Daunorubicin

Identification

Summary

Daunorubicin is an anthracycline aminoglycoside used to induce remission of nonlymphocytic leukemia and acute lymphocytic leukemia.

Brand Names

Cerubidine, Vyxeos

Generic Name

Daunorubicin

DrugBank Accession Number

DB00694

Background

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

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 527.5199
Monoisotopic: 527.179146153
Chemical Formula: C₂₇H₂₉NO₁₀

Synonyms

(+)-Daunomycin
(8S-cis)-8-acetyl-10-((3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyrannosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-napthacenedione
Acetyladriamycin
Daunomycin
Daunorubicin
Daunorubicin liposomal
Daunorubicina
Daunorubicine
Daunorubicinum
Leukaemomycin C
Rubidomycin

External IDs

DNR
FI 6339
NSC 82151
RCRA Waste No. U059
RP 13057
RP-13057

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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.

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

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Acute lymphoblastic leukaemias (all)		••••••••••••			•••••••••
Used in combination to treat	Acute myeloid leukemia with myelodysplasia-related changes	Combination Product in combination with: Cytarabine (DB00987)	••••••••••••	••••••••••• •••••• •••••••••	••••• •••••••••
Treatment of	Ewing's tumor		••••••••••••			•••••••••
Treatment of	Lymphoma, diffuse		••••••••••••			•••••••••
Treatment of	Myeloblastic leukemia		••••••••••••			•••••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

Daunorubicin is an anthracycline antibiotic and antineoplastic agent.⁵ 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.

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.

Target	Actions	Organism
ADNA	intercalation	Humans
ADNA topoisomerase 2-alpha	inhibitor	Humans
ADNA topoisomerase 2-beta	inhibitor	Humans

Absorption

Daunorubicin was found to have a tmax of 2 h and a cmax of 24.8 μg/mL after a 90 min infusion of the liposomal formulation at a dose of 44 mg/m². ³

Volume of distribution

Daunorubicin has a steady-state volume of distribution of 1.91 L/m² reported with the liposomal formulation.¹ The average volume of distribution reported for the liposomal formulation is 6.6 L. ⁵

Protein binding

Not Available

Metabolism

Hover over products below to view reaction partners

Daunorubicin
- Daunorubicinol
  - Deoxydaunorubicinol aglycone
  - Daunorubicinol aglycone
- Deoxydaunorubicin aglycone
  - Deoxydaunorubicinol aglycone
    - Demethyl deoxydaunorubicinol aglycone
      - Demethyl deoxydaunorubicinol aglycone-4-O-β-glucuronide
      - Demethyl deoxydaunorubicinol aglycone-4-O-sulfate
    - Deoxydaunorubicinol aglycone-13-O-β-glucuronide

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.⁷ In the liposomal formulation, only 9% of active molecules are excreted in the urine.⁵

Half-life

Daunorubicin has been determined to have a terminal half-life of 18.5 h (+/- 4.9).¹ 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.^3,5

Clearance

Daunorubicin has a clearance of 68.4 mL/h/m² determined using the liposomal formulation.³

Adverse Effects

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Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Cytochrome P450 1B1	---	(G;G) / (C;G)	G allele	ADR Directly Studied	The 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 allele	ADR Directly Studied	The 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 allele	ADR Directly Studied	The 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 allele	ADR Directly Studied	The 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>T	ADR Directly Studied	Pediatric 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 > A	ADR Directly Studied	Pediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with daunorubicin.	Details
UDP-glucuronosyltransferase 1-6	UGT1A6*4	(T;T) / (G;T)	G > T	ADR Directly Studied	Pediatric patients who carry this genotype may be at a higher risk of experiencing anthracycline-induced cardiotoxicity when treated with daunorubicin.	Details

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abatacept	The risk or severity of adverse effects can be increased when Daunorubicin is combined with Abatacept.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Daunorubicin.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Daunorubicin.
Acalabrutinib	The serum concentration of Acalabrutinib can be increased when it is combined with Daunorubicin.
Acenocoumarol	The serum concentration of Acenocoumarol can be increased when it is combined with Daunorubicin.

