Identification

Name
Daunorubicin
Accession Number
DB00694  (APRD00521)
Type
Small Molecule
Groups
Approved
Description

A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of leukemia and other neoplasms. [PubChem]

Structure
Thumb
Synonyms
  • (+)-Daunomycin
  • (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
  • Acetyladriamycin
  • Daunomycin
  • Daunorubicin
  • Daunorubicina
  • Daunorubicine
  • Daunorubicinum
  • Leukaemomycin C
  • Rubidomycin
External IDs
DNR / FI 6339 / NSC 82151 / RCRA Waste No. U059 / RP 13057
Product Ingredients
IngredientUNIICASInChI Key
Daunorubicin citrate5L84T2Z6NP371770-68-2VNTHYLVDGVBPOU-QQYBVWGSSA-N
Daunorubicin HydrochlorideUD984I04LZ23541-50-6GUGHGUXZJWAIAS-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cerubidine 20mg/vialPowder, for solution20 mgIntravenousErfa Canada 2012 Inc1971-12-31Not applicableCanada
Daunorubicin HydrochlorideInjection5 mg/1mLIntravenousWest-Ward Pharmaceuticals Corp2018-01-02Not applicableUs
Daunorubicin HydrochlorideInjection5 mg/1mLIntravenousWest-Ward Pharmaceuticals Corp2018-01-02Not applicableUs
Daunorubicin Hydrochloride for InjectionPowder, for solution20 mgIntravenousTeva1998-03-04Not applicableCanada
DaunoXomeInjection, lipid complex2 mg/1mLIntravenousGilead Sciences1996-04-082011-07-01Us
DaunoXomeInjection, lipid complex2 mg/1mLIntravenousGalen US Inc2012-02-132016-04-16Us
Daunoxome Liposomal - IV 2mg/ml, 50mg/vialSuspension2 mgIntravenousGilead Sciences1997-09-222001-09-21Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CerubidineInjection, powder, for solution20 mg/4mLIntravenousBedford Pharmaceuticals1998-06-012013-09-30Us
Daunorubicin HydrochlorideInjection, solution5 mg/1mLIntravenousBedford Pharmaceuticals1998-07-132012-10-31Us
Daunorubicin HydrochlorideInjection, solution5 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2004-04-01Not applicableUs
Daunorubicin HydrochlorideInjection5 mg/1mLIntravenousBedford Pharmaceuticals1998-06-012013-09-30Us
Daunorubicin HydrochlorideInjection, powder, lyophilized, for solution5 mg/1mLIntravenousBedford Pharmaceuticals1996-06-282013-04-30Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
VyxeosDaunorubicin (44 mg/20mL) + Cytarabine (100 mg/20mL)Injection, powder, lyophilized, for suspensionIntravenousJazz Pharmaceuticals, Inc.2017-08-03Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Daunorubicin HydrochlorideDaunorubicin Hydrochloride (20 mg/4mL)Injection, powder, for solutionIntravenousHalison Pharmaceuiticals Usa, Inc2016-10-01Not applicableUs
International/Other Brands
Cerubidin (Sanofi-Aventis) / Cerubidine (Sanofi-Aventis) / Cérubidine (Sanofi-Aventis) / Daunoblastin (Pfizer) / Daunoblastina (Pfizer) / Daunorrubicina (GP-Pharm) / Maxidauno (Varifarma)
Categories
UNII
ZS7284E0ZP
CAS number
20830-81-3
Weight
Average: 527.5199
Monoisotopic: 527.179146153
Chemical Formula
C27H29NO10
InChI Key
STQGQHZAVUOBTE-VGBVRHCVSA-N
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
IUPAC Name
(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
SMILES
COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(C)=O)C(O)=C1C2=O

Pharmacology

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.

Associated Conditions
Pharmacodynamics

Daunorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Daunorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Daunorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.

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.

TargetActionsOrganism
ADNA
intercalation
Human
ADNA topoisomerase 2-alpha
inhibitor
Human
ADNA topoisomerase 2-beta
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

97% binding-albumin

Metabolism

Hepatic

Route of elimination

Twenty-five percent of an administered dose of daunorubicin hydrochloride is eliminated in an active form by urinary excretion and an estimated 40% by biliary excretion.

