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Identification
NameDoxorubicin
Accession NumberDB00997  (APRD00185)
TypeSmall Molecule
GroupsApproved, Investigational
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.

Structure
Thumb
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-alpha-L-lyxo-hexopyranoside
(8S-cis)-10-((3-amino-2,3,6-Trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione
14-hydroxydaunomycin
14-hydroxydaunorubicine
Adriamycin
Doxorubicin
Doxorubicine
Doxorubicinum
Hydroxydaunorubicin
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Adriamycin PFSsolution2 mgintravenous; intravesicalPfizer Canada Inc1995-12-31Not applicableCanada
Adriamycin Rdfpowder for solution10 mgintravenousPfizer Canada Inc1996-12-312006-08-02Canada
Adriamycin Rdfpowder for solution150 mgintravenousPfizer Canada Inc1996-12-312006-08-02Canada
Adriamycin Rdfpowder for solution50 mgintravenousPfizer Canada Inc1995-12-312006-08-02Canada
Adriamycin Rdf Inj 10mg/vialpowder for solution10 mgintravenousCarlo Erba Farmitalia Spa1976-12-311996-09-10Canada
Adriamycin Rdf Inj 150mg/vialpowder for solution150 mgintravenousAdria Laboratories Of Canada Ltd.1988-12-311996-09-10Canada
Adriamycin Rdf Inj 50mg/vialpowder for solution50 mgintravenousCarlo Erba Farmitalia Spa1976-12-311996-09-10Canada
Caelyxsuspension2 mgintravenousJanssen Inc1998-08-19Not applicableCanada
Doxilinjection, suspension, liposomal2 mg/mLintravenousJanssen Products, LP1995-11-172016-04-05Us
Doxorubicinsolution2 mgintravenous; intravesicalPfizer Canada Inc2014-05-21Not applicableCanada
Doxorubicin HCl for Inj. U.S.P. 10mg/vialpowder for solution10 mgintravenousDavid Bull Laboratories (Pty) Ltd.1995-12-311998-08-13Canada
Doxorubicin HCl for Inj. U.S.P. 150mg/vialpowder for solution150 mgintravenousDavid Bull Laboratories (Pty) Ltd.1995-12-311997-08-14Canada
Doxorubicin HCl for Inj. U.S.P. 50mg/vialpowder for solution50 mgintravenousDavid Bull Laboratories (Pty) Ltd.1995-12-311997-08-14Canada
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2013-03-052016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc1987-12-232016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2014-03-172016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2014-03-172016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2014-03-172016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2013-03-172016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2013-03-052016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc1987-12-232016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2013-03-052016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc1987-12-232016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2013-03-052016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc1987-12-232016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2013-03-052016-04-23Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc1987-12-232016-04-23Us
Doxorubicin Hydrochloride for Injection USPpowder for solution50 mgintravenousHospira Healthcare Corporation1997-07-30Not applicableCanada
Doxorubicin Hydrochloride for Injection USPpowder for solution10 mgintravenousHospira Healthcare Corporation1998-03-12Not applicableCanada
Doxorubicin Hydrochloride for Injection USPpowder for solution150 mgintravenousHospira Healthcare Corporation1997-05-08Not applicableCanada
Doxorubicin Hydrochloride Injectionsolution2 mgintravenous; intravesicalTeva Canada Limited2014-02-27Not applicableCanada
Doxorubicin Hydrochloride Injectionsolution2 mgintravenous; intravesicalSandoz Canada Incorporated2015-04-10Not applicableCanada
Doxorubicin Hydrochloride Injectionsolution2 mgintravenousNovopharm Limited1997-09-12Not applicableCanada
Doxorubicin Hydrochloride Injectionsolution2 mgintravenous; intravesicalOmega Laboratories LtdNot applicableNot applicableCanada
Doxorubicin Hydrochloride Injection, USPsolution2 mgintravenous; intravesicalMylan Pharmaceuticals Ulc2015-01-08Not applicableCanada
Doxorubicin Injectionsolution2 mgintravenous; intravesicalAccord Healthcare Inc2014-12-16Not applicableCanada
