Identification

Name
Pazopanib
Accession Number
DB06589
Description

Pazopanib is a small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. It is developed by GlaxoSmithKline and was FDA approved on October 19, 2009.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 437.518
Monoisotopic: 437.163393705
Chemical Formula
C21H23N7O2S
Synonyms
  • Pazopanib
  • Pazopanibum
External IDs
  • GW 78603
  • GW-786034
  • GW786034

Pharmacology

Indication

Treatment of advanced renal cell cancer and advanced soft tissue sarcoma (in patients previously treated with chemotherapy)

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

Pazopanib is a synthetic indazolylpyrimidine and reaches steady state concentrations of >15 μg/ml. This concentration is high enough to observe maximal inhibition of VEGFR2 phosphorylation and some anti-tumour activity (concentration required to inhibit receptors is 0.01 - 0.084 μmol/L). A reduction in tumour blood flow, increased tumour apoptosis, inhibition of tumour growth, reduction in tumour interstitial fluid pressure, and hypoxia in cancer cells can be observed in patients receiving treatment.

Mechanism of action

Pazopanib is a second-generation multitargeted tyrosine kinase inhibitor against vascular endothelial growth factor receptor-1, -2, and -3, platelet-derived growth factor receptor-alpha, platelet-derived growth factor receptor-beta, and c-kit. These receptor targets are part of the angiogenesis pathway that facilitates the formation of tumour blood vessel for tumour survival and growth.

TargetActionsOrganism
AVascular endothelial growth factor receptor 1
inhibitor
Humans
AVascular endothelial growth factor receptor 2
inhibitor
Humans
AVascular endothelial growth factor receptor 3Not AvailableHumans
APlatelet-derived growth factor receptor alpha
inhibitor
Humans
APlatelet-derived growth factor receptor beta
inhibitor
Humans
AMast/stem cell growth factor receptor Kit
inhibitor
Humans
UFibroblast growth factor receptor 3
inhibitor
Humans
UTyrosine-protein kinase ITK/TSK
inhibitor
Humans
UFibroblast growth factor 1
inhibitor
Humans
USH2B adapter protein 3
inhibitor
Humans
Absorption

Absorption of pazopanib in cancer patients is slow and incomplete. In patients with solid tumour, over a dose range of 50-2000 mg, absorption is nonlinear. Significant accumulation of pazopanib can also be observed in patients receiving 800 mg once daily for 22 days. Crushing tablets may increase exposure (increase in Cmax and AUC, while Tmax decreases by 2 hours). Bioavailability, oral tablet 800 mg, cancer patient = 21%; Bioavailability may be low due to incomplete absorption from the gastrointestinal tract. The major circulating component of the drug in the systemic is pazopanib, and not its metabolites. Mean maximum plasma concentration= 58.1 µg/mL; Mean AUC= 1037 µg · h/mL;

Volume of distribution

Vd steady state, IV administration 5 mg, cancer patient = 11.1 L (range of 9.15 - 13.4)

Protein binding

>99% protein bound, independent of concentrations over a range of 10-100 μg/mL.

Metabolism

Metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C8. Metabolites are less active than pazopanib (10 to 20-fold less active). Three of its metabolites can be observed in the systemic and account for <10% of plasma radioactivity.

Route of elimination

Primarily excreted via feces (82.2%) and to a negligible extent via urine (<4%) in cancer patients. Most of the administered dose is excreted unchanged. Approximately 10% of dose are oxidative metabolites and are mostly eliminated via the feces.

Half-life

35 hours. Oral absorption is not the rate limiting step of elimination from the plasma.

Clearance

CL, cancer patient, IV administration 5 mg = 4mL/min Half of the absorbed dose is cleared via oxidative metabolism.

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
UDP-glucuronosyltransferase 1-1UGT1A1*28(TA;TA)TA pair insertionADR Directly StudiedThe presence of this polymorphism in UGT1A1 is associated with an increase in the incidence of hyperbilirubinemia when treated with pazopanib.Details
HLA class I histocompatibility antigen protein P5HLA-B*57:01(G;G)G alleleADR Directly StudiedThe presence of this polymorphism in HCP5 may indicate an increased risk of ALT elevation leading to drug-related hepatotoxicty from pazpanib therapy.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe metabolism of Abacavir can be decreased when combined with Pazopanib.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Pazopanib.
AbametapirThe serum concentration of Pazopanib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Pazopanib can be increased when combined with Abatacept.
AbemaciclibAbemaciclib may decrease the excretion rate of Pazopanib which could result in a higher serum level.
AbirateroneThe serum concentration of Pazopanib can be increased when it is combined with Abiraterone.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Pazopanib.
AcebutololThe risk or severity of QTc prolongation can be increased when Acebutolol is combined with Pazopanib.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Pazopanib.
AcetaminophenThe metabolism of Pazopanib can be increased when combined with Acetaminophen.
Additional Data Available
  • Extended Description
    Extended Description

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

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  • Severity
    Severity

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

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  • Evidence Level
    Evidence Level

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

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  • Action
    Action

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

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Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of pazopanib.
  • Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of pazopanib.
  • Take on an empty stomach. Separate pazopanib from meals by at least 1 hour before and 2 hours after eating as food increases pazopanib bioavailability.
  • Take separate from antacids. Separate the administration of pazopanib and antacids by several hours.

