DAUNORUBICIN CITRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H29NO10.C6H8O7
Molecular Weight	719.6434
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC(O)(CC(O)=O)C(O)=O.[H][C@@]1(C[C@@](O)(CC2=C(O)C3=C(C(=O)C4=C(C=CC=C4OC)C3=O)C(O)=C12)C(C)=O)O[C@H]5C[C@H](N)[C@H](O)[C@H](C)O5

InChI

InChIKey=VNTHYLVDGVBPOU-QQYBVWGSSA-N

InChI=1S/C27H29NO10.C6H8O7/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;7-3(8)1-6(13,5(11)12)2-4(9)10/h4-6,10,14,16-17,22,30,32,34-35H,7-9,28H2,1-3H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t10-,14-,16-,17-,22+,27-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C6H8O7
Molecular Weight	192.1235
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C27H29NO10
Molecular Weight	527.5199
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugs.com/dosage/daunorubicin.html
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22260166 | https://www.ncbi.nlm.nih.gov/pubmed/7932544 | https://www.ncbi.nlm.nih.gov/pubmed/13146115 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050467s070lbl.pdf

Daunorubicin, also known as daunomycin, is a chemotherapy medication used to treat cancer. Specifically, it is used for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and Kaposi's sarcoma. Similar to doxorubicin, daunorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of the enzyme topoisomerase II, which relaxes supercoils in DNA for transcription. Daunorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. On binding to DNA, daunomycin intercalates, with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C base pairs flanked on the 5' side by an A/T base pair. Daunorubicin should only be administered in a rapid intravenous infusion. It should not be administered intramuscularly or subcutaneously, since it may cause extensive tissue necrosis. It should also never be administered intrathecally (into the spinal canal), as this will cause extensive damage to the nervous system and may lead to death.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
DNA topoisomerase II alpha 37 Target ID: CHEMBL1806 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22260166	Inhibitor 8297
DNA topoisomerase I 59 Target ID: CHEMBL1781 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7932544	Inhibitor 8297
Multidrug resistance-associated protein 1 15 Target ID: CHEMBL3004 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9647783	Inhibitor 8297	70.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Acute lymphoblastic leukemia 27 Sources: https://www.drugs.com/dosage/daunorubicin.html	Primary	Approved 8429	CERUBIDINE Approved Use Daunorubicin hydrochloride injection 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. Launch Date 1979
Acute myeloblastic leukemia 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050467s070lbl.pdf	Primary	Approved 8429	CERUBIDINE Approved Use Daunorubicin hydrochloride injection 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. Launch Date 1979
Neuroblastoma 25 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050467s070lbl.pdf	Primary	Approved 8429	CERUBIDINE Approved Use Daunorubicin hydrochloride injection 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. Launch Date 1979