Myocetliposomes2 mgintravenousSopherion Therapeutics Llc2001-12-21Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Doxorubicin Hydrochlorideinjectable, liposomal2 mg/mLintravenousSun Pharma Global FZE2013-02-052016-04-05Us
Doxorubicin Hydrochlorideinjection, powder, lyophilized, for solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2011-10-292016-04-23Us
Doxorubicin Hydrochlorideinjection10 mg/5mLintravenousMylan Institutional LLC2012-02-142016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousFresenius Kabi USA, LLC2000-04-142016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousFresenius Kabi USA, LLC2000-06-142016-04-05Us
Doxorubicin Hydrochlorideinjectable, liposomal2 mg/mLintravenousSun Pharma Global FZE2013-02-052016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousSun Pharmaceutical Industries Limited2012-02-202016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousActavis Pharma, Inc.2014-11-012016-04-05Us
Doxorubicin Hydrochlorideinjection, powder, lyophilized, for solution2 mg/mLintravenousMylan Institutional LLC2011-10-292016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousSun Pharmaceutical Industries Limited2012-02-202016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousSagent Pharmaceuticals2013-10-312016-04-05Us
Doxorubicin Hydrochlorideinjection, powder, lyophilized, for solution2 mg/mLintravenousMylan Institutional LLC2011-10-292016-04-05Us
Doxorubicin Hydrochlorideinjection10 mg/5mLintravenousAmneal Agila, Llc2013-04-302016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousTeva Parenteral Medicines, Inc.1995-09-012016-04-05Us
Doxorubicin Hydrochlorideinjection200 mg/100mLintravenousMylan Institutional LLC2012-02-142016-04-05Us
Doxorubicin Hydrochlorideinjection200 mg/100mLintravenousAmneal Agila, Llc2013-04-302016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousTeva Parenteral Medicines, Inc.1995-09-012016-04-05Us
Doxorubicin Hydrochlorideinjection50 mg/25mLintravenousMylan Institutional LLC2012-02-142016-04-05Us
Doxorubicin Hydrochlorideinjection50 mg/25mLintravenousAmneal Agila, Llc2013-04-302016-04-05Us
Doxorubicin Hydrochlorideinjection, solution2 mg/mLintravenousTeva Parenteral Medicines, Inc.1996-09-012016-04-05Us
Doxorubicin Hydrochlorideinjection20 mg/10mLintravenousMylan Institutional LLC2012-02-142016-04-05Us
Doxorubicin Hydrochlorideinjection20 mg/10mLintravenousAmneal Agila, Llc2013-04-302016-04-05Us
Doxorubicin Hydrochlorideinjection, powder, lyophilized, for solution2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2011-10-292016-04-23Us
Over the Counter ProductsNot Available
International Brands
NameCompany
AdriablastinaPfizer
AdriamycinPfizer
AdriblastinActavis
RubexNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Doxorubicin Hydrochloride
Thumb
  • InChI Key: MWWSFMDVAYGXBV-BADIEKLNSA-N
  • Monoisotopic Mass: 579.150738514
  • Average Mass: 579.98
DBSALT000060
Categories
UNII80168379AG
CAS number23214-92-8
WeightAverage: 543.5193
Monoisotopic: 543.174060775
Chemical FormulaC27H29NO11
InChI KeyInChIKey=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[C@](O)(C[C@@H]3O[[email protected]]3C[[email protected]](N)[[email protected]](O)[[email protected]](C)O3)C(=O)CO)C(O)=C1C2=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassAnthracyclines
Sub ClassNot Available
Direct ParentAnthracyclines
Alternative Parents
Substituents
  • Anthracyclinone-skeleton
  • Anthracycline
  • Tetracenequinone
  • 1,4-anthraquinone
  • 9,10-anthraquinone
  • Anthracene
  • Amino sugar
  • Tetralin
  • Aryl ketone
  • Hydroquinone
  • Anisole
  • Amino saccharide
  • Alkyl aryl ether
  • Benzenoid
  • Oxane
  • Monosaccharide
  • Vinylogous acid
  • Tertiary alcohol
  • Alpha-hydroxy ketone
  • Secondary alcohol
  • Polyol
  • Ketone
  • 1,2-aminoalcohol
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Acetal
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationDoxorubicin 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.
PharmacodynamicsDoxorubicin 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 actionDoxorubicin 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.
