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Chemistry

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Also known as: Daunomycin, 20830-81-3, Acetyladriamycin, Leukaemomycin c, Rubidomycin, Cerubidine
Molecular Formula
C27H29NO10
Molecular Weight
527.5  g/mol
InChI Key
STQGQHZAVUOBTE-VGBVRHCVSA-N
FDA UNII
ZS7284E0ZP

Daunorubicin
A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.
Daunorubicin is an Anthracycline Topoisomerase Inhibitor. The mechanism of action of daunorubicin is as a Topoisomerase Inhibitor.
1 2D Structure

Daunorubicin

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
2.1.2 InChI
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
2.1.3 InChI Key
STQGQHZAVUOBTE-VGBVRHCVSA-N
2.1.4 Canonical SMILES
CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)C)O)N)O
2.1.5 Isomeric SMILES
C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)C)O)N)O
2.2 Other Identifiers
2.2.1 UNII
ZS7284E0ZP
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Cerubidine

2. Dauno Rubidomycine

3. Dauno-rubidomycine

4. Daunoblastin

5. Daunoblastine

6. Daunomycin

7. Daunorubicin Hydrochloride

8. Hydrochloride, Daunorubicin

9. Nsc 82151

10. Nsc-82151

11. Nsc82151

12. Rubidomycin

13. Rubomycin

2.3.2 Depositor-Supplied Synonyms

1. Daunomycin

2. 20830-81-3

3. Acetyladriamycin

4. Leukaemomycin C

5. Rubidomycin

6. Cerubidine

7. (+)-daunomycin

8. Daunoxome

9. Daunorubicinum

10. Daunorubicine

11. Rp 13057

12. Rubomycin C

13. Fi 6339

14. Daunorubicin (inn)

15. Nsc-82151

16. Daunarubicinum

17. Daunorrubicina

18. Daunoxome (tn)

19. Daunamycin

20. Fi-6339

21. Fi6339

22. Rp-13057

23. Zs7284e0zp

24. (7s,9s)-9-acetyl-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione

25. (8s-cis)-8-acetyl-10-((3-amino-2,3,6-trideoxy-alpha-l-lyxo-hexopyrannosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-napthacenedione

26. Chebi:41977

27. Ncgc00024246-05

28. Anthracyline

29. Ndc-0082-4155

30. Dsstox_cid_2883

31. Daunorubicin [inn]

32. Dsstox_rid_76773

33. Dsstox_gsid_22883

34. 5,12-naphthacenedione,8-acetyl-10-[(3-amino-2,3,6-trideoxy-a-l-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8s,10s)-

35. Daunorubicinum [inn-latin]

36. Mls000069508

37. Daunorubicin [inn:ban]

38. Nsc-83142

39. Rcra Waste No. U059

40. (1s,3s)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-l-lyxo-hexopyranoside

41. Cas-20830-81-3

42. Nsc82151

43. Smr000058559

44. Ccris 914

45. Sr-01000000033

46. Sr-05000001600

47. Hsdb 5095

48. Nci-c04693

49. Einecs 244-069-7

50. Nsc 83142

51. Vs-103

52. Brn 1445583

53. Tocris-1467

54. Daunorubicin(daunomycin)

55. Ai3-52942

56. (7s,9s)-9-acetyl-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride

57. Prestwick3_000487

58. Daunomycin [iarc]

59. Daunorubicin [mi]

60. Chembl178

61. Daunorubicin [hsdb]

62. Schembl3041

63. Daunorubicin [vandf]

64. Epirubicin Impurity D

65. Unii-zs7284e0zp

66. Bspbio_000353

67. Daunorubicin [mart.]

68. 5,12-naphthacenedione, 8-acetyl-10-((3-amino-2,3,6-trideoxy-alpha-l-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8s-cis)-

