdopir]. Gazzetta Chimica Italiana [Italian Chemical Journal] (in Italian). 90: 1802–1815.
  14. S2CID 19272219
    .
  15. ^ "Researchers kill drug-resistant leukemia cells using DNA Trojan horse attack". IFL Science. 25 February 2016.
  16. PMID 1574039
    .
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