Related Articles
AbsorptionNot 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 bindingDoxorubicin 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.

SubstrateEnzymesProduct
Doxorubicin
DoxorubicinolDetails
Doxorubicin
Doxorubicin-semiquinoneDetails
Doxorubicin
Doxorubicinol deoxaglyconeDetails
Doxorubicin
Not Available
Doxorubicine hydroxyaglyconeDetails
Doxorubicine hydroxyaglycone
Not Available
Doxirubicinol hydroxyaglyconeDetails
Route of elimination40% 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 lifeTerminal 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]
ToxicityLD50=21800 ug/kg (rat, subcutaneous)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Doxorubicin Metabolism PathwayDrug metabolismSMP00650
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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
Dosage forms
FormRouteStrength
Solutionintravenous; intravesical2 mg
Suspensionintravenous2 mg
Injection, suspension, liposomalintravenous2 mg/mL
Injectable, liposomalintravenous2 mg/mL
Injectionintravenous10 mg/5mL
Injectionintravenous20 mg/10mL
Injectionintravenous200 mg/100mL
Injectionintravenous50 mg/25mL
Injection, powder, lyophilized, for solutionintravenous2 mg/mL
Injection, solutionintravenous2 mg/mL
Powder for solutionintravenous10 mg
Powder for solutionintravenous150 mg
Powder for solutionintravenous50 mg
Solutionintravenous2 mg
Liposomesintravenous2 mg
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)
CA1335565 No1995-05-162012-05-16Canada
CA1338702 No1998-11-122013-11-12Canada
US5013556 No1992-10-202009-10-20Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point229-231 °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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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 ]
External Links
ATC CodesL01DB01
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (105 KB)
MSDSDownload (74.1 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Doxorubicin can be increased when it is combined with Abiraterone.
AmiodaroneThe serum concentration of Doxorubicin can be increased when it is combined with Amiodarone.
AprepitantThe serum concentration of Doxorubicin can be increased when it is combined with Aprepitant.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Doxorubicin.
ArtemetherThe serum concentration of Doxorubicin can be increased when it is combined with Artemether.
AtazanavirThe serum concentration of Doxorubicin can be increased when it is combined with Atazanavir.
AtorvastatinThe serum concentration of Doxorubicin can be increased when it is combined with Atorvastatin.
AzithromycinThe serum concentration of Doxorubicin can be increased when it is combined with Azithromycin.
BevacizumabBevacizumab may increase the cardiotoxic activities of Doxorubicin.
BexaroteneThe serum concentration of Doxorubicin can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Doxorubicin can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Doxorubicin can be decreased when it is combined with Bosentan.
BupropionThe serum concentration of Doxorubicin can be increased when it is combined with Bupropion.
CabazitaxelThe metabolism of Doxorubicin can be decreased when combined with Cabazitaxel.
CarbamazepineThe serum concentration of Doxorubicin can be decreased when it is combined with Carbamazepine.
CarvedilolThe serum concentration of Doxorubicin can be increased when it is combined with Carvedilol.
CelecoxibThe serum concentration of Doxorubicin can be increased when it is combined with Celecoxib.
CeritinibThe serum concentration of Doxorubicin can be increased when it is combined with Ceritinib.
ChloroquineThe serum concentration of Doxorubicin can be increased when it is combined with Chloroquine.
ChlorpromazineThe serum concentration of Doxorubicin can be increased when it is combined with Chlorpromazine.
CimetidineThe serum concentration of Doxorubicin can be increased when it is combined with Cimetidine.
CinacalcetThe serum concentration of Doxorubicin can be increased when it is combined with Cinacalcet.
ClarithromycinThe serum concentration of Doxorubicin can be increased when it is combined with Clarithromycin.
ClobazamThe serum concentration of Doxorubicin can be increased when it is combined with Clobazam.
ClomipramineThe serum concentration of Doxorubicin can be increased when it is combined with Clomipramine.
ClozapineThe risk or severity of adverse effects can be increased when Doxorubicin is combined with Clozapine.
CobicistatThe serum concentration of Doxorubicin can be increased when it is combined with Cobicistat.
CocaineThe serum concentration of Doxorubicin can be increased when it is combined with Cocaine.