69. Cid_62770

70. Daunorubicin [who-dd]

71. Bpbio1_000389

72. Gtpl7063

73. Dtxsid7022883

74. Bdbm32017

75. Ex-a1337a

76. Valrubicin Impurity, Daunorubicin

77. Daunorubicin [orange Book]

78. Hms2089h04

79. Hms2091k06

80. Pharmakon1600-01500223

81. Vyxeos Component Daunorubicin

82. Zinc3917708

83. Tox21_110896

84. Bdbm50368352

85. Gr-318

86. Hy-13062a

87. Lmpk13050002

88. Mfcd00866340

89. Nsc756717

90. Tox21_110896_1

91. Ccg-212559

92. Cs-2004

93. Db00694

94. Nsc-756717

95. Ncgc00024246-06

96. Ncgc00024246-07

97. Ncgc00024246-09

98. Ncgc00024246-10

99. Ncgc00024246-12

100. Ncgc00024246-15

101. Ncgc00024246-18

102. Ncgc00025173-01

103. (1s,3s)-3-acetyl-3,5,12-trihydroxy-10-(methyloxy)-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-l-lyxo-hexopyranoside

104. (1s,3s)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-a-l-lyxo-hexopyranoside

105. (7s,9r)-9-acetyl-7-[(2s,4s,5s,6s)-4-amino-5-hydroxy-6-methyl-oxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione

106. (7s,9s)-9-acetyl-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione

107. 5,12-naphthacenedione, 8-acetyl-10-((3-amino-2,3,6-trideoxy-alpha-l-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8s,10s)-

108. Sbi-0206677.p002

109. Ab00514669

110. 30d813

111. C01907

112. D07776

113. Epirubicin Hydrochloride Impurity, Daunorubicin-

114. Ab00514669-09

115. Ab01644616_09

116. Ab01644616_10

117. A814957

118. Q411659

119. Sr-01000000033-4

120. Sr-05000001600-1

121. Sr-05000001600-2

122. Brd-k43389675-001-01-3

123. Brd-k43389675-003-02-7

124. Brd-k43389675-003-03-5

125. Brd-k43389675-003-20-9

126. Epirubicin Hydrochloride Impurity D [ep Impurity]

127. Valrubicin Impurity, Daunorubicin [usp Impurity]

128. 2-hydroxy-5-(4-nitro-phenylsulfamoyl)-benzoicacid

129. Doxorubicin Hydrochloride Impurity A [ep Impurity]

130. Epirubicin Hydrochloride Impurity, Daunorubicin- [usp Impurity]

131. (1s,3s)-3-acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-.alpha.-l-lyxo-hexopyranoside

132. (7s,9s)-7-[(2r,4s,5s,6s)-4-azanyl-6-methyl-5-oxidanyl-oxan-2-yl]oxy-9-ethanoyl-4-methoxy-6,9,11-tris(oxidanyl)-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride

133. (7s,9s)-9-acetyl-7-(4-amino-5-hydroxy-6-methyl-tetrahydropyran-2-yl)oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chloride

134. (7s,9s)-9-acetyl-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-quinone;hydrochloride

135. (7s,9s)-9-acetyl-7-[[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyl-2-oxanyl]oxy]-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride

136. (8s,10s)-8-acetyl-10-(((2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyltetrahydro-2h-pyran-2-yl)oxy)-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione

137. (8s,10s)-8-acetyl-10-((3-amino-2,3,6-trideoxy-.alpha.-l-lyxo-hexopyranosyl)oxy)-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione

138. (8s,10s)-8-acetyl-10-{[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione

139. (8s-cis)-8-acetyl-10-[(3-amino-2,3,6-trideoxy-.alpha.-l-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro--6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione

140. 5,12-naphthacenedione, 8-acetyl-10-((3-amino-2,3,6-trideoxy-.alpha.-l-lyxo-hexopyranosyl))oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8s-cis)-

