Identification

Name
Doxorubicin
Accession Number
DB00997
Description

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Doxorubicin binds to nucleic acids, presumably by specific intercalation of the planar anthracycline nucleus with the DNA double helix.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 543.5193
Monoisotopic: 543.174060775
Chemical Formula
C27H29NO11
Synonyms
  • (1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside
  • (8S-cis)-10-((3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione
  • 14-hydroxydaunomycin
  • 14-hydroxydaunorubicine
  • Doxorubicin
  • Doxorubicina
  • Doxorubicine
  • Doxorubicinum
  • Hydroxydaunorubicin

Pharmacology

Indication

Doxorubicin is used to produce regression in disseminated neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms’ tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin’s disease, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

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

Mechanism of action

Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin 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
UNucleolar and coiled-body phosphoprotein 1Not AvailableHumans
Absorption
Not Available
Volume of distribution

The distributive half-life is 5 minutes, which suggests that doxorubicin is rapidly taken up by tissue. Steady state volume of distribution = 809 to 1214 L/m2

Protein binding

Doxorubicin and its major metabolite, doxorubicinol, is 74-76% bound to plasma protein. The extent to binding is independent of plasma concentration up to 1.1 mcg/mL. Doxorubicin does not cross the blood brain barrier.

Metabolism

Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged. Two electron reduction yields doxorubicinol, a secondary alcohol. This pathway is considered the primary metabolic pathway. The one electron reduction is facilitated by several oxidoreductases to form a doxirubicin-semiquinone radical. These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases. Deglycosidation is a minor metabolic pathway (1-2% of the dose undergoes this pathway). The resultant metabolites are deoxyaglycone or hydroxyaglycone formed via reduction or hydrolysis respectively. Enzymes that may be involved with this pathway include xanthine oxidase, NADPH-cytochrome P450 reductase, and cytosolic NADPH dehydrogenase.

Hover over products below to view reaction partners

Route of elimination

40% of the dose appears in bile in 5 days. 5-12% of the drug and its metabolites appears in urine during the same time period. <3% of the dose recovered in urine was doxorubicinol.

Half-life

Terminal half life = 20 - 48 hours.

Clearance
  • 324-809 mL/min/m2 [by metabolism and biliary excretion]
  • 1088 mL/min/m2 [Men]
  • 433 mL/min/m2 [Women]
  • 1540 mL/min/m2 [children greater than 2 years of age receiving administration of 10 to 75 mg/m2 doses]
  • 813 mL/min/m2 [infants younger than 2 years of age receiving administration of 10 to 75 mg/m2 doses]
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

LD50=21800 ug/kg (rat, subcutaneous)

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Doxorubicin Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
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 doxorubicin.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 doxorubicin.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 doxorubicin.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
AbametapirThe serum concentration of Doxorubicin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Abatacept can be increased when combined with Doxorubicin.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Doxorubicin.
AbemaciclibAbemaciclib may decrease the excretion rate of Doxorubicin which could result in a higher serum level.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Doxorubicin.
AcalabrutinibThe metabolism of Doxorubicin can be decreased when combined with Acalabrutinib.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Doxorubicin.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Doxorubicin.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Doxorubicin.
AcetazolamideThe metabolism of Doxorubicin can be decreased when combined with Acetazolamide.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of doxorubicin.
  • Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of doxorubicin.