ConivaptanThe serum concentration of Doxorubicin can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Doxorubicin can be increased when it is combined with Crizotinib.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Doxorubicin.
CyclosporineThe serum concentration of Doxorubicin can be increased when it is combined with Cyclosporine.
DabrafenibThe serum concentration of Doxorubicin can be decreased when it is combined with Dabrafenib.
DaclatasvirThe serum concentration of Doxorubicin can be increased when it is combined with Daclatasvir.
DarifenacinThe serum concentration of Doxorubicin can be increased when it is combined with Darifenacin.
DarunavirThe serum concentration of Doxorubicin can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Doxorubicin can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Doxorubicin can be decreased when it is combined with Deferasirox.
DelavirdineThe serum concentration of Doxorubicin can be increased when it is combined with Delavirdine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Doxorubicin.
DesipramineThe serum concentration of Doxorubicin can be increased when it is combined with Desipramine.
DexrazoxaneThe therapeutic efficacy of Doxorubicin can be decreased when used in combination with Dexrazoxane.
DigoxinDigoxin may decrease the cardiotoxic activities of Doxorubicin.
DiltiazemThe serum concentration of Doxorubicin can be increased when it is combined with Diltiazem.
DiphenhydramineThe serum concentration of Doxorubicin can be increased when it is combined with Diphenhydramine.
DipyridamoleThe serum concentration of Doxorubicin can be increased when it is combined with Dipyridamole.
DronedaroneThe serum concentration of Doxorubicin can be increased when it is combined with Dronedarone.
DuloxetineThe serum concentration of Doxorubicin can be increased when it is combined with Duloxetine.
EliglustatThe serum concentration of Doxorubicin can be increased when it is combined with Eliglustat.
EnzalutamideThe serum concentration of Doxorubicin can be decreased when it is combined with Enzalutamide.
ErythromycinThe serum concentration of Doxorubicin can be increased when it is combined with Erythromycin.
FlibanserinThe serum concentration of Doxorubicin can be increased when it is combined with Flibanserin.
FluconazoleThe serum concentration of Doxorubicin can be increased when it is combined with Fluconazole.
FluoxetineThe serum concentration of Doxorubicin can be increased when it is combined with Fluoxetine.
FosamprenavirThe serum concentration of Doxorubicin can be increased when it is combined with Fosamprenavir.
FosaprepitantThe serum concentration of Doxorubicin can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Doxorubicin can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Doxorubicin can be increased when it is combined with Fusidic Acid.
HaloperidolThe serum concentration of Doxorubicin can be increased when it is combined with Haloperidol.
IbrutinibThe serum concentration of Doxorubicin can be increased when it is combined with Ibrutinib.
IdelalisibThe serum concentration of Doxorubicin can be increased when it is combined with Idelalisib.
ImatinibThe serum concentration of Doxorubicin can be increased when it is combined with Imatinib.
ImipramineThe serum concentration of Doxorubicin can be increased when it is combined with Imipramine.
IndinavirThe serum concentration of Doxorubicin can be increased when it is combined with Indinavir.
IsavuconazoniumThe serum concentration of Doxorubicin can be increased when it is combined with Isavuconazonium.
IsoniazidThe serum concentration of Doxorubicin can be increased when it is combined with Isoniazid.
ItraconazoleThe serum concentration of Doxorubicin can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Doxorubicin can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Doxorubicin can be increased when it is combined with Ketoconazole.
LapatinibThe serum concentration of Doxorubicin can be increased when it is combined with Lapatinib.
LedipasvirThe serum concentration of Doxorubicin can be increased when it is combined with Ledipasvir.
LeflunomideThe risk or severity of adverse effects can be increased when Doxorubicin is combined with Leflunomide.
LomitapideThe serum concentration of Doxorubicin can be increased when it is combined with Lomitapide.
LopinavirThe serum concentration of Doxorubicin can be increased when it is combined with Lopinavir.
LorcaserinThe serum concentration of Doxorubicin can be increased when it is combined with Lorcaserin.
LuliconazoleThe serum concentration of Doxorubicin can be increased when it is combined with Luliconazole.
LumefantrineThe serum concentration of Doxorubicin can be increased when it is combined with Lumefantrine.
MefloquineThe serum concentration of Doxorubicin can be increased when it is combined with Mefloquine.