2.4 Create Date
2005-06-24
3 Chemical and Physical Properties
Molecular Weight 527.5 g/mol
Molecular Formula C27H29NO10
XLogP31.8
Hydrogen Bond Donor Count5
Hydrogen Bond Acceptor Count11
Rotatable Bond Count4
Exact Mass527.17914612 g/mol
Monoisotopic Mass527.17914612 g/mol
Topological Polar Surface Area186 Ų
Heavy Atom Count38
Formal Charge0
Complexity960
Isotope Atom Count0
Defined Atom Stereocenter Count6
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 4  
Drug NameCerubidine
PubMed HealthDaunorubicin (Injection)
Drug ClassesAntineoplastic Agent
Active IngredientDaunorubicin hydrochloride
Dosage FormInjectable
RouteInjection
Strengtheq 20mg base/vial
Market StatusPrescription
CompanyEurohlth Intl

2 of 4  
Drug NameDaunoxome
PubMed HealthDaunorubicin Citrate Liposome (Injection)
Drug ClassesAntineoplastic Agent
Active IngredientDaunorubicin citrate
Dosage FormInjectable, liposomal
RouteInjection
Strengtheq 2mg base/ml
Market StatusPrescription
CompanyGalen (uk)

3 of 4  
Drug NameCerubidine
PubMed HealthDaunorubicin (Injection)
Drug ClassesAntineoplastic Agent
Active IngredientDaunorubicin hydrochloride
Dosage FormInjectable
RouteInjection
Strengtheq 20mg base/vial
Market StatusPrescription
CompanyEurohlth Intl

4 of 4  
Drug NameDaunoxome
PubMed HealthDaunorubicin Citrate Liposome (Injection)
Drug ClassesAntineoplastic Agent
Active IngredientDaunorubicin citrate
Dosage FormInjectable, liposomal
RouteInjection
Strengtheq 2mg base/ml
Market StatusPrescription
CompanyGalen (uk)

4.2 Therapeutic Uses

Antibiotics, Antineoplastic

National Library of Medicine's Medical Subject Headings online file (MeSH, 2009)


Cerubidine in combination with other approved anticancer drugs is indicated for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults. /Included in US product label/

US Natl Inst Health; DailyMed. Current Medication Information for Cerubidine (daunorubicin hydrochloride) injection, powder, for solution (November 2007). Available from, as of October 3, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=5821


DaunoXome is indicated as a first line cytotoxic therapy for advanced HIV-associated Kaposi's sarcoma. DaunoXome is not recommended in patients with less than advanced HIV-related Kaposi's sarcoma. /Included in US product label/

US Natl Inst Health; DailyMed. Current Medication Information for Daunoxome (daunorubicin citrate) injection, lipid complex (June 2006). Available from, as of October 3, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=628


An 8-month-old baby with symptoms of Letterer-Siwe's disease responded dramatically after a 5-day course of daunorubicin, 1 mg per kg body-weight daily. A second course was given 2 weeks later.

Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 205


4.3 Drug Warning

Cerubidine must be given into a rapidly flowing intravenous infusion. It must never be given by the intramuscular or subcutaneous route. Severe local tissue necrosis will occur if there is extravasation during administration.

US Natl Inst Health; DailyMed. Current Medication Information for Cerubidine (daunorubicin hydrochloride) injection, powder, for solution (November 2007). Available from, as of October 3, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=5821


Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The incidence of myocardial toxicity increases after a total cumulative dose exceeding 400 to 550 mg/sq m in adults, 300 mg/sq m in children more than 2 years of age, or 10 mg/kg in children less than 2 years of age.

US Natl Inst Health; DailyMed. Current Medication Information for Cerubidine (daunorubicin hydrochloride) injection, powder, for solution (November 2007). Available from, as of October 3, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=5821


Cardiac function should be monitored regularly in patients receiving DaunoXome (daunorubicin citrate liposome injection) because of the potential risk for cardiac toxicity and congestive heart failure. Cardiac monitoring is advised especially in those patients who have received prior anthracyclines or who have pre-existing cardiac disease or who have had prior radiotherapy encompassing the heart.

US Natl Inst Health; DailyMed. Current Medication Information for Daunoxome (daunorubicin citrate) injection, lipid complex (June 2006). Available from, as of October 3, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=628


Severe myelosuppression occurs when used in therapeutic doses; this may lead to infection or hemorrhage.