Food Interactions

No interactions found.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Daunorubicin citrate	5L84T2Z6NP	371770-68-2	VNTHYLVDGVBPOU-QQYBVWGSSA-N
Daunorubicin hydrochloride	UD984I04LZ	23541-50-6	GUGHGUXZJWAIAS-UHFFFAOYSA-N

International/Other Brands

Cerubidin (Sanofi-Aventis) / Cérubidine (Sanofi-Aventis) / Daunoblastin (Pfizer) / Daunoblastina (Pfizer) / Daunorrubicina (GP-Pharm) / Maxidauno (Varifarma)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cerubidine	Powder, for solution	20 mg / vial	Intravenous	Searchlight Pharma Inc	1971-12-31	Not applicable
Daunorubicin Hydrochloride	Injection, powder, for solution	20 mg/1	Intravenous	sanofi-aventis U.S. LLC	2014-06-23	2014-11-11
Daunorubicin Hydrochloride	Injection	5 mg/1mL	Intravenous	Hikma Pharmaceuticals USA Inc.	2018-01-02	Not applicable
Daunorubicin Hydrochloride	Injection	5 mg/1mL	Intravenous	Hikma Pharmaceuticals USA Inc.	2018-01-02	Not applicable
Daunorubicin Hydrochloride for Injection	Powder, for solution	20 mg / vial	Intravenous	TEVA Canada Limited	1998-03-04	2018-04-30

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cerubidine	Injection, powder, for solution	20 mg/4mL	Intravenous	Bedford Pharmaceuticals	1998-06-01	2013-09-30
Daunorubicin Hydrochloride	Injection, solution	5 mg/1mL	Intravenous	Hisun Pharmaceuticals Usa, Inc.	2020-01-20	Not applicable
Daunorubicin Hydrochloride	Injection, solution	5 mg/1mL	Intravenous	Bedford Pharmaceuticals	1998-07-13	2012-10-31
Daunorubicin Hydrochloride	Injection, solution	5 mg/1mL	Intravenous	Teva Parenteral Medicines, Inc.	2004-04-01	2016-06-30
Daunorubicin Hydrochloride	Injection, solution	5 mg/1mL	Intravenous	Hisun Pharmaceuticals Usa, Inc.	2020-01-20	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Vyxeos	Daunorubicin (44 mg) + Cytarabine (100 mg)	Powder	Intravenous	Jazz Pharmaceuticals Ireland Limited	2021-07-06	Not applicable
Vyxeos	Daunorubicin (44 mg/20mL) + Cytarabine (100 mg/20mL)	Injection, powder, lyophilized, for suspension	Intravenous	Jazz Pharmaceuticals, Inc.	2017-08-03	Not applicable
Vyxeos Liposomal	Daunorubicin hydrochloride (2.2 mg/ml) + Cytarabine (5 mg/ml)	Injection, powder, for solution	Intravenous	Jazz Pharmaceuticals Ireland Limited	2020-12-16	Not applicable
VYXEOS LIPOSOMAL	Daunorubicin (2.2 mg/ML) + Cytarabine (5 MG/ML)	Powder	Intravenous; Parenteral	Jazz Pharmaceuticals Ireland Limited	2019-01-29	Not applicable
Vyxeos Liposomal	Daunorubicin hydrochloride (2.2 mg/ml) + Cytarabine (5 mg/ml)	Injection, powder, for solution	Intravenous	Jazz Pharmaceuticals Ireland Limited	2020-12-16	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Daunorubicin Hydrochloride	Daunorubicin hydrochloride (20 mg/1)	Injection, powder, for solution	Intravenous	sanofi-aventis U.S. LLC	2014-06-23	2014-11-11

Chemical Identifiers

UNII: ZS7284E0ZP
CAS number: 20830-81-3
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

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

Balis FM, Holcenberg JS, Bleyer WA: Clinical pharmacokinetics of commonly used anticancer drugs. Clin Pharmacokinet. 1983 May-Jun;8(3):202-32. doi: 10.2165/00003088-198308030-00002. [Article]
Cafaro A, Giannini MB, Silimbani P, Cangini D, Masini C, Ghelli Luserna Di Rora A, Simonetti G, Martinelli G, Cerchione C: CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia. Minerva Med. 2020 Oct;111(5):455-466. doi: 10.23736/S0026-4806.20.07017-2. Epub 2020 Sep 21. [Article]
Mayer LD, Tardi P, Louie AC: CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. Int J Nanomedicine. 2019 May 23;14:3819-3830. doi: 10.2147/IJN.S139450. eCollection 2019. [Article]
Saleem T, Kasi A: Daunorubicin . [Article]
FDA Approved Drug Products: VYXEOS (daunorubicin and cytarabine) liposome for injection, for intravenous use [Link]
Health Canada Approved Drug Products: daunorubicin solution for injection [Link]
FDA Approved Drug Products: Daunorubicin hydrochloride injection [Link]

External Links

Human Metabolome Database: HMDB0014832
KEGG Drug: D07776
KEGG Compound: C01907
PubChem Compound: 30323
PubChem Substance: 46508433
ChemSpider: 28163
BindingDB: 50368352
RxNav: 3109
ChEBI: 41977
ChEMBL: CHEMBL178
ZINC: ZINC000003917708
Therapeutic Targets Database: DNC000517
PharmGKB: PA449212
PDBe Ligand: DM1
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Daunorubicin