MercaptopurineDoxorubicin may increase the hepatotoxic activities of Mercaptopurine.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Doxorubicin.
MethadoneThe serum concentration of Doxorubicin can be increased when it is combined with Methadone.
MethotrimeprazineThe serum concentration of Doxorubicin can be increased when it is combined with Methotrimeprazine.
MifepristoneThe serum concentration of Doxorubicin can be increased when it is combined with Mifepristone.
MirabegronThe serum concentration of Doxorubicin can be increased when it is combined with Mirabegron.
MitotaneThe serum concentration of Doxorubicin can be decreased when it is combined with Mitotane.
NatalizumabThe risk or severity of adverse effects can be increased when Doxorubicin is combined with Natalizumab.
NefazodoneThe serum concentration of Doxorubicin can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Doxorubicin can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Doxorubicin can be increased when it is combined with Netupitant.
NicardipineThe serum concentration of Doxorubicin can be increased when it is combined with Nicardipine.
NilotinibThe serum concentration of Doxorubicin can be increased when it is combined with Nilotinib.
PaclitaxelThe metabolism of Doxorubicin can be decreased when combined with Paclitaxel.
PalbociclibThe serum concentration of Doxorubicin can be increased when it is combined with Palbociclib.
PalonosetronThe serum concentration of Doxorubicin can be increased when it is combined with Palonosetron.
PanobinostatThe serum concentration of Doxorubicin can be increased when it is combined with Panobinostat.
ParoxetineThe serum concentration of Doxorubicin can be increased when it is combined with Paroxetine.
Peginterferon alfa-2bThe serum concentration of Doxorubicin can be decreased when it is combined with Peginterferon alfa-2b.
PhenobarbitalThe serum concentration of Doxorubicin can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Doxorubicin can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Doxorubicin.
PosaconazoleThe serum concentration of Doxorubicin can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Doxorubicin can be decreased when it is combined with Primidone.
ProgesteroneThe serum concentration of Doxorubicin can be increased when it is combined with Progesterone.
PromazineThe serum concentration of Doxorubicin can be increased when it is combined with Promazine.
PropranololThe serum concentration of Doxorubicin can be increased when it is combined with Propranolol.
QuinidineThe serum concentration of Doxorubicin can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Doxorubicin can be increased when it is combined with Quinine.
RanolazineThe serum concentration of Doxorubicin can be increased when it is combined with Ranolazine.
ReserpineThe serum concentration of Doxorubicin can be increased when it is combined with Reserpine.
RifabutinThe serum concentration of Doxorubicin can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Doxorubicin can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Doxorubicin can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Doxorubicin can be increased when it is combined with Ritonavir.
RoflumilastRoflumilast may increase the immunosuppressive activities of Doxorubicin.
RolapitantThe serum concentration of Doxorubicin can be increased when it is combined with Rolapitant.
SaquinavirThe serum concentration of Doxorubicin can be increased when it is combined with Saquinavir.
SertralineThe serum concentration of Doxorubicin can be increased when it is combined with Sertraline.
SiltuximabThe serum concentration of Doxorubicin can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Doxorubicin can be increased when it is combined with Simeprevir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Doxorubicin.
SofosbuvirThe serum concentration of Doxorubicin can be increased when it is combined with Sofosbuvir.
SorafenibThe serum concentration of Doxorubicin can be increased when it is combined with Sorafenib.
St. John's WortThe serum concentration of Doxorubicin can be decreased when it is combined with St. John&#39;s Wort.
StavudineThe therapeutic efficacy of Stavudine can be decreased when used in combination with Doxorubicin.
StiripentolThe serum concentration of Doxorubicin can be increased when it is combined with Stiripentol.
SulfisoxazoleThe serum concentration of Doxorubicin can be increased when it is combined with Sulfisoxazole.
SunitinibThe serum concentration of Doxorubicin can be increased when it is combined with Sunitinib.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Doxorubicin.
TamoxifenThe serum concentration of Doxorubicin can be increased when it is combined with Tamoxifen.
TelaprevirThe serum concentration of Doxorubicin can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Doxorubicin can be increased when it is combined with Telithromycin.
TerbinafineThe serum concentration of Doxorubicin can be increased when it is combined with Terbinafine.