US Natl Inst Health; DailyMed. Current Medication Information for Cerubidine (daunorubicin hydrochloride) injection, powder, for solution (November 2007). Available from, as of October 3, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=5821


For more Drug Warnings (Complete) data for DAUNORUBICIN (45 total), please visit the HSDB record page.


4.4 Drug Indication

For remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults. Daunorubicin is indicated in combination with [cytarabine] for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Daunorubicin is an anthracycline antibiotic and antineoplastic agent. It acts by inhibiting cellular reproduction through interference with DNA replication although it may contribute to the induction of cell death by increasing oxidative stress through the generation of reactive oxygen species and free radicals. As an antineoplastic agent, daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin also exhibits cardiotoxicity in proportion with the cumulative dose received over time.


5.2 MeSH Pharmacological Classification

Antibiotics, Antineoplastic

Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. (See all compounds classified as Antibiotics, Antineoplastic.)


Topoisomerase II Inhibitors

Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II. (See all compounds classified as Topoisomerase II Inhibitors.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
DAUNORUBICIN
5.3.2 FDA UNII
ZS7284E0ZP
5.3.3 Pharmacological Classes
Mechanisms of Action [MoA] - Topoisomerase Inhibitors
5.4 ATC Code

L01DB02

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01D - Cytotoxic antibiotics and related substances

L01DB - Anthracyclines and related substances

L01DB02 - Daunorubicin


5.5 Absorption, Distribution and Excretion

Absorption

Daunorubicin was found to have a tmax of 2 h and a cmax of 24.8 g/mL after a 90 min infusion of the liposomal formulation at a dose of 44 mg/m2.


Route of Elimination

Daunorubicin is eliminated hepatically. 40% of daunorubicin is excreted in the bile while 25% is excreted in an active form (daunorubicin or daunorubicinol) in the urine. In the liposomal formulation, only 9% of active molecules are excreted in the urine.


Volume of Distribution

Daunorubicin has a steady-state volume of distribution of 1.91 L/m2 reported with the liposomal formulation. The average volume of distribution reported for the liposomal formulation is 6.6 L.


Clearance

Daunorubicin has a clearance of 68.4 mL/h/m2 determined using the liposomal formulation.


Note: Liposomal encapsulation can substantially affect a drug's functional properties relative to those of the unencapsulated drug. In addition, different liposomal drug products may vary from one another in the chemical composition and physical form of the liposomes. Such differences can substantially affect the functional properties of liposomal drug products.

US Natl Inst Health; DailyMed. Current Medication Information for Daunoxome (daunorubicin citrate) injection, lipid complex (June 2006). Available from, as of October 3, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=628


Encapsulation of daunorubicin citrate in liposomes substantially alters the pharmacokinetics of the drug relative to conventional iv formulations (ie, nonencapsulated drug) with resultant decreased distribution into the peripheral compartment, increased distribution into Kaposi's lesions, and decreased plasma clearance

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)


Daunorubicin hydrochloride is extremely irritating to tissues and, therefore, must be administered iv. Following iv infusion of a single 40-mg/sq m dose of liposomal daunorubicin citrate as a liposomal injection in patients with AIDS-related Kaposi's sarcoma, mean peak plasma daunorubicin (mostly bound to liposomes) concentrations are approximately 18 mug/mL following a 30-60 minute infusion. Peak plasma concentrations of daunorubicin are higher following iv administration of liposomal daunorubicin citrate than those attained following iv administration of conventional (nonencapsulated) daunorubicin hydrochloride.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)


In one study in patients with disseminated malignancies receiving a single 80-mg/sq m iv dose of nonencapsulated daunorubicin, peak plasma concentrations of the drug were 0.4 ug/mL while in patients with solid tumors (including those with Kaposi's sarcoma) who received a single 80-mg/sq m iv dose of liposomal daunorubicin, peak plasma concentrations of daunorubicin were about 44 ug/mL (about 100-fold greater than those receiving a comparable dose of the nonencapsulated drug); area under the plasma concentration-time curve (AUC) was about 36-fold greater than that observed with conventional daunorubicin hydrochloride. Following iv administration of liposomal daunorubicin, peak plasma concentrations and AUCs of daunorubicin generally increase linearly with increasing doses (at doses of 10-80 ug/mL).

