Identification

Name
Mitoxantrone
Accession Number
DB01204
Description

An anthracenedione-derived antineoplastic agent.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 444.4809
Monoisotopic: 444.200884648
Chemical Formula
C22H28N4O6
Synonyms
  • 1,4-Bis(2-(2-hydroxyethylamino)ethyl)amino)-5,8-dihydroxyanthraquinone
  • Mitoxantrona
  • Mitoxantrone
  • Mitoxantronum

Pharmacology

Indication

For the treatment of secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis

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

Mitoxantrone has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2.

Mechanism of action

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.

TargetActionsOrganism
ADNA
intercalation
Humans
ADNA topoisomerase 2-alpha
inhibitor
Humans
Absorption

Poorly absorbed following oral administration

Volume of distribution
  • 1000 L/m2
Protein binding

78%

Metabolism

Hepatic

Route of elimination
Not Available
Half-life

75 hours

Clearance
  • 21.3 L/hr/m2 [Elderly patients with breast cancer receiving IV administration of 15-90 mg/m2]
  • 28.3 L/hr/m2 [Non-elderly patients with nasopharyngeal carcinoma receiving IV administration of 15-90 mg/m2]
  • 16.2 L/hr/m2 [Non-elderly patients with malignant lymphoma receiving IV administration of 15-90 mg/m2]
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Severe leukopenia with infection.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Mitoxantrone is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Mitoxantrone.
AbemaciclibAbemaciclib may decrease the excretion rate of Mitoxantrone which could result in a higher serum level.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Mitoxantrone.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Mitoxantrone.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Mitoxantrone.
AcetaminophenAcetaminophen may increase the hepatotoxic activities of Mitoxantrone.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Mitoxantrone.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Mitoxantrone.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Mitoxantrone.
Additional Data Available
  • Extended Description
    Extended Description

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

    Learn more
  • Severity
    Severity

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

    Learn more
  • Evidence Level
    Evidence Level

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

    Learn more
  • Action
    Action

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

    Learn more
Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Mitoxantrone hydrochlorideU6USW86RD070476-82-3ZAHQPTJLOCWVPG-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Mitoxantrone InjectionSolutionIntravenousFresenius Kabi2007-12-03Not applicableCanada flag
Mitoxantrone InjectionSolutionIntravenousTEVA Canada Limited2006-03-282018-07-09Canada flag
Mitoxantrone Injection USPSolutionIntravenousPfizer Canada Ulc2001-12-032019-03-26Canada flag
NovantroneInjection, solution30 mg/15mLIntravenousSerono, Inc.2006-02-162006-08-21US flag
NovantroneLiquid2 mgIntravenousWyeth Ltd.1996-12-022005-08-10Canada flag
NovantroneInjection, solution25 mg/12.5mLIntravenousSerono, Inc.2006-02-162006-08-21US flag
NovantroneInjection, solution20 mg/10mLIntravenousEmd Serono1987-12-232011-06-08US flag
Novantrone Inj 2mg/mlLiquidIntravenousLederle Cyanamid Canada Inc.1984-12-311997-08-14Canada 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
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MitoxantroneInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals2006-04-112010-05-31US flag
MitoxantroneInjection, solution2 mg/1mLIntravenousFresenius Kabi USA, LLC2006-04-11Not applicableUS flag
mitoXANTRONEInjection, solution, concentrate2 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2006-04-11Not applicableUS flag
MitoxantroneInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals2006-04-112010-05-31US flag
mitoXANTRONEInjection, solution, concentrate2 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2006-04-11Not applicableUS flag
MitoxantroneInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals2006-04-112010-05-31US flag
MitoxantroneInjection, solution, concentrate2 mg/1mLIntravenousHospira, Inc.2006-04-11Not applicableUS flag
mitoXANTRONEInjection, solution, concentrate2 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2006-04-11Not applicableUS flag
Mitoxantrone HydrochlorideInjection, solution2 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc.2012-12-122016-12-31US 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