Half life

18.5 hours

Clearance
Not Available
Toxicity

LD50=20 mg/kg (mice, IV); LD50=13 mg/kg (rat, IV)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 1B1---(G;G) / (C;G)G alleleADR Directly StudiedThe presence of this genotype in CYP1B1 may be associated with an increased risk of drug-induced cytotoxicity from daunorubicin therapy.Details
Heterogeneous nuclear ribonucleoprotein D0---(A;A) / (A;G)A alleleADR Directly StudiedThe presence of this genotype in HNRNPD may be associated with an increased risk of drug-induced cytotoxicity from daunorubicin therapy.Details
SEC14-like protein 3---(T;T) / (G;T)T alleleADR Directly StudiedThe presence of this genotype in SEC14L3 may be associated with an increased risk of drug-induced cytotoxicity from daunorubicin therapy.Details
Inhibitor of nuclear factor kappa-B kinase subunit epsilon---(A;A) / (A;G)A alleleADR Directly StudiedThe presence of this genotype in IKBKE may be associated with an increased risk of drug-induced cytotoxicity from daunorubicin therapy.Details
Retinoic acid receptor gamma---(C;C) / (C;T)C>TADR Directly StudiedPediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with daunorubicin.Details
Solute carrier family 28 member 3---(A;A) / (A;G)G > AADR Directly StudiedPediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with daunorubicin.Details
UDP-glucuronosyltransferase 1-6UGT1A6*4(T;T) / (G;T)G > TADR Directly StudiedPediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with daunorubicin.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Daunorubicin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Daunorubicin.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Daunorubicin.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Daunorubicin is combined with 2-Methoxyethanol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Daunorubicin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Daunorubicin.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Daunorubicin.
6-Deoxyerythronolide BThe metabolism of Daunorubicin can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Daunorubicin.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Daunorubicin is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
Food Interactions
Not Available

References

Synthesis Reference

Sylvie Pinnert, Leon Ninet, Jean Preud'Homme, "Antibiotic daunorubicin and its preparation." U.S. Patent US3989598, issued March, 1965.