Products

Product Ingredients
IngredientUNIICASInChI Key
Pazopanib hydrochloride33Y9ANM545635702-64-6MQHIQUBXFFAOMK-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VotrientTablet, film coated400 mgOralNovartis Europharm Limited2010-06-14Not applicableEU flag
VotrientTablet200 mgOralNovartis2010-08-13Not applicableCanada flag
VotrientTablet, film coated200 mg/1OralGlaxosmithkline Inc2009-10-192017-11-30US flag
VotrientTablet, film coated200 mgOralNovartis Europharm Limited2010-06-14Not applicableEU flag
VotrientTablet400 mgOralNovartisNot applicableNot applicableCanada flag
VotrientTablet, film coated400 mgOralNovartis Europharm Limited2010-06-14Not applicableEU flag
VotrientTablet, film coated200 mgOralNovartis Europharm Limited2010-06-14Not applicableEU flag
VotrientTablet, film coated200 mg/1OralNovartis Pharmaceuticals Corporation2016-07-12Not applicableUS 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.

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  • Product Code
    Product Code

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

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Categories

ATC Codes
L01XE11 — Pazopanib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alkyldiarylamines. These are tertiary alkylarylamines having two aryl and one alkyl groups attached to the amino group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Alkyldiarylamines
Alternative Parents
Benzenesulfonamides / Benzenesulfonyl compounds / Indazoles / Aniline and substituted anilines / Toluenes / Aminopyrimidines and derivatives / Organosulfonamides / Imidolactams / Heteroaromatic compounds / Pyrazoles
show 6 more
Substituents
Alkyldiarylamine / Aminopyrimidine / Aminosulfonyl compound / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenesulfonamide / Benzenesulfonyl group / Benzenoid
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aminopyrimidine, sulfonamide, indazoles (CHEBI:71219)

Chemical Identifiers

UNII
7RN5DR86CK
CAS number
444731-52-6
InChI Key
CUIHSIWYWATEQL-UHFFFAOYSA-N
InChI
InChI=1S/C21H23N7O2S/c1-13-5-6-15(11-19(13)31(22,29)30)24-21-23-10-9-20(25-21)27(3)16-7-8-17-14(2)28(4)26-18(17)12-16/h5-12H,1-4H3,(H2,22,29,30)(H,23,24,25)
IUPAC Name
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide
SMILES
CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1

References

General References
  1. Sonpavde G, Hutson TE, Sternberg CN: Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert Opin Investig Drugs. 2008 Feb;17(2):253-61. doi: 10.1517/13543784.17.2.253. [PubMed:18230058]
  2. Verweij J, Sleijfer S: Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35. doi: 10.1517/14656566.2013.780030. Epub 2013 Mar 14. [PubMed:23488774]
  3. Deng Y, Sychterz C, Suttle AB, Dar MM, Bershas D, Negash K, Qian Y, Chen EP, Gorycki PD, Ho MY: Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53. doi: 10.3109/00498254.2012.734642. Epub 2012 Nov 16. [PubMed:23548165]
  4. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
KEGG Drug
D05380
PubChem Compound
10113978
PubChem Substance
175427074
ChemSpider
8289501
BindingDB
26474
RxNav
714438
ChEBI
71219
ChEMBL
CHEMBL477772
ZINC
ZINC000011617039
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pazopanib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (593 KB)
MSDS
Download (70.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingBasic ScienceClear-cell Metastatic Renal Cell Carcinoma1
4Active Not RecruitingOtherMetastatic Renal Cell Cancer1
4CompletedTreatmentClear-cell Metastatic Renal Cell Carcinoma / Locally Advanced and/or Metastatic Renal Cell Carcinoma / Renal Cell Adenocarcinoma1
4CompletedTreatmentMalignancies1
4RecruitingTreatmentSoft Tissue Sarcoma Adult1
3Active Not RecruitingTreatmentClear Cell Renal Cell Carcinoma / Stage IV Renal Cell Cancer AJCC V71
3Active Not RecruitingTreatmentRenal Cell Adenocarcinoma3
3CompletedTreatmentAdvanced Angiosarcoma1
3CompletedTreatmentMalignancies1
3CompletedTreatmentMetastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral200 mg
TabletOral400 mg
Tablet, film coatedOral
Tablet, film coatedOral200 mg
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral400 mg
Tablet, coated200 mg
Tablet, coated400 mg
Tablet
Tablet, coatedOral200 mg
Tablet, coatedOral400 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7262203No2007-08-282021-12-19US flag
US8114885No2012-02-142021-12-19US flag
US7105530No2006-09-122023-10-19US flag
Additional Data Available
  • Filed On
    Filed On