C_max

Value	Dose	Co-administered	Analyte	Population
26 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf	44 mg/m² 1 times / 2 days multiple, intravenous dose: 44 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: Cytarabine	Cytarabine	DAUNORUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
637 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf	44 mg/m² 1 times / 2 days multiple, intravenous dose: 44 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: Cytarabine	Cytarabine	DAUNORUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
31.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf	44 mg/m² 1 times / 2 days multiple, intravenous dose: 44 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: Cytarabine	Cytarabine	DAUNORUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
3% REVIEW https://clincancerres.aacrjournals.org/content/clincanres/early/2017/06/26/1078-0432.CCR-16-3083.full.pdf			DAUNORUBICIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
190 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 190 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 190 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/16880787 Page: p.573, 575	unhealthy, 10 n = 6 Health Status: unhealthy Condition: Cancer Age Group: 10 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/16880787 Page: p.573, 575	DLT: Neutropenia, Leucopenia... Dose limiting toxicities: Neutropenia (grade 4, 100%) Leucopenia (grade 4, 100%) Thrombocytopenia (grade 4, 16.7%) Anemia (grade 4, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/16880787 Page: p.573, 575
155 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 155 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 155 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/16880787 Page: p.573, 575	unhealthy, 10 n = 6 Health Status: unhealthy Condition: Cancer Age Group: 10 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/16880787 Page: p.573, 575	DLT: Neutropenia, Leucopenia... Disc. AE: Cardiac failure... Dose limiting toxicities: Neutropenia (grade 4, 100%) Leucopenia (grade 4, 50%) AEs leading to discontinuation/dose reduction: Cardiac failure (grade 5, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/16880787 Page: p.573, 575
50 mg/m2 1 times / 4 weeks multiple, intravenous Recommended Dose: 50 mg/m2, 1 times / 4 weeks Route: intravenous Route: multiple Dose: 50 mg/m2, 1 times / 4 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.11	unhealthy, 27-87 n = 239 Health Status: unhealthy Condition: Ovarian Cancer Age Group: 27-87 Sex: M+F Population Size: 239 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.11	Disc. AE: Skin toxicity... AEs leading to discontinuation/dose reduction: Skin toxicity (4.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.11
20 mg/m2 1 times / 2 weeks multiple, intravenous Recommended Dose: 20 mg/m2, 1 times / 2 weeks Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / 2 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.11	unhealthy, 38.7 n = 705 Health Status: unhealthy Condition: AIDS-related Kaposi’s sarcoma Age Group: 38.7 Sex: M+F Population Size: 705 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.11	Disc. AE: Skin eruption... AEs leading to discontinuation/dose reduction: Skin eruption (0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.11
80 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 80 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 80 mg/m2, 1 times / 3 weeks Co-administed with:: vincristine, i.v(1.4 mg/m2, day 1) dexamethasone, p.o(40 mg/day, days 1–4 and 9–12) Sources: https://pubmed.ncbi.nlm.nih.gov/14597873 Page: p.795	unhealthy, 60 n = 3 Health Status: unhealthy Condition: Multiple myeloma Age Group: 60 Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/14597873 Page: p.795	Sources: https://pubmed.ncbi.nlm.nih.gov/14597873 Page: p.795
100 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 100 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / 3 weeks Co-administed with:: vincristine, i.v(1.4 mg/m2, day 1) dexamethasone, p.o(40 mg/day, days 1–4 and 9–12) Sources: https://pubmed.ncbi.nlm.nih.gov/14597873 Page: p.795	unhealthy, 60 n = 3 Health Status: unhealthy Condition: Multiple myeloma Age Group: 60 Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/14597873 Page: p.795	DLT: Acute diverticular perforation... Dose limiting toxicities: Acute diverticular perforation Sources: https://pubmed.ncbi.nlm.nih.gov/14597873 Page: p.795
100 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 100 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / 3 weeks Co-administed with:: dexamethasone, p.o(40 mg/day, days 1–4) Sources: https://pubmed.ncbi.nlm.nih.gov/12173332 Page: p.2648	unhealthy, 63 n = 38 Health Status: unhealthy Condition: Multiple myeloma Age Group: 63 Sex: M+F Population Size: 38 Sources: https://pubmed.ncbi.nlm.nih.gov/12173332 Page: p.2648	Disc. AE: Ejection fraction decreased, Prolonged neutropenia... Other AEs: Granulocytopenia, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Ejection fraction decreased (5.3%) Prolonged neutropenia (2.6%) Other AEs: Granulocytopenia (grade 4, 21%) Thrombocytopenia (grade 4, 8%) Febrile neutropenia (grade 4, 11%) Sources: https://pubmed.ncbi.nlm.nih.gov/12173332 Page: p.2648
50 mg/m2 1 times / 4 weeks multiple, intravenous Recommended Dose: 50 mg/m2, 1 times / 4 weeks Route: intravenous Route: multiple Dose: 50 mg/m2, 1 times / 4 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Ovarian Cancer Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.1	Disc. AE: Infusion related reaction, Myelosuppression... AEs leading to discontinuation/dose reduction: Infusion related reaction (acute) Myelosuppression (severe) Cardiotoxicity Congestive heart failure Hepatic impairment Reaction anaphylactic anaphylactoid (grade 3-5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050718s033lbl.pdf Page: p.1

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP2 383	BCRP 561	CYP3A5 76

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11770832/	yes [IC50 203 uM]
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12134946/	yes [Ki 49.4 uM]
CYP3A5 130	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/12859862/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11437380/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:41977	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:41977
ChemicalBook	CB0338996	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0338996
ZINC	ZINC000003917708	http://zinc15.docking.org/substances/ZINC000003917708
eMolecules	30152546	https://www.emolecules.com/cgi-bin/more?vid=30152546