US3989598
General References
Not Available
External Links
Human Metabolome Database
HMDB0014832
KEGG Compound
C01907
PubChem Compound
30323
PubChem Substance
46508433
ChemSpider
28163
BindingDB
32017
ChEBI
41977
ChEMBL
CHEMBL178
Therapeutic Targets Database
DNC000517
PharmGKB
PA449212
HET
DM1
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Daunorubicin
ATC Codes
L01DB02 — Daunorubicin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
110d / 152d / 1d10 / 1d11 / 1d33 / 1da0 / 1jo2 / 1o0k / 1vth / 1vti
show 6 more
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentAcute, recurrent Myeloid Leukemia / CD33 Positive / High Risk Myelodysplastic Syndrome / Refractory Acute Myeloid Leukemia1
0Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1Active Not RecruitingTreatmentAML Arising After Exposure to Genotoxic Injury / AML Arising From Antecedent Hematologic Disorder (AHD) / AML Arising From Myelodysplastic Syndrome (MDS) / Newly Diagnosed Acute Myeloid Leukemia (AML) / Untreated AML1
1Active Not RecruitingTreatmentAdvanced Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML)1
1Active Not RecruitingTreatmentBlasts 10-19 Percent of Bone Marrow Nucleated Cells / Blasts 20 Percent or More of Bone Marrow Nucleated Cells / Blasts 5-19 Percent of Peripheral Blood White Cells / Blasts More Than 10 Percent of Bone Marrow Nucleated Cells / Chronic Myelomonocytic Leukemia-2 / High Risk Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Myeloproliferative Neoplasms / Previously Treated Myelodysplastic Syndromes / Untreated Adult Acute Myeloid Leukemia1
1Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Leukemias1
1Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Malignancies, Hematologic1
1CompletedTreatmentAcute Myelogenous Leukaemia (AML)1
1CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Leukemia Acute Myeloid Leukemia (AML)1
1CompletedTreatmentAcute, secondary Myeloid Leukemia / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Untreated Adult Acute Myeloid Leukemia1
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)3
1CompletedTreatmentLeukemias3
1Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphocytic Leukemia (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Malignancies, Hematologic / Myelodysplastic Syndromes1
1Not Yet RecruitingTreatmentMyelodysplastic Syndromes1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Leukemia Acute Myeloid Leukemia (AML)1
1RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)4
1SuspendedTreatmentAcute, secondary Myeloid Leukemia / Recurrent Adult Acute Myeloid Leukemia / Therapy-Related Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
1TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1TerminatedTreatmentLeukemias1
1TerminatedTreatmentSarcomas1
1Unknown StatusTreatmentLeukemias1
1WithdrawnTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2CompletedTreatmentAcute Undifferentiated Leukemia (AUL) / B-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / L1 Adult Acute Lymphoblastic Leukemia / L1 Childhood Acute Lymphoblastic Leukemia / L2 Adult Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia / Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia / T-cell Adult Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
1, 2CompletedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentChronic Myelomonocytic Leukemia / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2CompletedTreatmentLeukemias4
1, 2CompletedTreatmentMyeloid Leukemias1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2RecruitingTreatmentPreviously Untreated Acute Myeloid Leukemia1
1, 2SuspendedTreatmentAcute, secondary Myeloid Leukemia / Blasts 5 Percent or More of Bone Marrow Nucleated Cells / Recurrent Childhood Acute Myeloid Leukemia / Therapy-Related Acute Myeloid Leukemia1
1, 2TerminatedTreatmentChronic Myeloid Leukemia (CML)1
1, 2WithdrawnTreatmentUntreated Adult Acute Myeloid Leukemia1
2Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Untreated Adult Acute Lymphoblastic Leukemia1
2Active Not RecruitingTreatmentAcute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13.3;q13.1); RBM15-MKL1 / Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13.3;q13.3); RBM15-MKL1 / Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13;q13); RBM15-MKL1 / Acute Myeloid Leukemia With a Variant RARA Translocation / Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2) or t(3;3) (q21.3;q26.2); GATA2, MECOM / Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 / Acute Myeloid Leukemia With t(6;9) (p23;q34.1); DEK-NUP214 / Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214 / Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3); MLLT3-KMT2A / Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A / Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Acute Myeloid Leukemia With Variant MLL Translocations / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
2Active Not RecruitingTreatmentAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Acute, secondary Myeloid Leukemia / Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 / Core Binding Factor Acute Myeloid Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Therapy-Related Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2Active Not RecruitingTreatmentAcute Myeloid Leukemia With Myelodysplasia-Related Changes / Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A / Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
2Active Not RecruitingTreatmentAcute, secondary Myeloid Leukemia / Adult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Monoblastic Leukemia / Adult Acute Monocytic Leukemia / Adult Acute Myeloid Leukemia With Maturation / Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A / Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Adult Acute Myeloid Leukemia Without Maturation / Adult Acute Myelomonocytic Leukemia / Alkylating Agent-Related Acute Myeloid Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
2Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)3
2Active Not RecruitingTreatmentLeukemias1