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

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0433 mg/mLALOGPS
logP3.59ALOGPS
logP3.55ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)10.41ChemAxon
pKa (Strongest Basic)5.07ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area119.03 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity132.18 m3·mol-1ChemAxon
Polarizability45.41 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8788
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.8307
P-glycoprotein inhibitor INon-inhibitor0.8126
P-glycoprotein inhibitor IIInhibitor0.5
Renal organic cation transporterNon-inhibitor0.8152
CYP450 2C9 substrateNon-substrate0.7797
CYP450 2D6 substrateNon-substrate0.8008
CYP450 3A4 substrateNon-substrate0.6024
CYP450 1A2 substrateNon-inhibitor0.5
CYP450 2C9 inhibitorNon-inhibitor0.5065
CYP450 2D6 inhibitorNon-inhibitor0.7779
CYP450 2C19 inhibitorNon-inhibitor0.6811
CYP450 3A4 inhibitorNon-inhibitor0.5385
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5668
Ames testNon AMES toxic0.6543
CarcinogenicityNon-carcinogens0.8567
BiodegradationNot ready biodegradable0.9935
Rat acute toxicity2.3961 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9219
hERG inhibition (predictor II)Non-inhibitor0.7129
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 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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-052r-0118900000-097bcfa914e959e3d51a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0910000000-fd84ad14c383d8fa623f

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Sonpavde G, Hutson TE: Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep. 2007 Mar;9(2):115-9. [PubMed:17288876]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an...
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Non-membrane spanning protein tyrosine kinase activity
Specific Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-c...
Gene Name
ITK
Uniprot ID
Q08881
Uniprot Name
Tyrosine-protein kinase ITK/TSK
Molecular Weight
71830.405 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
S100 protein binding
Specific Function
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
Gene Name
FGF1
Uniprot ID
P05230
Uniprot Name
Fibroblast growth factor 1
Molecular Weight
17459.58 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Signaling adaptor activity
Specific Function
Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.
Gene Name
SH2B3
Uniprot ID
Q9UQQ2
Uniprot Name
SH2B adapter protein 3
Molecular Weight
63224.45 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Keisner SV, Shah SR: Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54. doi: 10.2165/11588960-000000000-00000. [PubMed:21395357]
  2. Goh BC, Reddy NJ, Dandamudi UB, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD: An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors. Clin Pharmacol Ther. 2010 Nov;88(5):652-9. doi: 10.1038/clpt.2010.158. Epub 2010 Sep 29. [PubMed:20881954]
  3. Verweij J, Sleijfer S: Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35. doi: 10.1517/14656566.2013.780030. Epub 2013 Mar 14. [PubMed:23488774]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Keisner SV, Shah SR: Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54. doi: 10.2165/11588960-000000000-00000. [PubMed:21395357]
  2. Goh BC, Reddy NJ, Dandamudi UB, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD: An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors. Clin Pharmacol Ther. 2010 Nov;88(5):652-9. doi: 10.1038/clpt.2010.158. Epub 2010 Sep 29. [PubMed:20881954]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Keisner SV, Shah SR: Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54. doi: 10.2165/11588960-000000000-00000. [PubMed:21395357]
  2. Verweij J, Sleijfer S: Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35. doi: 10.1517/14656566.2013.780030. Epub 2013 Mar 14. [PubMed:23488774]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Verweij J, Sleijfer S: Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35. doi: 10.1517/14656566.2013.780030. Epub 2013 Mar 14. [PubMed:23488774]
  2. FDA Label, Pazopanib [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Deng Y, Sychterz C, Suttle AB, Dar MM, Bershas D, Negash K, Qian Y, Chen EP, Gorycki PD, Ho MY: Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53. doi: 10.3109/00498254.2012.734642. Epub 2012 Nov 16. [PubMed:23548165]
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. Deng Y, Sychterz C, Suttle AB, Dar MM, Bershas D, Negash K, Qian Y, Chen EP, Gorycki PD, Ho MY: Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53. doi: 10.3109/00498254.2012.734642. Epub 2012 Nov 16. [PubMed:23548165]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]
  2. Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A: Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations. Br J Cancer. 2014 Feb 18;110(4):894-8. doi: 10.1038/bjc.2013.811. Epub 2014 Jan 7. [PubMed:24398510]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Deeks ED: Pazopanib: in advanced soft tissue sarcoma. Drugs. 2012 Nov 12;72(16):2129-40. doi: 10.2165/11209950-000000000-00000. [PubMed:23072642]

Drug created on March 19, 2008 10:38 / Updated on October 27, 2020 11:13

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