Products

Product Ingredients
IngredientUNIICASInChI Key
Doxorubicin citrateAJQ2ZNG2WL111266-55-8INEKNBHAPBIAFK-RUELKSSGSA-N
Doxorubicin hydrochloride82F2G7BL4E25316-40-9MWWSFMDVAYGXBV-RUELKSSGSA-N
International/Other Brands
Adriablastina (Pfizer) / Adriblastin (Actavis)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Adriamycin PFSSolutionIntravenous; IntravesicalPfizer Canada Ulc1995-12-31Not applicableCanada flag
Adriamycin RdfPowder, for solutionIntravenousPfizer Canada Ulc1995-12-312006-08-02Canada flag
Adriamycin RdfPowder, for solutionIntravenousPfizer Canada Ulc1996-12-312006-08-02Canada flag
Adriamycin RdfPowder, for solutionIntravenousPfizer Canada Ulc1996-12-312006-08-02Canada flag
Adriamycin Rdf Inj 10mg/vialPowder, for solutionIntravenousCarlo Erba Farmitalia Spa1976-12-311996-09-10Canada flag
Adriamycin Rdf Inj 150mg/vialPowder, for solutionIntravenousAdria Laboratories Of Canada Ltd.1988-12-311996-09-10Canada flag
Adriamycin Rdf Inj 50mg/vialPowder, for solutionIntravenousCarlo Erba Farmitalia Spa1976-12-311996-09-10Canada flag
CaelyxInjection, solution, concentrate2 mg/mlIntravenousJanssen Cilag International Nv1996-06-21Not applicableEU flag
CaelyxInjection, solution, concentrate2 mg/mlIntravenousJanssen Cilag International Nv1996-06-21Not applicableEU flag
CaelyxInjection, solution, concentrate2 mg/mlIntravenousJanssen Cilag International Nv1996-06-21Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdriamycinInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
AdriamycinInjection, solution2 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.1996-05-01Not applicableUS flag
AdriamycinInjection, powder, lyophilized, for solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
AdriamycinInjection, solution2 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.1996-05-01Not applicableUS flag
AdriamycinInjection, powder, lyophilized, for solution2 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2018-01-19Not applicableUS flag
AdriamycinInjection, solution2 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.1996-05-01Not applicableUS flag
AdriamycinInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
AdriamycinInjection, solution2 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.1996-05-01Not applicableUS flag
AdriamycinInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
AdriamycinInjection, powder, lyophilized, for solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-05-012014-06-30US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Doxorubicin HydrochlorideDoxorubicin hydrochloride (2 mg/1mL)Injection, powder, lyophilized, for solutionIntra-arterial; Intravenous; IntravesicalHospira, Inc.2016-04-182017-12-31US flag
LipodoxDoxorubicin hydrochloride (2 mg/1mL)Injectable, liposomalIntravenousSun Pharmaceutical Industries, Inc.2012-02-092015-05-29US flag
Lipodox 50Doxorubicin hydrochloride (2 mg/1mL)Injectable, liposomalIntravenousSun Pharmaceutical Industries, Inc.2012-02-092015-05-29US flag

Categories

ATC Codes
L01DB01 — Doxorubicin
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 13 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 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinone, anthracycline antibiotic, aminoglycoside, deoxy hexoside, anthracycline (CHEBI:28748) / Other Polyketides, Anthracyclinones (C01661) / Anthracyclinones (LMPK13050001)

Chemical Identifiers

UNII
80168379AG
CAS number
23214-92-8
InChI Key
AOJJSUZBOXZQNB-TZSSRYMLSA-N
InChI
InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22+,27-/m0/s1
IUPAC Name
(8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione
SMILES
COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[[email protected]](O)(C[[email protected]@H]3O[[email protected]]3C[[email protected]](N)[[email protected]](O)[[email protected]](C)O3)C(=O)CO)C(O)=C1C2=O

References

Synthesis Reference

Gian P. Vicario, Sergio Penco, Federico Arcamone, "Daunorubicin and doxorubicin labelled with .sup.14 C at the 14-position and processes for their preparation." U.S. Patent US4211864, issued March, 1976.