2Active Not RecruitingTreatmentLymphoma, Lymphoblastic1
2Active Not RecruitingTreatmentNewly Diagnosed AML With FLT3 Activating Mutations1
2Active Not RecruitingTreatmentUntreated Adult Acute Myeloid Leukemia1
2CompletedNot AvailableAcute Myelogenous Leukaemia (AML)1
2CompletedBasic ScienceLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes / Myeloproliferative Neoplasms / Myeloproliferative/Myelodysplastic Neoplasm1
2CompletedSupportive CareAnemias / Leukemias / Neutropenias / Thrombocytopenias1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)2
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL)1
2CompletedTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Acute, secondary Myeloid Leukemia / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentLeukaemia, Lymphoblastic / Lymphoma, Lymphoblastic1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)3
2CompletedTreatmentLeukemia, Acute1
2CompletedTreatmentLeukemias15
2CompletedTreatmentLeukemias / Malignant Lymphomas2
2CompletedTreatmentLeukemias / Neutropenias / Thrombocytopenias1
2CompletedTreatmentMalignant Lymphomas2
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Enrolling by InvitationTreatmentAcute,Leukemia, Lymphoid1
2RecruitingTreatmentAcute Leukemias of Ambiguous Lineage / Childhood B Acute Lymphoblastic Leukemia / KMT2A Gene Rearrangement / Mixed Phenotype Acute Leukemia (MPAL)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemia Recurrent / Acute Lymphoblastic Leukaemias (ALL) / Leukemia, Lymphocytic / Refractory Acute Lymphoblastic Leukemia1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Childhood Cancers / Down Syndrome (DS)1
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Adult Lymphoblastic Lymphoma1
2RecruitingTreatmentAcute, secondary Myeloid Leukemia / Adult Acute Myeloid Leukemia / Adult Myelodysplastic Syndrome / Therapy-Related Acute Myeloid Leukemia1
2RecruitingTreatmentAll1
2RecruitingTreatmentLeukaemia, Lymphoblastic1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
2RecruitingTreatmentLeukemias1
2RecruitingTreatmentUntreated Adult Acute Myeloid Leukemia1
2TerminatedTreatmentHigh-risk Myelodysplastic Syndrome (MDS) / Leukemia Acute Myeloid Leukemia (AML)1
2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2TerminatedTreatmentLeukemias1
2TerminatedTreatmentLeukemias / Lymphoma, Lymphoblastic / Malignant Lymphomas / Precursor-B Acute Lymphoblastic Leukemia1
2Unknown StatusTreatmentLeukemias2
2, 3Active Not RecruitingTreatmentMyeloid Leukemias1
2, 3CompletedTreatmentAdult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
2, 3CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2, 3CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
2, 3Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2, 3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Lymphoma1
2, 3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2, 3RecruitingTreatmentLeukemias1
2, 3RecruitingTreatmentLymphoma, Lymphoblastic1
2, 3Unknown StatusTreatmentDe Novo Akute Myeloid Leukemia (AML) / Refractory Anemia With Excess of Blasts in Transformation / Secondary Acute Myeloid Leukemia (AML)1
2, 3Unknown StatusTreatmentLeukemias1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3Active Not RecruitingTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Acute, secondary Myeloid Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Untreated Adult Acute Myeloid Leukemia1
3Active Not RecruitingTreatmentAcute, secondary Myeloid Leukemia / Childhood Acute Basophilic Leukemia / Childhood Acute Eosinophilic Leukemia / Childhood Acute Erythroleukemia (M6) / Childhood Acute Megakaryocytic Leukemia (M7) / Childhood Acute Minimally Differentiated Myeloid Leukemia (M0) / Childhood Acute Monoblastic Leukemia (M5a) / Childhood Acute Monocytic Leukemia (M5b) / Childhood Acute Myeloblastic Leukemia With Maturation (M2) / Childhood Acute Myeloblastic Leukemia Without Maturation (M1) / Childhood Acute Myelomonocytic Leukemia (M4) / Childhood Myelodysplastic Syndromes / De Novo Myelodysplastic Syndromes / Secondary Myelodysplastic Syndromes / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3Active Not RecruitingTreatmentGranulocytic Sarcoma / Leukaemia cutis / Leukemia Acute Myeloid Leukemia (AML) / Myeloid Neoplasm / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Myeloid Neoplasm1
3Active Not RecruitingTreatmentHigh Risk Acute Myeloid Leukemia1
3Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
3Active Not RecruitingTreatmentLeukemias4
3Active Not RecruitingTreatmentMalignant Lymphomas1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Undifferentiated Leukemia (AUL) / Childhood T Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult T Acute Lymphoblastic Leukemia / Ann Arbor Stage II Adult T-Cell Leukemia/Lymphoma / Ann Arbor Stage II Childhood Lymphoblastic Lymphoma / Ann Arbor Stage II Contiguous Adult Lymphoblastic Lymphoma / Ann Arbor Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Ann Arbor Stage III Adult Lymphoblastic Lymphoma / Ann Arbor Stage III Adult T-Cell Leukemia/Lymphoma / Ann Arbor Stage III Childhood Lymphoblastic Lymphoma / Ann Arbor Stage IV Adult Lymphoblastic Lymphoma / Ann Arbor Stage IV Adult T-Cell Leukemia/Lymphoma / Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma / Childhood T Acute Lymphoblastic Leukemia / Stage II Adult T-Cell Leukemia/Lymphoma / Stage II Childhood Lymphoblastic Lymphoma / Stage II Contiguous Adult Lymphoblastic Lymphoma / Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Adult T-Cell Leukemia/Lymphoma / Stage III Childhood Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / T Acute Lymphoblastic Leukemia / T Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3CompletedTreatmentAdult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Erythroid Leukemia (M6) / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Childhood Acute Basophilic Leukemia / Childhood Acute Eosinophilic Leukemia / Childhood Acute Erythroleukemia (M6) / Childhood Acute Megakaryocytic Leukemia (M7) / Childhood Acute Minimally Differentiated Myeloid Leukemia (M0) / Childhood Acute Monoblastic Leukemia (M5a) / Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5) / Childhood Acute Monocytic Leukemia (M5b) / Childhood Acute Myeloblastic Leukemia With Maturation (M2) / Childhood Acute Myeloblastic Leukemia Without Maturation (M1) / Childhood Acute Myelomonocytic Leukemia (M4) / Childhood Myelodysplastic Syndromes / De Novo Myelodysplastic Syndromes / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3CompletedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Untreated Adult Acute Myeloid Leukemia1