TesmilifeneThe serum concentration of Doxorubicin can be decreased when it is combined with Tesmilifene.
ThioridazineThe serum concentration of Doxorubicin can be increased when it is combined with Thioridazine.
TiclopidineThe serum concentration of Doxorubicin can be increased when it is combined with Ticlopidine.
TipranavirThe serum concentration of Doxorubicin can be decreased when it is combined with Tipranavir.
TocilizumabThe serum concentration of Doxorubicin can be decreased when it is combined with Tocilizumab.
TofacitinibDoxorubicin may increase the immunosuppressive activities of Tofacitinib.
TranylcypromineThe serum concentration of Doxorubicin can be increased when it is combined with Tranylcypromine.
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Doxorubicin.
VandetanibThe serum concentration of Doxorubicin can be increased when it is combined with Vandetanib.
VemurafenibThe serum concentration of Doxorubicin can be increased when it is combined with Vemurafenib.
VerapamilThe serum concentration of Doxorubicin can be increased when it is combined with Verapamil.
VinblastineThe serum concentration of Doxorubicin can be decreased when it is combined with Vinblastine.
VoriconazoleThe serum concentration of Doxorubicin can be increased when it is combined with Voriconazole.
ZidovudineThe risk or severity of adverse effects can be increased when Doxorubicin is combined with Zidovudine.
Food Interactions
  • Liberal fluid intake to increase urine output and help the excretion of uric acid.

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. 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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
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 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. 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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compou...
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular Weight:
60845.33 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
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. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alp...
Gene Name:
CBR1
Uniprot ID:
P16152
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
Human
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
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
Human
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 glyceraldehyde to glycerol. Has broad substrate specificity. In vitro substrates include succinic semialdehyde, 4-nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D-glucuronic acid. Plays a role in the ac...
Gene Name:
AKR1A1
Uniprot ID:
P14550
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
Human
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. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms andro...
Gene Name:
AKR1C3
Uniprot ID:
P42330
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
Human
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 vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Gene Name:
NQO1
Uniprot ID:
P15559
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
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xanthine oxidase activity
Specific Function:
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:
XDH
Uniprot ID:
P47989
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
Human
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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
Gene Name:
NOS1
Uniprot ID:
P29475
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
Human
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 and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-n...
Gene Name:
NOS2
Uniprot ID:
P35228
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
Human
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)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by ...
Gene Name:
NOS3
Uniprot ID:
P29474
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
Human
Pharmacological action
unknown
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 transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity).
Gene Name:
NDUFS2
Uniprot ID:
O75306
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
Human
Pharmacological action
unknown
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 transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity).
Gene Name:
NDUFS3
Uniprot ID:
O75489
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
Human
Pharmacological action
unknown
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 transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity).
Gene Name:
NDUFS7
Uniprot ID:
O75251
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
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function:
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Gene Name:
POR
Uniprot ID:
P16435
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 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitorinducer
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
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
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
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
Human
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 hepatocytes (By similarity).
Gene Name:
ABCC3
Uniprot ID:
O15438
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
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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) and N-ethylmaleimide S-glutathione (NEM-GS).Isoform 2: Inhibits TNF-alpha-mediated apoptosis through blocking one or more caspases.
Gene Name:
ABCC6
Uniprot ID:
O95255
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
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
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
Human
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 involved in the maturation of spermatozoa. Also transports organic cations such as tetraethylammonium (TEA) and doxorubicin. The uptake of TEA is inhibited by various organic cations. The uptake of dox...
Gene Name:
SLC22A16
Uniprot ID:
Q86VW1
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
Human
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
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
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transporter activity
Specific Function:
Not Available
Gene Name:
ABCB8
Uniprot ID:
Q9NUT2
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
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transporter activity
Specific Function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name:
ABCB11
Uniprot ID:
O95342
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
Human
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 major ATP-dependent transporter of glutathione conjugates of electrophiles (GS-E) and DOX in erythrocytes. Can catalyze transport of glutathione conjugates and xenobiotics, and may contribute to the mul...
Gene Name:
RALBP1
Uniprot ID:
Q15311
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
Human
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
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 ]
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Drug created on June 13, 2005 07:24 / Updated on April 15, 2016 11:25