PDB Entries

110d / 152d / 1d10 / 1d11 / 1d33 / 1da0 / 1jo2 / 1o0k / 1vth / 1vti …

show 9 more

MSDS

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Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Prevention	Acute Myeloid Leukemia	1
4	Completed	Treatment	Acute Lymphobkastic Leukemia	1
4	Completed	Treatment	Acute Lymphoblastic Leukaemias (ALL)	5
4	Completed	Treatment	Leukemia, Lymphocytic, Acute, Adult	4
4	Completed	Treatment	Leukemias	1

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

Form	Route	Strength
Injection, powder, for solution	Intravenous	20 mg/4mL
Powder, for solution	Intravenous	20 mg / vial
Solution	Intravenous	21.40 mg
Injection, solution	Parenteral	20 mg
Injection, powder, for solution	Parenteral	20 MG/10ML
Injection, powder, for solution	Intravenous
Injection	Intravenous
Injection, powder, for solution	Intravenous	20 mg
Injection, powder, for solution
Injection	Intravenous	5 mg/1mL
Injection, powder, for solution	Intravenous	20 mg/1
Injection, powder, lyophilized, for solution	Intravenous	5 mg/1mL
Injection, solution	Intravenous	5 mg/1mL
Solution	Intravenous	20 mg / 4 mL
Solution	Intravenous	50 mg / 10 mL
Injection, powder, lyophilized, for solution	Intravenous	20 mg
Injection, lipid complex	Intravenous	2 mg/1mL
Suspension	Intravenous	2 mg / mL
Solution	Intravenous	21.400 mg
Injection, powder, lyophilized, for suspension	Intravenous
Powder	Intravenous
Injection, powder, for solution	Intravenous
Powder	Intravenous; Parenteral
Injection, suspension		20.000 mg

Prices

Unit description	Cost	Unit
Daunorubicin 20 mg/4 ml vial	163.01USD	ml
Cerubidine 20 mg vial	50.4USD	vial
Daunorubicin 50 mg/10 ml vial	42.45USD	ml
Daunoxome 2 mg/ml vial	13.06USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US7850990	No	2010-12-14	2027-01-23
US8022279	No	2011-09-20	2027-09-14
US8431806	No	2013-04-30	2025-04-22
US8092828	No	2012-01-10	2029-04-01
US8518437	No	2013-08-27	2026-06-07
US9271931	No	2016-03-01	2027-01-23
US10028912	No	2018-07-24	2034-09-29
US10166184	No	2019-01-01	2032-10-15
US10835492	No	2020-11-17	2032-10-15

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	208-209 °C	PhysProp
boiling point (°C)	190 °C	PubChem
water solubility	30000 mg/L at 25 °C	PubChem
logP	1.83	SANGSTER (1993)
pKa	7.85	PubChem

Predicted Properties

Property	Value	Source
Water Solubility	0.627 mg/mL	ALOGPS
logP	1.68	ALOGPS
logP	1.36	Chemaxon
logS	-2.9	ALOGPS
pKa (Strongest Acidic)	8.01	Chemaxon
pKa (Strongest Basic)	10.03	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	11	Chemaxon
Hydrogen Donor Count	5	Chemaxon
Polar Surface Area	185.84 Å²	Chemaxon
Rotatable Bond Count	4	Chemaxon
Refractivity	132.89 m³·mol^-1	Chemaxon
Polarizability	53.7 Å³	Chemaxon
Number of Rings	5	Chemaxon
Bioavailability	0	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	-	0.6524
Blood Brain Barrier	-	0.9869
Caco-2 permeable	-	0.7227
P-glycoprotein substrate	Substrate	0.7862
P-glycoprotein inhibitor I	Non-inhibitor	0.636
P-glycoprotein inhibitor II	Non-inhibitor	0.9136
Renal organic cation transporter	Non-inhibitor	0.9213
CYP450 2C9 substrate	Non-substrate	0.7987
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Substrate	0.5951
CYP450 1A2 substrate	Inhibitor	0.8777
CYP450 2C9 inhibitor	Non-inhibitor	0.9448
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9527
CYP450 3A4 inhibitor	Non-inhibitor	0.9157
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9543
Ames test	AMES toxic	0.9224
Carcinogenicity	Non-carcinogens	0.9521
Biodegradation	Not ready biodegradable	0.9844
Rat acute toxicity	3.2275 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9888
hERG inhibition (predictor II)	Non-inhibitor	0.8916

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0006-9200300000-b86566e84001e30da377
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03gi-0108090000-9b5e11033a781f155965
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-00os-0009020000-9b31c42030739d82aeb3
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03ec-0209760000-26636262d4edaf9ceb53
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-002b-0109010000-a72365a9821b104a18cb
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-01ta-1724950000-4efae1952fe012fb5d6f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-00l2-0319420000-c8216989f7cb67458285

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	230.9855766	predicted	DarkChem Lite v0.1.0
[M-H]-	231.5901766	predicted	DarkChem Lite v0.1.0
[M-H]-	213.96645	predicted	DeepCCS 1.0 (2019)
[M+H]+	231.3484766	predicted	DarkChem Lite v0.1.0
[M+H]+	232.6141766	predicted	DarkChem Lite v0.1.0
[M+H]+	215.79134	predicted	DeepCCS 1.0 (2019)
[M+Na]+	231.5254766	predicted	DarkChem Lite v0.1.0
[M+Na]+	232.4401766	predicted	DarkChem Lite v0.1.0
[M+Na]+	221.39717	predicted	DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.

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Details1. DNA

Kind

Nucleotide

Organism

Humans

Pharmacological action

Yes

Actions

Intercalation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

References

Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [Article]
Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [Article]
FDA Approved Drug Products: VYXEOS (daunorubicin and cytarabine) liposome for injection, for intravenous use [Link]

Details2. DNA topoisomerase 2-alpha

Kind: Protein
Organism: Humans
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

Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [Article]
Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [Article]
FDA Approved Drug Products: VYXEOS (daunorubicin and cytarabine) liposome for injection, for intravenous use [Link]

Details3. DNA topoisomerase 2-beta

Kind: Protein
Organism: Humans
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

Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [Article]
Zunino F, Capranico G: DNA topoisomerase II as the primary target of anti-tumor anthracyclines. Anticancer Drug Des. 1990 Nov;5(4):307-17. [Article]
FDA Approved Drug Products: VYXEOS (daunorubicin and cytarabine) liposome for injection, for intravenous use [Link]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
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

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. [Article]

Details2. Cytochrome P450 3A5

Kind: Protein
Organism: Humans
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

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. [Article]

Details3. NADPH--cytochrome P450 reductase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inducer

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

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. [Article]

Details4. Cytochrome P450 1B1

Kind: Protein
Organism: Humans
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

Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL: Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41. [Article]

Details5. Aldose reductase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Glyceraldehyde oxidoreductase activity
Specific Function: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Gene Name: AKR1B1
Uniprot ID: P15121
Uniprot Name: Aldose reductase
Molecular Weight: 35853.125 Da

References

Loveless H, Arena E, Felsted RL, Bachur NR: Comparative mammalian metabolism of adriamycin and daunorubicin. Cancer Res. 1978 Mar;38(3):593-8. [Article]

Details6. Carbonyl reductase [NADPH] 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Prostaglandin-e2 9-reductase activity
Specific Function: NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. ...
Gene Name: CBR1
Uniprot ID: P16152
Uniprot Name: Carbonyl reductase [NADPH] 1
Molecular Weight: 30374.73 Da

References

Piska K, Koczurkiewicz P, Bucki A, Wojcik-Pszczola K, Kolaczkowski M, Pekala E: Metabolic carbonyl reduction of anthracyclines - role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents. Invest New Drugs. 2017 Jun;35(3):375-385. doi: 10.1007/s10637-017-0443-2. Epub 2017 Mar 10. [Article]

Details7. Carbonyl reductase [NADPH] 3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Nadph binding
Specific Function: Has low NADPH-dependent oxidoreductase activity towards 4-benzoylpyridine and menadione (in vitro).
Gene Name: CBR3
Uniprot ID: O75828
Uniprot Name: Carbonyl reductase [NADPH] 3
Molecular Weight: 30849.97 Da

References

Piska K, Koczurkiewicz P, Bucki A, Wojcik-Pszczola K, Kolaczkowski M, Pekala E: Metabolic carbonyl reduction of anthracyclines - role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents. Invest New Drugs. 2017 Jun;35(3):375-385. doi: 10.1007/s10637-017-0443-2. Epub 2017 Mar 10. [Article]

Transporters

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	111000	N/A	N/A	A15815

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
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

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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	8000	N/A	N/A	A15963
Ki (nM)	950	N/A	N/A	A15965

Details2. Multidrug resistance-associated protein 1

Kind: Protein
Organism: Humans
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

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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

Details3. Multidrug resistance-associated protein 7

Kind: Protein
Organism: Humans
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

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. [Article]

Details4. ATP-binding cassette sub-family G member 2

Kind: Protein
Organism: Humans
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

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. [Article]
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. [Article]
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. [Article]

Details5. Multidrug resistance-associated protein 6

Kind: Protein
Organism: Humans
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

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. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54

Daunorubicin

Identification

Structure for Daunorubicin (DB00694)

Pharmacology

Interactions

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Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

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Enzymes

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Transporters

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