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)


For more Absorption, Distribution and Excretion (Complete) data for DAUNORUBICIN (18 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Daunorubicin hydrochloride is extensively metabolized in the liver and other tissues, mainly by cytoplasmic aldo-keto reductases, producing daunorubicinol, the major metabolite which has antineoplastic activity. Approximately 40% of the drug in the plasma is present as daunorubicinol within 30 minutes and 60% in 4 hours after a dose of nonencapsulated daunorubicin.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)


Daunorubicinol has been detected only in low concentrations in the plasma following iv administration of daunorubicin citrate liposomal injection. In patients with AIDS-associated Kaposi's sarcoma receiving iv administration of liposomal daunorubicin doses of 40 mg/sq m, the AUC of daunorubicinol represented only 2% of the total daunorubicin AUC. Additional metabolism by reductive cleavage of the glycosidic bond produces aglycones, which have little or no cytotoxic activity and are demethylated and conjugated with sulfate and glucuronide by microsomal enzymes.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)


Metabolites identified in human urine are daunorubicinol, daunorubicinol aglycone, desmethyldeoxydaunorubicinol aglycone, desmethyldeoxyrubicinol aglycone-4-o-sulfate, desmethyloxydaunorubicinol aglycone-4-o-glucuronide, and deoxydaunorubicinol aglycone glucuronide.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V10 150 (1976)


Extensively metabolized, initially to active alcohol metabolites; further metabolized by liver microsomes to inactive aglycones and demethylated glucuronide and sulfate conjugates.

Knoben, J.E. and P.O. Anderson (eds.) Handbook of Clinical Drug Data. 6th ed. Bethesda, MD: Drug Intelligence Publications, Inc. 1988., p. 401


5.7 Biological Half-Life

Daunorubicin has been determined to have a terminal half-life of 18.5 h (+/- 4.9). Daunorubicinol, the primary active metabolite has been determined to have a terminal half-life of 26.7 h (+/- 12.8). The mean half-life of elimination of liposomal daunorubicin has been reported to be 22.1 h in pharmacokinetic studies and 31.5 h in official FDA labeling.


Following rapid iv administration of conventional daunorubicin hydrochloride injection, total plasma concentrations of daunorubicin and its metabolites decline in a triphasic manner, and plasma concentrations of unchanged daunorubicin decline in a biphasic manner.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)


The plasma half-life of nonencapsulated daunorubicin averages 45 minutes in the initial phase and 18.5 hours in the terminal phase. By 1 hour after administration of nonencapsulated daunorubicin, the predominant form of the drug in plasma is the active metabolite daunorubicinol, which has an average terminal plasma half-life of 26.7 hours.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)


The apparent elimination half-life of DaunoXome (daunorubicin citrate liposome injection) is 4.4 hours, far shorter than that of daunorubicin, and probably represents a distribution half-life.

US Natl Inst Health; DailyMed. Current Medication Information for Daunoxome (daunorubicin citrate) injection, lipid complex (June 2006). Available from, as of October 3, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=628


5.8 Mechanism of Action

Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin 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.


Daunorubicin is an antineoplastic antibiotic. Daunorubicin has antimitotic and cytotoxic activity. Daunorubicin forms a complex with DNA by intercalation between base pairs. By stabilizing the complex between DNA and topoisomerase II, daunorubicin inhibits the activity of this enzyme, resulting in single-strand and double-strand breaks in DNA. Daunorubicin also may inhibit polymerase activity, affect regulation of gene expression, and be involved in free radical damage to DNA. Although daunorubicin is maximally cytotoxic in the S phase, the drug is not cycle-phase specific. Daunorubicin also has antibacterial and immunosuppressive properties.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)