US4211864
General References
  1. Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86. [PubMed:1462166]
  2. Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA: Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333-53. [PubMed:4290058]
  3. Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C: Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 1969 Nov;11(6):1101-10. [PubMed:5365804]
  4. Di Marco A, Gaetani M, Scarpinato B: Adriamycin (NSC-123,127): a new antibiotic with antitumor activity. Cancer Chemother Rep. 1969 Feb;53(1):33-7. [PubMed:5772652]
  5. Lomovskaya N, Otten SL, Doi-Katayama Y, Fonstein L, Liu XC, Takatsu T, Inventi-Solari A, Filippini S, Torti F, Colombo AL, Hutchinson CR: Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene. J Bacteriol. 1999 Jan;181(1):305-18. [PubMed:9864344]
  6. Mordente A, Meucci E, Silvestrini A, Martorana GE, Giardina B: New developments in anthracycline-induced cardiotoxicity. Curr Med Chem. 2009;16(13):1656-72. [PubMed:19442138]
  7. Minotti G: Reactions of adriamycin with microsomal iron and lipids. Free Radic Res Commun. 1989;7(3-6):143-8. [PubMed:2555273]
Human Metabolome Database
HMDB0015132
KEGG Drug
D03899
KEGG Compound
C01661
PubChem Compound
31703
PubChem Substance
46507641
ChemSpider
29400
BindingDB
32022
RxNav
3639
ChEBI
28748
ChEMBL
CHEMBL53463
ZINC
ZINC000003918087
Therapeutic Targets Database
DNC000163
PharmGKB
PA449412
PDBe Ligand
DM2
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Doxorubicin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
151d / 1d12 / 1da9 / 1i1e / 1p20 / 2dr6 / 4dx7 / 4zvm / 5mra / 5om7
show 2 more
FDA label
Download (105 KB)
MSDS
Download (74.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentAdvanced Follicular Lymphoma1
4Active Not RecruitingTreatmentBreast Cancer1
4Active Not RecruitingTreatmentMultiple Myeloma (MM)1
4Active Not RecruitingTreatmentSoft Tissue Sarcoma (STS)1
4CompletedHealth Services ResearchBreast Cancer1
4CompletedOtherBMI >30 kg/m2 / Breast Cancer1
4CompletedOtherHepato Cellular Carcinoma1
4CompletedPreventionCarcinoma of Urinary Bladder, Superficial1
4CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4CompletedTreatmentAdult Acute Lymphocytic Leukemia4

Pharmacoeconomics

Manufacturers
  • Ortho biotech products lp
  • Pharmacia and upjohn co
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Pharmachemie bv
  • Teva parenteral medicines inc
  • Bristol myers squibb co
Packagers
  • Alza Corp.
  • APP Pharmaceuticals
  • APPD
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bristol-Myers Squibb Co.
  • Centocor Ortho Biotech Inc.
  • Mead Johnson and Co.
  • Pfizer Inc.
  • Pharmachemie BV
  • Pharmacia Inc.
  • Schering-Plough Inc.
  • Sopherion Therapeutics LLC
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous10 mg/5mL
Injection, solution, concentrateIntravenous50 mg/25mL
Injection, solutionParenteral50 MG
Injection, powder, lyophilized, for solutionIntravenous2 mg/1mL
InjectionParenteral10 mg
InjectionParenteral200 mg
InjectionParenteral50 mg
Injection, powder, for solutionParenteral10 MG/5ML
Injection, powder, for solutionParenteral50 MG
Injection, powder, lyophilized, for solutionIntravenous10 mg
Injection, solutionIntravenous10 MG/5ML
Injection, solutionIntravenous200 MG/100ML
Injection, solutionIntravenous50 MG/25ML
Injection
SolutionParenteral10 mg
SolutionParenteral200 mg
SolutionParenteral50 mg
Injection, powder, lyophilized, for solution10 mg
Injection, powder, lyophilized, for solution50 mg
SolutionParenteral2 MG/ML
InjectionIntravenous
Injection, solution, concentrateIntravenous2 mg/ml