Categories

ATC Codes
L01DB07 — Mitoxantrone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as anthraquinones. These are organic compounds containing either anthracene-9,10-quinone, 1,4-anthraquinone, or 1,2-anthraquinone.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Anthracenes
Sub Class
Anthraquinones
Direct Parent
Anthraquinones
Alternative Parents
Aryl ketones / Secondary alkylarylamines / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous amides / Vinylogous acids / 1,2-aminoalcohols / Dialkylamines / Primary alcohols / Organopnictogen compounds / Organic oxides
show 1 more
Substituents
1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / 9,10-anthraquinone / Alcohol / Alkanolamine / Amine / Anthraquinone / Aromatic homopolycyclic compound / Aryl ketone / Hydrocarbon derivative
show 13 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
hydroxyanthraquinones (CHEBI:50729)

Chemical Identifiers

UNII
BZ114NVM5P
CAS number
65271-80-9
InChI Key
KKZJGLLVHKMTCM-UHFFFAOYSA-N
InChI
InChI=1S/C22H28N4O6/c27-11-9-23-5-7-25-13-1-2-14(26-8-6-24-10-12-28)18-17(13)21(31)19-15(29)3-4-16(30)20(19)22(18)32/h1-4,23-30H,5-12H2
IUPAC Name
1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)-9,10-dihydroanthracene-9,10-dione
SMILES
OCCNCCNC1=CC=C(NCCNCCO)C2=C1C(=O)C1=C(C(O)=CC=C1O)C2=O

References

Synthesis Reference
US4197249
General References
  1. Fox EJ: Management of worsening multiple sclerosis with mitoxantrone: a review. Clin Ther. 2006 Apr;28(4):461-74. [PubMed:16750460]
Human Metabolome Database
HMDB0015335
KEGG Drug
D08224
KEGG Compound
C11195
PubChem Compound
4212
PubChem Substance
46504608
ChemSpider
4067
BindingDB
67690
RxNav
7005
ChEBI
50729
ChEMBL
CHEMBL58
ZINC
ZINC000003794794
Therapeutic Targets Database
DAP000057
PharmGKB
PA450526
PDBe Ligand
MIX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mitoxantrone
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2fum / 2kgp / 4g0v / 4i41 / 6gh9 / 6vxi
FDA label
Download (1.3 MB)
MSDS
Download (53.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionAcute Myeloid Leukemia (AML)1
4CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)2
4CompletedTreatmentAcute Promyelocytic Leukemia (APL)1
4CompletedTreatmentAdult Acute Lymphocytic Leukemia1
4CompletedTreatmentAutoimmune Diseases of the Nervous System / Demyelinating Autoimmune Diseases, CNS / Myelitis transverse / Neuromyelitis Optica / Transverse Myelitis1
4CompletedTreatmentLeukemia, Nonlymphocytic, Acute1
4Enrolling by InvitationTreatmentChildhood Acute Promyelocytic Leukemia1
4Unknown StatusPreventionAcute Promyelocytic Leukemia (APL)1
4Unknown StatusTreatmentAcute Myeloid Leukemia (AML)1
4Unknown StatusTreatmentNeuromyelitis Optica / Neuromyelitis Optica Spectrum Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • EMD Canada Inc.
  • Hospira Inc.
  • Otn Generics Inc.
  • Pierre Fabre
  • Sicor Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Wyeth Pharmaceuticals
Dosage Forms
FormRouteStrength
SolutionIntravenous20 mg
Injection, solution, concentrateIntravenous10 mg/5ml
Injection, solution, concentrateIntravenous20 mg/10ml
Injection, solutionIntravenous2 mg/1mL
Injection, solution, concentrateIntravenous2 mg/1mL
Injection, solution, concentrateIntravenous; Parenteral2 MG/ML
Injection20 mg/10ml
Solution
SolutionIntravenous
Injection, solution, concentrateIntravenous2 MG/ML
InjectionIntravenous20 mg/10ml
Injection, solutionIntravenous20 mg/10mL
Injection, solutionIntravenous25 mg/12.5mL
Injection, solutionIntravenous30 mg/15mL
LiquidIntravenous2 mg
LiquidIntravenous
Injection, solution, concentrateIntravenous; Parenteral10 MG
Injection, solution, concentrateIntravenous; Parenteral20 MG
Injection, solution, concentrateIntravenous; Parenteral25 MG
Injection, solution, concentrateIntravenous; Parenteral30 MG
Prices
Unit descriptionCostUnit
Novantrone 2 mg/ml Concentrate 10ml Vial1649.32USD vial
Novantrone 2 mg/ml vial158.59USD ml
Mitoxantrone 20 mg/10 ml vial42.0USD ml
Mitoxantrone 25 mg/12.5 ml vial37.5USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
logP-3.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.734 mg/mLALOGPS
logP0.91ALOGPS
logP0.65ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)8.27ChemAxon
pKa (Strongest Basic)9.36ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area163.18 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity123.53 m3·mol-1ChemAxon
Polarizability48.49 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7557
Blood Brain Barrier-0.7979
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8417
P-glycoprotein inhibitor INon-inhibitor0.8674
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterNon-inhibitor0.7735
CYP450 2C9 substrateNon-substrate0.7907
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7013
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8544
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9211
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.8742
BiodegradationNot ready biodegradable0.9727
Rat acute toxicity2.3061 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5839
hERG inhibition (predictor II)Inhibitor0.6894
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/MSsplash10-0002-0012900000-147e3b4eed2bd9c29e51
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4j-0394000000-5f26812f41567533fe71

