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
Thumb
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
  • Daunorubicina
  • Daunorubicine
  • Daunorubicinum
  • Leukaemomycin C
  • Rubidomycin
External IDs
  • DNR
  • FI 6339
  • NSC 82151
  • RCRA Waste No. U059
  • RP 13057
  • RP-13057

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

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
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

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
Adverseeffects
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Toxicity

Not Available

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
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.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Daunorubicin is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Daunorubicin.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Daunorubicin.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Daunorubicin.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Daunorubicin.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Daunorubicin.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Daunorubicin.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Daunorubicin.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Daunorubicin.
AfatinibAfatinib may decrease the excretion rate of Daunorubicin which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Daunorubicin citrate5L84T2Z6NP371770-68-2VNTHYLVDGVBPOU-QQYBVWGSSA-N
Daunorubicin hydrochlorideUD984I04LZ23541-50-6GUGHGUXZJWAIAS-UHFFFAOYSA-N
International/Other Brands
Cerubidin (Sanofi-Aventis) / Cérubidine (Sanofi-Aventis) / Daunoblastin (Pfizer) / Daunoblastina (Pfizer) / Daunorrubicina (GP-Pharm) / Maxidauno (Varifarma)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CerubidinePowder, for solution20 mg / vialIntravenousErfa Canada 2012 Inc1971-12-31Not applicableCanada flag
Daunorubicin HydrochlorideInjection, powder, for solution20 mg/1Intravenoussanofi-aventis U.S. LLC2014-06-232014-11-11US flag
Daunorubicin HydrochlorideInjection5 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2018-01-02Not applicableUS flag
Daunorubicin HydrochlorideInjection5 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2018-01-02Not applicableUS flag
Daunorubicin Hydrochloride for InjectionPowder, for solution20 mg / vialIntravenousTEVA Canada Limited1998-03-042018-04-30Canada flag
Daunorubicin Injectable SolutionSolution50 mg / 10 mLIntravenousGeneric Medical Partners IncNot applicableNot applicableCanada flag
Daunorubicin Injectable SolutionSolution20 mg / 4 mLIntravenousGeneric Medical Partners IncNot applicableNot applicableCanada flag
DaunoXomeInjection, lipid complex2 mg/1mLIntravenousGalen US Inc2012-02-132016-04-16US flag
DaunoXomeInjection, lipid complex2 mg/1mLIntravenousGilead Sciences1996-04-082011-07-01US flag
Daunoxome Liposomal - IV 2mg/ml, 50mg/vialSuspension2 mg / mLIntravenousGilead Sciences1997-09-222001-09-21Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CerubidineInjection, powder, for solution20 mg/4mLIntravenousBedford Pharmaceuticals1998-06-012013-09-30US flag
Daunorubicin HydrochlorideInjection, solution5 mg/1mLIntravenousBedford Pharmaceuticals1998-07-132012-10-31US flag
Daunorubicin HydrochlorideInjection, solution5 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2004-04-012016-06-30US flag
Daunorubicin HydrochlorideInjection, solution5 mg/1mLIntravenousHisun Pharmaceuticals Usa, Inc.2020-01-20Not applicableUS flag
Daunorubicin HydrochlorideInjection5 mg/1mLIntravenousBedford Pharmaceuticals1998-06-012013-09-30US flag
Daunorubicin HydrochlorideInjection, powder, for solution20 mg/4mLIntravenousHisun Pharmaceuticals Usa, Inc.2019-04-252019-09-12US flag
Daunorubicin HydrochlorideInjection, powder, lyophilized, for solution5 mg/1mLIntravenousBedford Pharmaceuticals1996-06-282013-04-30US flag
Daunorubicin HydrochlorideInjection, solution5 mg/1mLIntravenousHisun Pharmaceuticals Usa, Inc.2020-01-20Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
VyxeosDaunorubicin (44 mg) + Cytarabine (100 mg)PowderIntravenousJazz Pharmaceuticals Ireland Limited2021-07-06Not applicableCanada flag
VyxeosDaunorubicin (44 mg/20mL) + Cytarabine (100 mg/20mL)Injection, powder, lyophilized, for suspensionIntravenousJazz Pharmaceuticals, Inc.2017-08-03Not applicableUS flag
Vyxeos LiposomalDaunorubicin hydrochloride (2.2 mg/ml) + Cytarabine (5 mg/ml)Injection, powder, for solutionIntravenousJazz Pharmaceuticals Ireland Limited2020-12-16Not applicableEU flag
Vyxeos LiposomalDaunorubicin hydrochloride (2.2 mg/ml) + Cytarabine (5 mg/ml)Injection, powder, for solutionIntravenousJazz Pharmaceuticals Ireland Limited2020-12-16Not applicableEU flag
Vyxeos LiposomalDaunorubicin hydrochloride (2.2 mg/ml) + Cytarabine (5 mg/ml)Injection, powder, for solutionIntravenousJazz Pharmaceuticals Ireland Limited2020-12-16Not applicableEU flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Daunorubicin HydrochlorideDaunorubicin hydrochloride (20 mg/1)Injection, powder, for solutionIntravenoussanofi-aventis U.S. LLC2014-06-232014-11-11US flag