Injection, solution, concentrateIntravenous20 mg/10mL
SuspensionIntravenous
Injection, powder, lyophilized, for solutionIntravenous50 mg
Injectable, liposomalIntravenous2 mg/1mL
Injection, suspension, liposomalIntravenous2 mg/1mL
Injection, solutionParenteral10 MG
Injection, solutionParenteral150 MG
PowderParenteral50 MG
InjectionParenteral2 mg/ml
SolutionIntravenous10 mg/5ml
SolutionIntravenous50 mg/25ml
Powder, for solutionIntravenous
SolutionParenteral
Injection, solutionParenteral
InjectionIntravenous10 mg/5mL
InjectionIntravenous2 mg/1mL
InjectionIntravenous20 mg/10mL
InjectionIntravenous200 mg/100mL
InjectionIntravenous50 mg/25mL
Injection, powder, lyophilized, for solutionIntra-arterial; Intravenous; Intravesical2 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1
Injection, powder, lyophilized, for solutionIntravenous150 mg/1
Injection, powder, lyophilized, for solutionIntravenous20 mg/1
Injection, powder, lyophilized, for solutionIntravenous50 mg/1
Injection, solutionIntravenous2 mg/1mL
Powder, for solutionIntravenous; Intravesical
SolutionIntravenous
SolutionIntravenous; Intravesical
Injection, powder, lyophilized, for solutionIntravenous; Intravesical10 mg
Injection, powder, lyophilized, for solutionIntravenous; Intravesical50 mg
PowderParenteral
Injection, solution, concentrateIntravenous; Parenteral2 MG/ML
SolutionIntravenous10 mg
SolutionIntravenous50 mg
Injection, solution, concentrateParenteral10 mg/5ml
Injection, solution, concentrateParenteral50 mg/25ml
Injection, powder, for solutionIntravenous10 mg
SolutionIntravenous2 mg
Injectable, liposomalIntravenous
Injection, powder, for solutionIntravenous50 mg
PowderIntravenous; Parenteral50 MG
InjectionParenteral10 mg/5ml
InjectionParenteral50 mg/25ml
Injection, powder, lyophilized, for solutionIntravenous100 mg/50mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/25mL
SuspensionIntravenous2 mg
Injection, powder, for solution
Prices
Unit descriptionCostUnit
Doxorubicin 50 mg vial132.0USD vial
Doxil 2 mg/ml vial115.78USD ml
Adriamycin 50 mg vial64.8USD vial
Doxorubicin 10 mg vial44.4USD vial
Adriamycin 20 mg vial26.4USD vial
Adriamycin 10 mg vial13.2USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5013556No1991-05-072009-10-20US flag
CA1338702No1998-11-122013-11-12Canada flag
CA1335565No1995-05-162012-05-16Canada flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)229-231 °CPhysProp
water solubilitySolubleNot Available
logP1.27HANSCH,C ET AL. (1995)
Caco2 permeability-6.8ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility1.18 mg/mLALOGPS
logP1.41ALOGPS
logP0.92ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)9.53ChemAxon
pKa (Strongest Basic)8.94ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area206.07 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity134.59 m3·mol-1ChemAxon
Polarizability53.87 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.8092
Blood Brain Barrier-0.9951
Caco-2 permeable-0.799
P-glycoprotein substrateSubstrate0.7861
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.9053
CYP450 2C9 substrateNon-substrate0.8042
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5888
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9209
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8911
Ames testAMES toxic0.9198
CarcinogenicityNon-carcinogens0.9534
BiodegradationNot ready biodegradable0.9672
Rat acute toxicity2.6644 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9752
hERG inhibition (predictor II)Non-inhibitor0.7195
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-006t-0109000000-ac65f689e3fa439adddc