3CompletedTreatmentAcute, secondary Myeloid Leukemia / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Untreated Adult Acute Myeloid Leukemia1
3CompletedTreatmentAdult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Promyelocytic Leukemia (M3) / Childhood Acute Promyelocytic Leukemia (M3) / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3CompletedTreatmentChildhood Acute Erythroleukemia (M6) / Childhood Acute Megakaryocytic Leukemia (M7) / Childhood Acute Monoblastic Leukemia (M5a) / Childhood Acute Monocytic Leukemia (M5b) / Childhood Acute Myeloblastic Leukemia With Maturation (M2) / Childhood Acute Myeloblastic Leukemia Without Maturation (M1) / Childhood Acute Myelomonocytic Leukemia (M4) / Childhood Myelodysplastic Syndromes / Chronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndromes / Refractory Anemia / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation / Refractory Anemia With Ringed Sideroblasts / Secondary Myelodysplastic Syndromes / Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies1
3CompletedTreatmentChildhood Acute Lymphoblastic Leukemia in Remission / Recurrent Childhood Acute Lymphoblastic Leukemia1
3CompletedTreatmentElderly / Leukemia Acute Myeloid Leukemia (AML)1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
3CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)5
3CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
3CompletedTreatmentLeukemia, Myelocytic, Acute1
3CompletedTreatmentLeukemias12
3CompletedTreatmentLeukemias / Malignant Lymphomas2
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes4
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms3
3CompletedTreatmentSarcomas1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / BCR/ABL1 Fusion Protein Negative / Untreated Adult Acute Lymphoblastic Leukemia1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / BCR-ABL1 Fusion Protein Expression / Minimal Residual Disease / Philadelphia Chromosome Positive / T Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Cognitive Side Effects of Cancer Therapy / Neurotoxicity Syndrome / Osteonecrosis / Pain / Ph-Like Acute Lymphoblastic Leukemia / Testicular Leukemia / Therapy-Related Toxicity / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
3RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia1
3RecruitingTreatmentBlasts 5 Percent or More of Bone Marrow Nucleated Cells / Childhood Acute Myeloid Leukemia / Childhood Myelodysplastic Syndrome / Cytopenias / Down Syndrome (DS) / Myeloid Leukemia Associated With Down Syndrome / Myeloproliferative Neoplasms / Trisomy 21 Mosaicism1
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)4
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Leukemias1
3RecruitingTreatmentLeukemias1
3SuspendedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult T Acute Lymphoblastic Leukemia / Ann Arbor Stage II Adult Lymphoblastic Lymphoma / Ann Arbor Stage II Childhood Lymphoblastic Lymphoma / Ann Arbor Stage III Adult Lymphoblastic Lymphoma / Ann Arbor Stage III Childhood Lymphoblastic Lymphoma / Ann Arbor Stage IV Adult Lymphoblastic Lymphoma / Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma / Childhood T Acute Lymphoblastic Leukemia / Stage II Adult Lymphoblastic Lymphoma / Stage II Childhood Lymphoblastic Lymphoma / Stage II Contiguous Adult Lymphoblastic Lymphoma / Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Childhood Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3TerminatedTreatmentMalignant Lymphomas1
3Unknown StatusTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3Unknown StatusTreatmentLeukemias4
3Unknown StatusTreatmentLeukemias / Malignant Lymphomas1
3Unknown StatusTreatmentLeukemias / Mucositis / Oral Complications1
3Unknown StatusTreatmentLeukemias / Neutropenias1
3Unknown StatusTreatmentMalignant Lymphomas2
3Unknown StatusTreatmentSecondary Acute Myeloid Leukemia (Secondary AML, sAML)1
3WithdrawnTreatmentLeukemias1
4Active Not RecruitingPreventionLeukemia Acute Myeloid Leukemia (AML)1
4Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)4
4CompletedTreatmentAdult Acute Lymphocytic Leukemia3
4CompletedTreatmentLymphoma, Lymphoblastic1
4RecruitingTreatmentAcute Lymphobkastic Leukemia1
4RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4Unknown StatusPreventionAcute Promyelocytic Leukemia (APL)1
4Unknown StatusTreatmentAdult Acute Lymphocytic Leukemia1
Not AvailableActive Not RecruitingTreatmentChildhood Acute Lymphoblastic Leukemia1
Not AvailableActive Not RecruitingTreatmentUnspecified Childhood Solid Tumor, Protocol Specific1
Not AvailableCompletedTreatmentAtaxia-Telangiectasia1
Not AvailableCompletedTreatmentB-cell Adult Acute Lymphoblastic Leukemia / B-cell Childhood Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia2
Not AvailableCompletedTreatmentLeukemias3
Not AvailableCompletedTreatmentLymphoma, Lymphoblastic1
Not AvailableCompletedTreatmentT-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
Not AvailableNot Yet RecruitingNot AvailableAcute Myeloid Leukemia With Myelodysplasia-Related Changes / Therapy-Related Acute Myeloid Leukemia1
Not AvailableRecruitingNot AvailableAdult Acute Lymphoblastic Leukemia1
Not AvailableRecruitingOtherLeukemia, Myelocytic, Acute1
Not AvailableRecruitingTreatmentChildhood Acute Lymphoblastic Leukemia1
Not AvailableRecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
Not AvailableUnknown StatusTreatmentLeukemias2
Not AvailableWithdrawnNot AvailableAcute Lymphoblastic Leukaemias (ALL) / Leukemias / Untreated Childhood Acute Lymphoblastic Leukemia1