PubMed

Title	Date	PubMed
[Possibility for the prevention of cardio toxic effect of Cerubidin].	1975 Aug 24	1057758
Endomyocardial fibrosis associated with daunorubicin therapy.	1976 Aug	1067858
Tumorigenicity in vivo and induction of malignant transformation and mutagenesis in cell cultures by adriamycin and daunomycin.	1976 Jun	1268859
Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members.	1999 Oct 15	10510318
Anthracyclines trigger apoptosis of both G0-G1 and cycling peripheral blood lymphocytes and induce massive deletion of mature T and B cells.	2000 Apr 1	10766178
Chest and back pain associated with a six-hour infusion of liposomal daunorubicin.	2000 Jun	10860143
[Severe hemolysis and SIADH-like symptoms induced by vincristine in an ALL patient with liver cirrhosis].	2000 Nov	11193445
Prevention by dexrazoxane of down-regulation of ryanodine receptor gene expression in anthracycline cardiomyopathy in the rat.	2000 Sep	10960060
Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport.	2001 Feb	11231118
Down-regulation of catalase gene expression in the doxorubicin-resistant AML subline AML-2/DX100.	2001 Feb 16	11178967
High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia.	2001 Jul 1	11443603
[Characteristics of mutants of Streptomyces peucetius subsp. caesius ATCC 27952 resistant to anthracycline antibiotics].	2001 Jul-Aug	11692678
Liposomal encapsulated anthracyclines: new therapeutic horizons.	2001 Mar	11177748
Benign thymic hyperplasia after chemotherapy for acute myeloid leukemia.	2001 Oct	11860447
Effect of aging on cardiac contractility in a rat model of chronic daunorubicin cardiotoxicity.	2002	12271153
Effects of dietary lipids on daunomycin-induced nephropathy in mice: comparison between cod liver oil and soybean oil.	2002 Apr	12030316
Comparison of idarubicin and daunorubicin regarding intracellular uptake, induction of apoptosis, and resistance.	2002 Apr 25	11867198
Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia.	2002 Aug	12224004
Reversal of multidrug resistance-associated protein-mediated daunorubicin resistance by camptothecin.	2002 Aug	12115804
Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis.	2002 Dec	12370496
Role of exogenous melatonin in reducing the cardiotoxic effect of daunorubicin and doxorubicin in the rat.	2002 Feb	11926284
A novel, extraneuronal role for cyclin-dependent protein kinase 5 (CDK5): modulation of cAMP-induced apoptosis in rat leukemia cells.	2002 Jun 7	11909854
Resistance of bcr-abl-positive acute lymphoblastic leukemia to daunorubicin is not mediated by mdr1 gene expression.	2002 Nov	12410571
Nucleotide triphosphatase/helicase of hepatitis C virus as a target for antiviral therapy.	2002 Sep	12206878
High-dose daunorubicin as liposomal compound (Daunoxome) in elderly patients with acute lymphoblastic leukemia.	2003	12692520
Impact of neutropenia on delivering planned adjuvant chemotherapy: UK audit of primary breast cancer patients.	2003 Dec 1	14647139
Vincristine neurotoxicity in the presence of hereditary neuropathy.	2003 Jan	12426685
Cytotoxic drugs enhance the ex vivo sensitivity of malignant cells from a subset of acute myeloid leukaemia patients to apoptosis induction by tumour necrosis factor receptor-related apoptosis-inducing ligand.	2003 Jun	12780785
Daunorubicin-induced variations in gene transcription: commitment to proliferation arrest, senescence and apoptosis.	2003 Jun 15	12656675
The dose related effect of steroids on blast reduction rate and event free survival in children with acute lymphoblastic leukemia.	2003 Mar	12688320
[Successful treatment after acute promyelocytic leukemia (APL) syndrome of relapsed API with arsenic trioxide].	2003 Mar	12669407
Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey.	2003 Mar	12657726
Cardiac troponin T as an indicator of reduced left ventricular contractility in experimental anthracycline-induced cardiomyopathy.	2003 Nov	14618274
Liposomal daunorubicin (DaunoXome) in multiple myeloma: a modified VAD regimen using short-term infusion.	2003 Nov	14597873
Population pharmacokinetics of liposomal daunorubicin in children.	2003 Oct	12968981
Human intestinal absorption of imidacloprid with Caco-2 cells as enterocyte model.	2004 Jan 1	14728974

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Acute Nonlymphocytic Leukemia: Under 60 years of age: 45 mg/m2 IV over 2 to 5 minutes once a day on days 1, 2, and 3 for the first course and on days 1 and 2 for subsequent courses) with cytosine arabinoside (ara-C) intravenously once a day (usually for 7 days for the first course and 5 days for subsequent courses) as remission induction therapy.

Route of Administration: Intravenous

In Vitro Use Guide

In order to determine the viability of HL-60, K562, THP-1, and HEK293T cells, they were trypsinized, counted, and seeded into 96-well plates and were treated with serial dilutions (0.0001, 0.001, 0.01, 0.1, 1 mkM) of DNR (Daunorubicin). Cell viability was determined 48 h after DNR treatment using the luminescent cell viability assay (Promega) through luminescence testing by BMG NOVOstar machine.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:56:03 GMT 2023` Edited by `admin` on `Fri Dec 15 15:56:03 GMT 2023`
Record UNII	5L84T2Z6NP
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DAUNORUBICIN CITRATE

Common Name

English

Daunorubicin Citrate [WHO-DD]

Common Name

English

DAUNORUBICIN LIPOSOMAL

Brand Name

English

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)-, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (1:1)

Common Name

English

DAUNORUBICIN CITRATE [ORANGE BOOK]

Common Name

English

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)-, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (1:1) (SALT)

Common Name

English

DAUNOXOME

Brand Name

English

DAUNORUBICIN CITRATE LIPOSOME

Common Name

English

DAUNORUBICIN CITRATE LIPOSOME [VANDF]

Common Name

English

DAUNORUBICIN CITRATE [MART.]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

73693