Targets

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. Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA: Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. Mol Pharmacol. 1994 Apr;45(4):649-56. [PubMed:8183243]
  2. Momparler RL, Karon M, Siegel SE, Avila F: Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Res. 1976 Aug;36(8):2891-5. [PubMed:1277199]
  3. Frederick CA, Williams LD, Ughetto G, van der Marel GA, van Boom JH, Rich A, Wang AH: Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin. Biochemistry. 1990 Mar 13;29(10):2538-49. [PubMed:2334681]
Details
2. 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
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Rody A, Karn T, Gatje R, Ahr A, Solbach C, Kourtis K, Munnes M, Loibl S, Kissler S, Ruckhaberle E, Holtrich U, von Minckwitz G, Kaufmann M: Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. Breast. 2007 Feb;16(1):86-93. Epub 2006 Sep 28. [PubMed:17010609]
  3. Koehn H, Magan N, Isaacs RJ, Stowell KM: Differential regulation of DNA repair protein Rad51 in human tumour cell lines exposed to doxorubicin. Anticancer Drugs. 2007 Apr;18(4):419-25. [PubMed:17351394]
  4. Hayashi S, Hatashita M, Matsumoto H, Shioura H, Kitai R, Kano E: Enhancement of radiosensitivity by topoisomerase II inhibitor, amrubicin and amrubicinol, in human lung adenocarcinoma A549 cells and kinetics of apoptosis and necrosis induction. Int J Mol Med. 2006 Nov;18(5):909-15. [PubMed:17016621]
  5. Azarova AM, Lyu YL, Lin CP, Tsai YC, Lau JY, Wang JC, Liu LF: Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11014-9. Epub 2007 Jun 19. [PubMed:17578914]
  6. Menendez JA, Vellon L, Lupu R: DNA topoisomerase IIalpha (TOP2A) inhibitors up-regulate fatty acid synthase gene expression in SK-Br3 breast cancer cells: in vitro evidence for a 'functional amplicon' involving FAS, Her-2/neu and TOP2A genes. Int J Mol Med. 2006 Dec;18(6):1081-7. [PubMed:17089011]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Poly(a) rna binding
Specific Function
Related to nucleologenesis, may play a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus. It has intrinsic GTPase and ATPas...
Gene Name
NOLC1
Uniprot ID
Q14978
Uniprot Name
Nucleolar and coiled-body phosphoprotein 1
Molecular Weight
73602.49 Da
References
  1. Kim YK, Lee WK, Jin Y, Lee KJ, Jeon H, Yu YG: Doxorubicin binds to un-phosphorylated form of hNopp140 and reduces protein kinase CK2-dependent phosphorylation of hNopp140. J Biochem Mol Biol. 2006 Nov 30;39(6):774-81. [PubMed:17129415]