Pharmacoeconomics

Manufacturers
  • Gilead sciences inc
  • Bedford laboratories div ben venue laboratories inc
  • Sanofi aventis us llc
  • Wyeth ayerst research
  • App pharmaceuticals llc
  • Teva parenteral medicines inc
Packagers
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bigmar Bioren Pharmaceuticals Sa
  • Gilead Sciences Inc.
  • Sicor Pharmaceuticals
  • Specia Alfort
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous20 mg/4mL
Powder, for solutionIntravenous20 mg
InjectionIntravenous5 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous5 mg/1mL
Injection, solutionIntravenous5 mg/1mL
Injection, lipid complexIntravenous2 mg/1mL
SuspensionIntravenous2 mg
Injection, powder, lyophilized, for suspensionIntravenous
Prices
Unit descriptionCostUnit
Daunorubicin 20 mg/4 ml vial163.01USD ml
Cerubidine 20 mg vial50.4USD vial
Daunorubicin 50 mg/10 ml vial42.45USD ml
Daunoxome 2 mg/ml vial13.06USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7850990No2007-01-232027-01-23Us
US8022279No2007-09-142027-09-14Us
US8431806No2005-04-222025-04-22Us
US8092828No2009-04-012029-04-01Us
US8518437No2006-06-072026-06-07Us
US9271931No2007-01-232027-01-23Us
US10028912No2014-09-292034-09-29Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)208-209 °CPhysProp
water solubility39.2 mg/LNot Available
logP1.83SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.627 mg/mLALOGPS
logP1.68ALOGPS
logP1.73ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)9.53ChemAxon
pKa (Strongest Basic)8.94ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area185.84 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity132.89 m3·mol-1ChemAxon
Polarizability52.94 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.6524
Blood Brain Barrier-0.9869
Caco-2 permeable-0.7227
P-glycoprotein substrateSubstrate0.7862
P-glycoprotein inhibitor INon-inhibitor0.636
P-glycoprotein inhibitor IINon-inhibitor0.9136
Renal organic cation transporterNon-inhibitor0.9213
CYP450 2C9 substrateNon-substrate0.7987
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5951
CYP450 1A2 substrateInhibitor0.8777
CYP450 2C9 inhibitorNon-inhibitor0.9448
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9527
CYP450 3A4 inhibitorNon-inhibitor0.9157
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9543
Ames testAMES toxic0.9224
CarcinogenicityNon-carcinogens0.9521
BiodegradationNot ready biodegradable0.9844
Rat acute toxicity3.2275 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9888
hERG inhibition (predictor II)Non-inhibitor0.8916
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as anthracyclines. These are polyketides containing a tetracenequinone ring structure with a sugar attached by glycosidic linkage.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Anthracyclines
Sub Class
Not Available
Direct Parent
Anthracyclines
Alternative Parents
Tetracenequinones / Aminoglycosides / Anthraquinones / Hexoses / O-glycosyl compounds / Tetralins / Anisoles / Aryl ketones / Alkyl aryl ethers / Oxanes
show 12 more
Substituents
Anthracycline / Anthracyclinone-skeleton / Aminoglycoside core / Tetracenequinone / 9,10-anthraquinone / 1,4-anthraquinone / Anthracene / Hexose monosaccharide / Glycosyl compound / O-glycosyl compound
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinone, aminoglycoside antibiotic, anthracycline (CHEBI:41977) / Anthracyclinones (C01907) / Anthracyclinones (LMPK13050002)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [PubMed:6380596]
  2. Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [PubMed:1963303]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
References
  1. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [PubMed:6380596]
  2. Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [PubMed:1963303]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein kinase c binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Gene Name
TOP2B
Uniprot ID
Q02880
Uniprot Name
DNA topoisomerase 2-beta
Molecular Weight
183265.825 Da
References
  1. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [PubMed:6380596]