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. Mazerski J, Martelli S, Borowski E: The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations. Acta Biochim Pol. 1998;45(1):1-11. [PubMed:9701490]
  2. Hajihassan Z, Rabbani-Chadegani A: Studies on the binding affinity of anticancer drug mitoxantrone to chromatin, DNA and histone proteins. J Biomed Sci. 2009 Mar 11;16:31. doi: 10.1186/1423-0127-16-31. [PubMed:19284573]
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. Takeda K, Shinohara K, Kameda N, Ariyoshi K: A case of therapy-related acute myeloblastic leukemia with t(16;21)(q24;q22) after chemotherapy with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and the alkylating agent, cyclophosphamide. Int J Hematol. 1998 Feb;67(2):179-86. [PubMed:9631585]
  3. McPherson JP, Deffie AM, Jones NR, Brown GA, Deuchars KL, Goldenberg GJ: Selective sensitization of adriamycin-resistant P388 murine leukemia cells to antineoplastic agents following transfection with human DNA topoisomerase II alpha. Anticancer Res. 1997 Nov-Dec;17(6D):4243-52. [PubMed:9494516]
  4. Wang H, Mao Y, Zhou N, Hu T, Hsieh TS, Liu LF: Atp-bound topoisomerase ii as a target for antitumor drugs. J Biol Chem. 2001 May 11;276(19):15990-5. Epub 2001 Feb 23. [PubMed:11278845]
  5. Satherley K, de Souza L, Neale MH, Alexander RA, Myatt N, Foss AJ, Hungerford JL, Hickson ID, Cree IA: Relationship between expression of topoisomerase II isoforms and chemosensitivity in choroidal melanoma. J Pathol. 2000 Oct;192(2):174-81. [PubMed:11004693]
  6. Mao Y, Yu C, Hsieh TS, Nitiss JL, Liu AA, Wang H, Liu LF: Mutations of human topoisomerase II alpha affecting multidrug resistance and sensitivity. Biochemistry. 1999 Aug 17;38(33):10793-800. [PubMed:10451375]
  7. Ko MW, Tamhankar MA, Volpe NJ, Porter D, McGrath C, Galetta SL: Acute promyelocytic leukemic involvement of the optic nerves following mitoxantrone treatment for multiple sclerosis. J Neurol Sci. 2008 Oct 15;273(1-2):144-7. doi: 10.1016/j.jns.2008.06.028. Epub 2008 Aug 6. [PubMed:18687447]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. FDA Approved Drug Products: Mitoxantrone [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL: Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41. [PubMed:11160641]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
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. 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]