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. Lu H, Chen CS, Waxman DJ: Potentiation of methoxymorpholinyl doxorubicin antitumor activity by P450 3A4 gene transfer. Cancer Gene Ther. 2009 May;16(5):393-404. doi: 10.1038/cgt.2008.93. Epub 2008 Nov 14. [PubMed:19011599]
  2. Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R: Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions. Biochem Pharmacol. 1993 Feb 24;45(4):853-61. [PubMed:8452560]
  3. Diaz Flaque MC, Cayrol MF, Sterle HA, Del Rosario Aschero M, Diaz Albuja JA, Isse B, Farias RN, Cerchietti L, Rosemblit C, Cremaschi GA: Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells. Oncotarget. 2019 Apr 30;10(32):3051-3065. doi: 10.18632/oncotarget.26890. eCollection 2019 Apr 30. [PubMed:31105885]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Le Guellec C, Lacarelle B, Catalin J, Durand A: Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5. [PubMed:8258200]
  2. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Masek V, Anzenbacherova E, Etrych T, Strohalm J, Ulbrich K, Anzenbacher P: Interaction of N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates with human liver microsomal cytochromes P450: comparison with free doxorubicin. Drug Metab Dispos. 2011 Sep;39(9):1704-10. doi: 10.1124/dmd.110.037986. Epub 2011 Jun 3. [PubMed:21642392]
  2. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [PubMed:17101742]
  3. Potential CYP2B6 Substrates, Inhibitors, Inudcers (https://ctep.cancer.gov/protocoldevelopment/docs/cyp2b6.doc) [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
There are limited data in the literature supporting the inhibitory actions of this drug on CYP1B1. The majority of the data suggests that it is an inducer of CYP1B1.
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. Zordoky BN, El-Kadi AO: Induction of several cytochrome P450 genes by doxorubicin in H9c2 cells. Vascul Pharmacol. 2008 Oct-Dec;49(4-6):166-72. doi: 10.1016/j.vph.2008.07.004. Epub 2008 Jul 25. [PubMed:18707023]
  2. 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. [PubMed:11160641]
  3. Zordoky BN, Anwar-Mohamed A, Aboutabl ME, El-Kadi AO: Acute doxorubicin toxicity differentially alters cytochrome P450 expression and arachidonic acid metabolism in rat kidney and liver. Drug Metab Dispos. 2011 Aug;39(8):1440-50. doi: 10.1124/dmd.111.039123. Epub 2011 May 13. [PubMed:21571947]
  4. Grant MK, Seelig DM, Sharkey LC, Zordoky BN: Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice. Biol Sex Differ. 2017 Jan 7;8:1. doi: 10.1186/s13293-016-0124-4. eCollection 2017. [PubMed:28078076]
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. Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [PubMed:18635746]
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. Bains OS, Karkling MJ, Lubieniecka JM, Grigliatti TA, Reid RE, Riggs KW: Naturally occurring variants of human CBR3 alter anthracycline in vitro metabolism. J Pharmacol Exp Ther. 2010 Mar;332(3):755-63. doi: 10.1124/jpet.109.160614. Epub 2009 Dec 9. [PubMed:20007405]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
L-glucuronate reductase activity
Specific Function
Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyd...
Gene Name
AKR1A1
Uniprot ID
P14550
Uniprot Name
Alcohol dehydrogenase [NADP(+)]
Molecular Weight
36572.71 Da
References
  1. Kassner N, Huse K, Martin HJ, Godtel-Armbrust U, Metzger A, Meineke I, Brockmoller J, Klein K, Zanger UM, Maser E, Wojnowski L: Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20. doi: 10.1124/dmd.108.022251. Epub 2008 Jul 17. [PubMed:18635746]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2....
Gene Name
AKR1C3
Uniprot ID
P42330
Uniprot Name
Aldo-keto reductase family 1 member C3
Molecular Weight
36852.89 Da
References
  1. Novotna R, Wsol V, Xiong G, Maser E: Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6. doi: 10.1016/j.toxlet.2008.06.858. Epub 2008 Jun 21. [PubMed:18616992]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Superoxide dismutase activity
Specific Function
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vit...
Gene Name
NQO1
Uniprot ID
P15559
Uniprot Name
NAD(P)H dehydrogenase [quinone] 1
Molecular Weight
30867.405 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [PubMed:12688675]