  2. Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [PubMed:1963303]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Baumhakel M, Kasel D, Rao-Schymanski RA, Bocker R, Beckurts KT, Zaigler M, Barthold D, Fuhr U: Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int J Clin Pharmacol Ther. 2001 Dec;39(12):517-28. [PubMed:11770832]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Wang T, Chen FY, Han JY, Shao NX, Ou-Yuang RR: [Study of CYP3A5 in drug resistance mechanisms in acute leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2003 Jun;24(6):286-9. [PubMed:12859862]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Yee SB, Pritsos CA: Comparison of oxygen radical generation from the reductive activation of doxorubicin, streptonigrin, and menadione by xanthine oxidase and xanthine dehydrogenase. Arch Biochem Biophys. 1997 Nov 15;347(2):235-41. [PubMed:9367530]
  2. Yee SB, Pritsos CA: Reductive activation of doxorubicin by xanthine dehydrogenase from EMT6 mouse mammary carcinoma tumors. Chem Biol Interact. 1997 May 2;104(2-3):87-101. [PubMed:9212777]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name
POR
Uniprot ID
P16435
Uniprot Name
NADPH--cytochrome P450 reductase
Molecular Weight
76689.12 Da
References
  1. Bachur NR, Gordon SL, Gee MV, Kon H: NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals. Proc Natl Acad Sci U S A. 1979 Feb;76(2):954-7. [PubMed:34156]
  2. Di Re J, Lee C, Riddick DS: Lack of mechanism-based inactivation of rat hepatic microsomal cytochromes P450 by doxorubicin. Can J Physiol Pharmacol. 1999 Aug;77(8):589-97. [PubMed:10543722]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Zhou G, Kuo MT: Wild-type p53-mediated induction of rat mdr1b expression by the anticancer drug daunorubicin. J Biol Chem. 1998 Jun 19;273(25):15387-94. [PubMed:9624121]
  2. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. [PubMed:11405287]
  3. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674]
  4. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. [PubMed:12134945]
  5. Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. [PubMed:10746169]
  6. Tang F, Ouyang H, Yang JZ, Borchardt RT: Bidirectional transport of rhodamine 123 and Hoechst 33342, fluorescence probes of the binding sites on P-glycoprotein, across MDCK-MDR1 cell monolayers. J Pharm Sci. 2004 May;93(5):1185-94. [PubMed:15067695]
  7. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [PubMed:11785684]
  8. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. [PubMed:10617675]
  9. Takara K, Sakaeda T, Kakumoto M, Tanigawara Y, Kobayashi H, Okumura K, Ohnishi N, Yokoyama T: Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport. Oncol Res. 2009;17(11-12):527-33. [PubMed:19806783]
  10. Borska S, Sopel M, Chmielewska M, Zabel M, Dziegiel P: Quercetin as a potential modulator of P-glycoprotein expression and function in cells of human pancreatic carcinoma line resistant to daunorubicin. Molecules. 2010 Feb 9;15(2):857-70. doi: 10.3390/molecules15020857. [PubMed:20335952]
  11. Perez-Victoria JM, Chiquero MJ, Conseil G, Dayan G, Di Pietro A, Barron D, Castanys S, Gamarro F: Correlation between the affinity of flavonoids binding to the cytosolic site of Leishmania tropica multidrug transporter and their efficiency to revert parasite resistance to daunomycin. Biochemistry. 1999 Feb 9;38(6):1736-43. [PubMed:10026252]
  12. Pallis M, Turzanski J, Harrison G, Wheatley K, Langabeer S, Burnett AK, Russell NH: Use of standardized flow cytometric determinants of multidrug resistance to analyse response to remission induction chemotherapy in patients with acute myeloblastic leukaemia. Br J Haematol. 1999 Feb;104(2):307-12. [PubMed:10050713]
  13. Chiodini B, Bassan R, Barbui T: Cellular uptake and antiproliferative effects of therapeutic concentrations of idarubicin or daunorubicin and their alcohol metabolites, with or without cyclosporin A, in MDR1+ human leukemic cells. Leuk Lymphoma. 1999 May;33(5-6):485-97. [PubMed:10342576]
  14. Romsicki Y, Sharom FJ: The membrane lipid environment modulates drug interactions with the P-glycoprotein multidrug transporter. Biochemistry. 1999 May 25;38(21):6887-96. [PubMed:10346910]
  15. Hiessbock R, Wolf C, Richter E, Hitzler M, Chiba P, Kratzel M, Ecker G: Synthesis and in vitro multidrug resistance modulating activity of a series of dihydrobenzopyrans and tetrahydroquinolines. J Med Chem. 1999 Jun 3;42(11):1921-6. [PubMed:10354400]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Loe DW, Almquist KC, Cole SP, Deeley RG: ATP-dependent 17 beta-estradiol 17-(beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. J Biol Chem. 1996 Apr 19;271(16):9683-9. [PubMed:8621644]
  2. Heijn M, Hooijberg JH, Scheffer GL, Szabo G, Westerhoff HV, Lankelma J: Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport. Biochim Biophys Acta. 1997 May 22;1326(1):12-22. [PubMed:9188796]
  3. Priebe W, Krawczyk M, Kuo MT, Yamane Y, Savaraj N, Ishikawa T: Doxorubicin- and daunorubicin-glutathione conjugates, but not unconjugated drugs, competitively inhibit leukotriene C4 transport mediated by MRP/GS-X pump. Biochem Biophys Res Commun. 1998 Jun 29;247(3):859-63. [PubMed:9647783]
  4. Godinot N, Iversen PW, Tabas L, Xia X, Williams DC, Dantzig AH, Perry WL 3rd: Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey. Mol Cancer Ther. 2003 Mar;2(3):307-16. [PubMed:12657726]
  5. Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG: Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos. 2003 Aug;31(8):1016-26. [PubMed:12867490]
  6. Versantvoort CH, Broxterman HJ, Lankelma J, Feller N, Pinedo HM: Competitive inhibition by genistein and ATP dependence of daunorubicin transport in intact MRP overexpressing human small cell lung cancer cells. Biochem Pharmacol. 1994 Sep 15;48(6):1129-36. [PubMed:7945406]
  7. Yazaki K, Yamanaka N, Masuno T, Konagai S, Shitan N, Kaneko S, Ueda K, Sato F: Heterologous expression of a mammalian ABC transporter in plant and its application to phytoremediation. Plant Mol Biol. 2006 Jun;61(3):491-503. [PubMed:16830181]
  8. Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SP, Deeley RG: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53. [PubMed:9281595]
  9. Nabekura T, Yamaki T, Hiroi T, Ueno K, Kitagawa S: Inhibition of anticancer drug efflux transporter P-glycoprotein by rosemary phytochemicals. Pharmacol Res. 2010 Mar;61(3):259-63. doi: 10.1016/j.phrs.2009.11.010. Epub 2009 Nov 26. [PubMed:19944162]
  10. Renes J, de Vries EG, Nienhuis EF, Jansen PL, Muller M: ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1. Br J Pharmacol. 1999 Feb;126(3):681-8. [PubMed:10188979]
  11. Hooijberg JH, Pinedo HM, Vrasdonk C, Priebe W, Lankelma J, Broxterman HJ: The effect of glutathione on the ATPase activity of MRP1 in its natural membranes. FEBS Lett. 2000 Mar 3;469(1):47-51. [PubMed:10708754]
  12. Marbeuf-Gueye C, Salerno M, Quidu P, Garnier-Suillerot A: Inhibition of the P-glycoprotein- and multidrug resistance protein-mediated efflux of anthracyclines and calceinacetoxymethyl ester by PAK-104P. Eur J Pharmacol. 2000 Mar 17;391(3):207-16. [PubMed:10729360]
  13. Evers R, Kool M, Smith AJ, van Deemter L, de Haas M, Borst P: Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1 Pgp-, MRP1- and MRP2-mediated transport. Br J Cancer. 2000 Aug;83(3):366-74. [PubMed:10917553]
  14. Evers R, de Haas M, Sparidans R, Beijnen J, Wielinga PR, Lankelma J, Borst P: Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83. [PubMed:10917554]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
Multidrug resistance-associated protein 7
Molecular Weight
161627.375 Da
References
  1. Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. doi: 10.1158/0008-5472.CAN-08-1420. [PubMed:19118001]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. [PubMed:12134946]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4...
Gene Name
ABCC6
Uniprot ID
O95255
Uniprot Name
Multidrug resistance-associated protein 6
Molecular Weight
164904.81 Da
References
  1. Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. [PubMed:12414644]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [PubMed:12739759]
  2. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. [PubMed:10617675]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, van Veen HW: Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51. Epub 2003 Mar 28. [PubMed:12668685]
  2. Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B: Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7. [PubMed:11437380]
  3. Nakanishi T, Doyle LA, Hassel B, Wei Y, Bauer KS, Wu S, Pumplin DW, Fang HB, Ross DD: Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis. Mol Pharmacol. 2003 Dec;64(6):1452-62. [PubMed:14645676]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:29