Anthracyclines are an important reagent in many chemotherapy regimes for treating a wide range of tumors. One of the primary mechanisms of anthracycline action involves DNA damage caused by inhibition of topoisomerase II. Enzymatic detoxification of anthracycline is a major critical factor that determines anthracycline resistance. Natural product, daunorubicin a toxic analogue of anthracycline is reduced to less toxic daunorubicinol by the AKR1B10, enzyme, which is overexpressed in most cases of smoking associate squamous cell carcinoma (SCC) and adenocarcinoma. In addition, AKR1B10 was discovered as an enzyme overexpressed in human liver, cervical and endometrial cancer cases in samples from uterine cancer patients. Also, the expression of AKR1B10 was associated with tumor recurrence after surgery and keratinization of squamous cell carcinoma in cervical cancer and estimated to have the potential as a tumor intervention target colorectal cancer cells (HCT-8) and diagnostic marker for non-small-cell lung cancer. This article presents the mechanism of daunorubicin action and a method to improve the effectiveness of daunorubicin by modulating the activity of AKR1B10.

PMID:19442055 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205813 Balendiran GK; Curr Cancer Drug Targets 9 (3): 366-9 (2009).


... In the present study using the ATP depleting agents cyanide, azide, or dinitrophenol to inhibit energy dependent transport processes, /investigators/ observed even larger increases in daunorubicin accumulation than were seen with CsA. Similar patterns were seen in a wide range of P-gp negative human cancer cell lines. Also the observed cyanide effect did not correlate with the expression of mRNA for multidrug resistance-associated protein (MRP), the only other member of the ABC family of membrane transporters that is known to be capable of effluxing daunorubicin. Thse results suggest that daunorubicin accumulation in many cases of AML is modulated by one or more novel energy-dependent processes that are distinct from P-gp or MRP. /The authors/ speculate that this novel drug transport mechanism(s) may influence the response of AML patients to daunorubicin and other therapeutic agents.

PMID:9001418 Hedley DW et al; Leukemia 11 (1): 48-53 (1997).


Inhibits DNA synthesis and blocks DNA-directed RNA polymerase. It can prevent cell division in doses that do not interfere with nucleic acid synthesis.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1086


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01

Brand Name : Cerubidin

France
arrow
Medlab Asia & Asia Health
Not Confirmed
  • fda
  • EDQM
  • WHO-GMP

Virtual BoothSanofi is a pioneer in Diabetes Solutions, Human Vaccines, Innovative Drugs, Consumer Healthcare, and the new Genzyme.

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Digital Content Digital Content

RX/OTC/DISCN :

Daunorubicin

Dosage Form : Powder for infusion fluid, resol...

Dosage Strength : 20 mg

Price Per Pack (Euro) : 314.12

Published in :

Country : Norway

RX/OTC/DISCN :

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02

Brand Name : Daunoblastina

U.S.A
arrow
Medlab Asia & Asia Health
Not Confirmed

Brand Name : Daunoblastina

U.S.A
arrow
Medlab Asia & Asia Health
Not Confirmed

Daunorubicin

Dosage Form : Daunorubicin 20Mg 10Ml 1 Units P...

Dosage Strength : 1 vial EV 20 mg + 1 ampoule solv 10 ml

Price Per Pack (Euro) : 19.5

Published in :

Country : Italy

RX/OTC/DISCN : Class H

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03

Brand Name : Cerubidine

Denmark
arrow
Medlab Asia & Asia Health
Not Confirmed

Brand Name : Cerubidine

Denmark
arrow
Medlab Asia & Asia Health
Not Confirmed

Daunorubicin

Dosage Form : Powder for infusion fluid, resol...

Dosage Strength : 20 mg

Price Per Pack (Euro) : 314.12

Published in :

Country : Norway

RX/OTC/DISCN :

blank

04

Brand Name : Daunoblastin

U.S.A
arrow
Medlab Asia & Asia Health
Not Confirmed

Brand Name : Daunoblastin

U.S.A
arrow
Medlab Asia & Asia Health
Not Confirmed

Daunorubicin

Dosage Form : Trockensub

Dosage Strength : 20mg

Price Per Pack (Euro) : 31.1

Published in :

Country : Switzerland

RX/OTC/DISCN : Class A

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