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. Schrenk D, Michalke A, Gant TW, Brown PC, Silverman JA, Thorgeirsson SS: Multidrug resistance gene expression in rodents and rodent hepatocytes treated with mitoxantrone. Biochem Pharmacol. 1996 Nov 8;52(9):1453-60. [PubMed:8937457]
  2. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674]
  3. Taipalensuu J, Tavelin S, Lazorova L, Svensson AC, Artursson P: Exploring the quantitative relationship between the level of MDR1 transcript, protein and function using digoxin as a marker of MDR1-dependent drug efflux activity. Eur J Pharm Sci. 2004 Jan;21(1):69-75. [PubMed:14706813]
  4. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. doi: 10.1111/j.1349-7006.2009.01213.x. Epub 2009 May 12. [PubMed:19493273]
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. Morrow CS, Peklak-Scott C, Bishwokarma B, Kute TE, Smitherman PK, Townsend AJ: Multidrug resistance protein 1 (MRP1, ABCC1) mediates resistance to mitoxantrone via glutathione-dependent drug efflux. Mol Pharmacol. 2006 Apr;69(4):1499-505. Epub 2006 Jan 24. [PubMed:16434618]
  2. Diah SK, Smitherman PK, Aldridge J, Volk EL, Schneider E, Townsend AJ, Morrow CS: Resistance to mitoxantrone in multidrug-resistant MCF7 breast cancer cells: evaluation of mitoxantrone transport and the role of multidrug resistance protein family proteins. Cancer Res. 2001 Jul 15;61(14):5461-7. [PubMed:11454692]
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. Volk EL, Schneider E: Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43. [PubMed:14500392]
  2. Elahian F, Kalalinia F, Behravan J: Evaluation of indomethacin and dexamethasone effects on BCRP-mediated drug resistance in MCF-7 parental and resistant cell lines. Drug Chem Toxicol. 2010 Apr;33(2):113-9. doi: 10.3109/01480540903390000. [PubMed:20307139]
  3. Morrow CS, Peklak-Scott C, Bishwokarma B, Kute TE, Smitherman PK, Townsend AJ: Multidrug resistance protein 1 (MRP1, ABCC1) mediates resistance to mitoxantrone via glutathione-dependent drug efflux. Mol Pharmacol. 2006 Apr;69(4):1499-505. Epub 2006 Jan 24. [PubMed:16434618]
  4. Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross DD, Miyake K, Resau JH, Bates SE: The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci. 2000 Jun;113 ( Pt 11):2011-21. [PubMed:10806112]
  5. 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]
  6. Sugimoto Y, Tsukahara S, Imai Y, Sugimoto Y, Ueda K, Tsuruo T: Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther. 2003 Jan;2(1):105-12. [PubMed:12533678]
  7. Maliepaard M, van Gastelen MA, de Jong LA, Pluim D, van Waardenburg RC, Ruevekamp-Helmers MC, Floot BG, Schellens JH: Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res. 1999 Sep 15;59(18):4559-63. [PubMed:10493507]
  8. 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]
  9. Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol. 2003 Sep;64(3):610-8. [PubMed:12920197]
  10. Miwa M, Tsukahara S, Ishikawa E, Asada S, Imai Y, Sugimoto Y: Single amino acid substitutions in the transmembrane domains of breast cancer resistance protein (BCRP) alter cross resistance patterns in transfectants. Int J Cancer. 2003 Dec 10;107(5):757-63. [PubMed:14566825]
  11. Nakanishi T, Doyle LA, Hassel B, Wei Y, Bauer KS, Wu S, Pumplin DW, Fang HB, Ross DD: Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis. Mol Pharmacol. 2003 Dec;64(6):1452-62. [PubMed:14645676]