Categories

ATC Codes
L01DB02 — DaunorubicinL01XY01 — Cytarabine and daunorubicin
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,2-aminoalcohol / 1,4-anthraquinone / 9,10-anthraquinone / Acetal / Alcohol / Alkyl aryl ether / Alpha-hydroxy ketone / Amine / Amino saccharide / Aminoglycoside core
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinone, aminoglycoside antibiotic, anthracycline (CHEBI:41977) / Anthracyclinones (C01907) / Anthracyclinones (LMPK13050002)
Affected organisms
  • Humans and other mammals

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
  1. 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]
  2. 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]
  3. 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]
  4. Saleem T, Kasi A: Daunorubicin . [Article]
  5. FDA Approved Drug Products: VYXEOS (daunorubicin and cytarabine) injection [Link]
  6. Health Canada Approved Drug Products: daunorubicin solution for injection [Link]
  7. FDA Approved Drug Products: Daunorubicin hydrochloride injection [Link]
Human Metabolome Database
HMDB0014832
KEGG Drug
D07776
KEGG Compound
C01907
PubChem Compound
30323
PubChem Substance
46508433
ChemSpider
28163
BindingDB
32017
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 6 more
MSDS
Download (36.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionAcute Myeloid Leukemia (AML)1
4Active Not RecruitingTreatmentAcute Promyelocytic Leukemia (APL)1
4CompletedTreatmentAcute Lymphobkastic Leukemia1
4CompletedTreatmentAcute Lymphoblastic Leukemia (ALL)5
4CompletedTreatmentLeukemia, Lymphocytic, Acute, Adult3
4CompletedTreatmentLeukemias1
4CompletedTreatmentLymphoma, Lymphoblastic1
4RecruitingTreatmentAcute Myeloid Leukemia (AML)1
4Unknown StatusPreventionAcute Promyelocytic Leukemia (APL)1
4Unknown StatusTreatmentAcute Lymphoblastic Leukemia (ALL)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
FormRouteStrength
Injection, powder, for solutionIntravenous20 mg/4mL
Powder, for solutionIntravenous20 mg / vial
Injection, solutionParenteral
Injection, powder, for solutionParenteral20 MG/10ML
Injection, powder, for solutionIntravenous
InjectionIntravenous
Injection, powder, for solutionIntravenous20 mg
Injection, powder, for solution
Injection, powder, lyophilized, for solutionIntravenous
InjectionIntravenous5 mg/1mL
Injection, powder, for solutionIntravenous20 mg/1
Injection, powder, lyophilized, for solutionIntravenous5 mg/1mL
Injection, solutionIntravenous5 mg/1mL
SolutionIntravenous20 mg / 4 mL
SolutionIntravenous50 mg / 10 mL
Injection, powder, lyophilized, for solutionIntravenous20 mg
Injection, lipid complexIntravenous2 mg/1mL
SuspensionIntravenous2 mg / mL
Injection, powder, lyophilized, for suspensionIntravenous
PowderIntravenous
Injection, powder, for solutionIntravenous
PowderIntravenous; Parenteral
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)Region
US7850990No2010-12-142027-01-23US flag
US8022279No2011-09-202027-09-14US flag
US8431806No2013-04-302025-04-22US flag
US8092828No2012-01-102029-04-01US flag
US8518437No2013-08-272026-06-07US flag
US9271931No2016-03-012027-01-23US flag
US10028912No2018-07-242034-09-29US flag
US10166184No2019-01-012032-10-15US flag
US10835492No2020-11-172032-10-15US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)208-209 °CPhysProp
boiling point (°C)190 °CPubChem
water solubility30000 mg/L at 25 °CPubChem
logP1.83SANGSTER (1993)
pKa7.85PubChem
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

Targets

Drugtargets2
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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
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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
  1. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [Article]
  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. [Article]
  3. FDA Approved Drug Products: VYXEOS (daunorubicin and cytarabine) injection [Link]
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
  1. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [Article]
  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. [Article]
  3. FDA Approved Drug Products: VYXEOS (daunorubicin and cytarabine) injection [Link]
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
  1. Aubel-Sadron G, Londos-Gagliardi D: Daunorubicin and doxorubicin, anthracycline antibiotics, a physicochemical and biological review. Biochimie. 1984 May;66(5):333-52. [Article]
  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. [Article]
  3. FDA Approved Drug Products: VYXEOS (daunorubicin and cytarabine) injection [Link]

Enzymes

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
  1. 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]
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
  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. [Article]
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
  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. [Article]
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
  1. 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]
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
  1. Loveless H, Arena E, Felsted RL, Bachur NR: Comparative mammalian metabolism of adriamycin and daunorubicin. Cancer Res. 1978 Mar;38(3):593-8. [Article]
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
  1. 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]
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
  1. 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

Details
1. 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
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
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
  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. [Article]
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
  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. [Article]
  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. [Article]
  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. [Article]
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
  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. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 28, 2021 11:56