  2. Niitsu N, Kasukabe T, Yokoyama A, Okabe-Kado J, Yamamoto-Yamaguchi Y, Umeda M, Honma Y: Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. Mol Pharmacol. 2000 Jul;58(1):27-36. [PubMed:10860924]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [PubMed:12688675]
  2. Niitsu N, Kasukabe T, Yokoyama A, Okabe-Kado J, Yamamoto-Yamaguchi Y, Umeda M, Honma Y: Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity. Mol Pharmacol. 2000 Jul;58(1):27-36. [PubMed:10860924]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. P...
Gene Name
NOS1
Uniprot ID
P29475
Uniprot Name
Nitric oxide synthase, brain
Molecular Weight
160969.095 Da
References
  1. Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [PubMed:9333325]
  2. Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [PubMed:15054088]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity ...
Gene Name
NOS2
Uniprot ID
P35228
Uniprot Name
Nitric oxide synthase, inducible
Molecular Weight
131116.3 Da
References
  1. Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [PubMed:9333325]
  2. Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [PubMed:15054088]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induce...
Gene Name
NOS3
Uniprot ID
P29474
Uniprot Name
Nitric oxide synthase, endothelial
Molecular Weight
133287.62 Da
References
  1. Vasquez-Vivar J, Martasek P, Hogg N, Masters BS, Pritchard KA Jr, Kalyanaraman B: Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry. 1997 Sep 23;36(38):11293-7. [PubMed:9333325]
  2. Fogli S, Nieri P, Breschi MC: The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. [PubMed:15054088]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Ubiquitin protein ligase binding
Specific Function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name
NDUFS2
Uniprot ID
O75306
Uniprot Name
NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
Molecular Weight
52545.26 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [PubMed:12688675]
  2. Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [PubMed:2850270]
  3. Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [PubMed:9618942]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Nadh dehydrogenase activity
Specific Function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name
NDUFS3
Uniprot ID
O75489
Uniprot Name
NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
Molecular Weight
30241.245 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [PubMed:12688675]
  2. Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [PubMed:2850270]
  3. Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [PubMed:9618942]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Quinone binding
Specific Function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the tra...
Gene Name
NDUFS7
Uniprot ID
O75251
Uniprot Name
NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
Molecular Weight
23563.3 Da
References
  1. Pawlowska J, Tarasiuk J, Wolf CR, Paine MJ, Borowski E: Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52. [PubMed:12688675]
  2. Thornalley PJ, Bannister WH, Bannister JV: Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. Free Radic Res Commun. 1986;2(3):163-71. [PubMed:2850270]
  3. Nohl H, Gille L, Staniek K: The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines. Z Naturforsch C. 1998 Mar-Apr;53(3-4):279-85. [PubMed:9618942]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name
POR
Uniprot ID
P16435
Uniprot Name
NADPH--cytochrome P450 reductase
Molecular Weight
76689.12 Da
References
  1. Gutierrez PL, Gee MV, Bachur NR: Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75. [PubMed:6305277]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Kratz F, Mansour A, Soltau J, Warnecke A, Fichtner I, Unger C, Drevs J: Development of albumin-binding doxorubicin prodrugs that are cleaved by prostate-specific antigen. Arch Pharm (Weinheim). 2005 Oct;338(10):462-72. [PubMed:16211657]
  2. Schmid B, Chung DE, Warnecke A, Fichtner I, Kratz F: Albumin-binding prodrugs of camptothecin and doxorubicin with an Ala-Leu-Ala-Leu-linker that are cleaved by cathepsin B: synthesis and antitumor efficacy. Bioconjug Chem. 2007 May-Jun;18(3):702-16. Epub 2007 Mar 23. [PubMed:17378599]

Transporters

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. Fardel O, Lecureur V, Daval S, Corlu A, Guillouzo A: Up-regulation of P-glycoprotein expression in rat liver cells by acute doxorubicin treatment. Eur J Biochem. 1997 May 15;246(1):186-92. [PubMed:9210482]
  2. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. [PubMed:11405287]
  3. Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. [PubMed:10746169]
  4. Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H: Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux. Pharmacol Res. 2010 Jan;61(1):76-84. doi: 10.1016/j.phrs.2009.07.002. Epub 2009 Jul 21. [PubMed:19631272]
  5. Li D, Jang SH, Kim J, Wientjes MG, Au JL: Enhanced drug-induced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res. 2003 Jan;20(1):45-50. [PubMed:12608535]
  6. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [PubMed:12948019]
  7. Kim S, Kim SS, Bang YJ, Kim SJ, Lee BJ: In vitro activities of native and designed peptide antibiotics against drug sensitive and resistant tumor cell lines. Peptides. 2003 Jul;24(7):945-53. [PubMed:14499271]
  8. Ambudkar SV, Lelong IH, Zhang J, Cardarelli CO, Gottesman MM, Pastan I: Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8472-6. [PubMed:1356264]
  9. Kusunoki N, Takara K, Tanigawara Y, Yamauchi A, Ueda K, Komada F, Ku Y, Kuroda Y, Saitoh Y, Okumura K: Inhibitory effects of a cyclosporin derivative, SDZ PSC 833, on transport of doxorubicin and vinblastine via human P-glycoprotein. Jpn J Cancer Res. 1998 Nov;89(11):1220-8. [PubMed:9914792]
  10. Li YC, Fung KP, Kwok TT, Lee CY, Suen YK, Kong SK: Mitochondria-targeting drug oligomycin blocked P-glycoprotein activity and triggered apoptosis in doxorubicin-resistant HepG2 cells. Chemotherapy. 2004 Jun;50(2):55-62. [PubMed:15211078]
  11. Sieczkowski E, Lehner C, Ambros PF, Hohenegger M: Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. Int J Cancer. 2010 May 1;126(9):2025-35. doi: 10.1002/ijc.24885. [PubMed:19739078]
  12. Bray J, Sludden J, Griffin MJ, Cole M, Verrill M, Jamieson D, Boddy AV: Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Br J Cancer. 2010 Mar 16;102(6):1003-9. doi: 10.1038/sj.bjc.6605587. Epub 2010 Feb 23. [PubMed:20179710]
  13. Tao LY, Liang YJ, Wang F, Chen LM, Yan YY, Dai CL, Fu LW: Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. Cancer Chemother Pharmacol. 2009 Oct;64(5):961-9. doi: 10.1007/s00280-009-0949-1. Epub 2009 Mar 3. [PubMed:19255759]
  14. Woodahl EL, Crouthamel MH, Bui T, Shen DD, Ho RJ: MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8. doi: 10.1007/s00280-008-0906-4. Epub 2009 Jan 4. [PubMed:19123050]
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. [PubMed:8621644]
  2. Godinot N, Iversen PW, Tabas L, Xia X, Williams DC, Dantzig AH, Perry WL 3rd: Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey. Mol Cancer Ther. 2003 Mar;2(3):307-16. [PubMed:12657726]
  3. Tribull TE, Bruner RH, Bain LJ: The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury. Toxicol Lett. 2003 Apr 30;142(1-2):61-70. [PubMed:12765240]
  4. Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG: Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos. 2003 Aug;31(8):1016-26. [PubMed:12867490]
  5. Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SP, Deeley RG: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53. [PubMed:9281595]
  6. Wong IL, Chan KF, Tsang KH, Lam CY, Zhao Y, Chan TH, Chow LM: Modulation of multidrug resistance protein 1 (MRP1/ABCC1)-mediated multidrug resistance by bivalent apigenin homodimers and their derivatives. J Med Chem. 2009 Sep 10;52(17):5311-22. doi: 10.1021/jm900194w. [PubMed:19725578]
  7. Tao LY, Liang YJ, Wang F, Chen LM, Yan YY, Dai CL, Fu LW: Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. Cancer Chemother Pharmacol. 2009 Oct;64(5):961-9. doi: 10.1007/s00280-009-0949-1. Epub 2009 Mar 3. [PubMed:19255759]
  8. Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [PubMed:19390592]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [PubMed:11585759]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Cai J, Daoud R, Alqawi O, Georges E, Pelletier J, Gros P: Nucleotide binding and nucleotide hydrolysis properties of the ABC transporter MRP6 (ABCC6). Biochemistry. 2002 Jun 25;41(25):8058-67. [PubMed:12069597]
  2. Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD: Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. [PubMed:12414644]
Kind
Protein
Organism
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. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y: ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003 Jun 20;278(25):22644-9. Epub 2003 Apr 7. [PubMed:12682043]
  2. Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. [PubMed:12488537]
  3. Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B: Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7. [PubMed:11437380]
  4. Allen JD, Van Dort SC, Buitelaar M, van Tellingen O, Schinkel AH: Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003 Mar 15;63(6):1339-44. [PubMed:12649196]
  5. An Y, Ongkeko WM: ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1529-42. doi: 10.1517/17425250903228834. [PubMed:19708828]
  6. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [PubMed:19427995]
  7. Dai CL, Liang YJ, Wang YS, Tiwari AK, Yan YY, Wang F, Chen ZS, Tong XZ, Fu LW: Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009 Jun 28;279(1):74-83. doi: 10.1016/j.canlet.2009.01.027. Epub 2009 Feb 18. [PubMed:19232821]
  8. Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [PubMed:19390592]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic cation transmembrane transporter activity
Specific Function
High affinity carnitine transporter; the uptake is partially sodium-ion dependent. Thought to mediate the L-carnitine secretion mechanism from testis epididymal epithelium into the lumen which is i...
Gene Name
SLC22A16
Uniprot ID
Q86VW1
Uniprot Name
Solute carrier family 22 member 16
Molecular Weight
64613.58 Da
References
  1. Bray J, Sludden J, Griffin MJ, Cole M, Verrill M, Jamieson D, Boddy AV: Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Br J Cancer. 2010 Mar 16;102(6):1003-9. doi: 10.1038/sj.bjc.6605587. Epub 2010 Feb 23. [PubMed:20179710]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [PubMed:12527806]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Not Available
Gene Name
ABCB8
Uniprot ID
Q9NUT2
Uniprot Name
ATP-binding cassette sub-family B member 8, mitochondrial
Molecular Weight
79988.17 Da
References
  1. Elliott AM, Al-Hajj MA: ABCB8 mediates doxorubicin resistance in melanoma cells by protecting the mitochondrial genome. Mol Cancer Res. 2009 Jan;7(1):79-87. doi: 10.1158/1541-7786.MCR-08-0235. [PubMed:19147539]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [PubMed:12739759]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transmembrane transporter activity
Specific Function
Can activate specifically hydrolysis of GTP bound to RAC1 and CDC42, but not RALA. Mediates ATP-dependent transport of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin (DOX) and is the ma...
Gene Name
RALBP1
Uniprot ID
Q15311
Uniprot Name
RalA-binding protein 1
Molecular Weight
76062.86 Da
References
  1. Singhal SS, Singhal J, Nair MP, Lacko AG, Awasthi YC, Awasthi S: Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25. [PubMed:17273774]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Folmer Y, Schneider M, Blum HE, Hafkemeyer P: Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-ABCC2 antisense constructs. Cancer Gene Ther. 2007 Nov;14(11):875-84. Epub 2007 Aug 17. [PubMed:17704753]

Drug created on June 13, 2005 07:24 / Updated on October 25, 2020 09:16

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