  12. 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]
  13. Allen JD, Brinkhuis RF, Wijnholds J, Schinkel AH: The mouse Bcrp1/Mxr/Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res. 1999 Sep 1;59(17):4237-41. [PubMed:10485464]
  14. 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]
  15. Paturi DK, Kwatra D, Ananthula HK, Pal D, Mitra AK: Identification and functional characterization of breast cancer resistance protein in human bronchial epithelial cells (Calu-3). Int J Pharm. 2010 Jan 15;384(1-2):32-8. doi: 10.1016/j.ijpharm.2009.09.037. Epub 2009 Sep 25. [PubMed:19782742]
  16. Ma Y, Wink M: The beta-carboline alkaloid harmine inhibits BCRP and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells. Phytother Res. 2010 Jan;24(1):146-9. doi: 10.1002/ptr.2860. [PubMed:19548284]
  17. Mahringer A, Delzer J, Fricker G: A fluorescence-based in vitro assay for drug interactions with breast cancer resistance protein (BCRP, ABCG2). Eur J Pharm Biopharm. 2009 Aug;72(3):605-13. doi: 10.1016/j.ejpb.2009.01.010. [PubMed:19572416]
  18. Nicolle E, Boccard J, Guilet D, Dijoux-Franca MG, Zelefac F, Macalou S, Grosselin J, Schmidt J, Carrupt PA, Di Pietro A, Boumendjel A: Breast cancer resistance protein (BCRP/ABCG2): new inhibitors and QSAR studies by a 3D linear solvation energy approach. Eur J Pharm Sci. 2009 Aug 12;38(1):39-46. doi: 10.1016/j.ejps.2009.05.012. Epub 2009 Jun 6. [PubMed:19501160]
  19. Jani M, Szabo P, Kis E, Molnar E, Glavinas H, Krajcsi P: Kinetic characterization of sulfasalazine transport by human ATP-binding cassette G2. Biol Pharm Bull. 2009 Mar;32(3):497-9. [PubMed:19252303]
  20. Karla PK, Earla R, Boddu SH, Johnston TP, Pal D, Mitra A: Molecular expression and functional evidence of a drug efflux pump (BCRP) in human corneal epithelial cells. Curr Eye Res. 2009 Jan;34(1):1-9. doi: 10.1080/02713680802518251. [PubMed:19172464]
  21. 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]
  22. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. doi: 10.1111/j.1349-7006.2009.01213.x. Epub 2009 May 12. [PubMed:19493273]
  23. Shi Z, Parmar S, Peng XX, Shen T, Robey RW, Bates SE, Fu LW, Shao Y, Chen YM, Zang F, Chen ZS: The epidermal growth factor tyrosine kinase inhibitor AG1478 and erlotinib reverse ABCG2-mediated drug resistance. Oncol Rep. 2009 Feb;21(2):483-9. [PubMed:19148526]
  24. Ross DD, Yang W, Abruzzo LV, Dalton WS, Schneider E, Lage H, Dietel M, Greenberger L, Cole SP, Doyle LA: Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. J Natl Cancer Inst. 1999 Mar 3;91(5):429-33. [PubMed:10070941]
  25. Brangi M, Litman T, Ciotti M, Nishiyama K, Kohlhagen G, Takimoto C, Robey R, Pommier Y, Fojo T, Bates SE: Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res. 1999 Dec 1;59(23):5938-46. [PubMed:10606239]
  26. Rocchi E, Khodjakov A, Volk EL, Yang CH, Litman T, Bates SE, Schneider E: The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane. Biochem Biophys Res Commun. 2000 Apr 29;271(1):42-6. [PubMed:10777678]
  27. Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH, Schellens JH, Schinkel AH: Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst. 2000 Oct 18;92(20):1651-6. [PubMed:11036110]

Drug created on June 13, 2005 07:24 / Updated on October 26, 2020 22:40

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates