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Identification
NamePazopanib
Accession NumberDB06589
TypeSmall Molecule
GroupsApproved
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.

Structure
Thumb
Synonyms
GW 78603
GW786034
Pazopanibum
External Identifiers
  • GW-786034
  • GW786034
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Votrienttablet, film coated200 mg/1oralGlaxo Smith Kline Llc2009-10-19Not applicableUs
Votrienttablet200 mgoralNovartis Pharmaceuticals Canada Inc2010-08-13Not applicableCanada
Votrienttablet400 mgoralNovartis Pharmaceuticals Canada IncNot applicableNot applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Pazopanib Hydrochloride
Thumb
  • InChI Key: MQHIQUBXFFAOMK-UHFFFAOYSA-N
  • Monoisotopic Mass: 473.140071444
  • Average Mass: 473.979
DBSALT000135
Categories
UNII7RN5DR86CK
CAS number444731-52-6
WeightAverage: 437.518
Monoisotopic: 437.163393705
Chemical FormulaC21H23N7O2S
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassAmines
Sub ClassTertiary amines
Direct ParentAlkyldiarylamines
Alternative Parents
Substituents
  • Alkyldiarylamine
  • Benzenesulfonamide
  • Indazole
  • Benzopyrazole
  • Aminotoluene
  • Toluene
  • Aminopyrimidine
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Pyrazole
  • Azole
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Hydrocarbon derivative
  • Organosulfur compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationTreatment of advanced renal cell cancer and advanced soft tissue sarcoma (in patients previously treated with chemotherapy)
PharmacodynamicsPazopanib 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 actionPazopanib 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.
Related Articles
AbsorptionAbsorption 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 eliminationPrimarily 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 life35 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.

ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral200 mg
Tabletoral400 mg
Tablet, film coatedoral200 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7105530 No2003-10-192023-10-19Us
US7262203 No2001-12-192021-12-19Us
US8114885 No2001-12-192021-12-19Us
Properties
StateSolid
Experimental PropertiesNot 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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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 ]
External Links
ATC CodesL01XE11
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (593 KB)
MSDSDownload (70.4 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Pazopanib can be increased when it is combined with Abiraterone.
Aluminum hydroxideThe serum concentration of Pazopanib can be decreased when it is combined with Aluminum hydroxide.
AmiodaroneThe serum concentration of Pazopanib can be increased when it is combined with Amiodarone.
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Pazopanib.
AprepitantThe serum concentration of Pazopanib can be increased when it is combined with Aprepitant.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Pazopanib.
AtazanavirThe serum concentration of Pazopanib can be increased when it is combined with Atazanavir.
AtorvastatinThe serum concentration of Pazopanib can be increased when it is combined with Atorvastatin.
AzithromycinThe serum concentration of Pazopanib can be increased when it is combined with Azithromycin.
BexaroteneThe serum concentration of Pazopanib can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Pazopanib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Pazopanib can be decreased when it is combined with Bosentan.
Calcium carbonateThe serum concentration of Pazopanib can be decreased when it is combined with Calcium carbonate.
CarbamazepineThe serum concentration of Pazopanib can be decreased when it is combined with Carbamazepine.
CarvedilolThe serum concentration of Pazopanib can be increased when it is combined with Carvedilol.
CeritinibThe serum concentration of Pazopanib can be increased when it is combined with Ceritinib.
CimetidineThe serum concentration of Pazopanib can be decreased when it is combined with Cimetidine.
CitalopramPazopanib may increase the QTc-prolonging activities of Citalopram.
ClarithromycinThe serum concentration of Pazopanib can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Pazopanib can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Pazopanib can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Pazopanib can be increased when it is combined with Crizotinib.
CyclosporineThe serum concentration of Pazopanib can be increased when it is combined with Cyclosporine.
DabrafenibThe serum concentration of Pazopanib can be increased when it is combined with Dabrafenib.
DaclatasvirThe serum concentration of Pazopanib can be increased when it is combined with Daclatasvir.
DarunavirThe serum concentration of Pazopanib can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Pazopanib can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Pazopanib can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Pazopanib.
DipyridamoleThe serum concentration of Pazopanib can be increased when it is combined with Dipyridamole.
DofetilidePazopanib may increase the QTc-prolonging activities of Dofetilide.
DronedaroneThe serum concentration of Pazopanib can be increased when it is combined with Dronedarone.
EliglustatThe serum concentration of Pazopanib can be increased when it is combined with Eliglustat.
EltrombopagThe serum concentration of Pazopanib can be increased when it is combined with Eltrombopag.
EnzalutamideThe serum concentration of Pazopanib can be decreased when it is combined with Enzalutamide.
ErythromycinThe serum concentration of Pazopanib can be increased when it is combined with Erythromycin.
EsomeprazoleThe serum concentration of Pazopanib can be decreased when it is combined with Esomeprazole.
FamotidineThe serum concentration of Pazopanib can be decreased when it is combined with Famotidine.
FlibanserinThe serum concentration of Pazopanib can be increased when it is combined with Flibanserin.
FluconazoleThe metabolism of Pazopanib can be decreased when combined with Fluconazole.
FluvastatinFluvastatin may increase the hepatotoxic activities of Pazopanib.
FosaprepitantThe serum concentration of Pazopanib can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Pazopanib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Pazopanib can be increased when it is combined with Fusidic Acid.
GefitinibThe serum concentration of Pazopanib can be increased when it is combined with Gefitinib.
GoserelinGoserelin may increase the QTc-prolonging activities of Pazopanib.
HydrocodoneThe serum concentration of Hydrocodone can be increased when it is combined with Pazopanib.
IbrutinibThe serum concentration of Pazopanib can be increased when it is combined with Ibrutinib.
IdelalisibThe serum concentration of Pazopanib can be increased when it is combined with Idelalisib.
ImatinibThe serum concentration of Pazopanib can be increased when it is combined with Imatinib.
IndinavirThe serum concentration of Pazopanib can be increased when it is combined with Indinavir.
IrinotecanThe serum concentration of the active metabolites of Irinotecan can be increased when Irinotecan is used in combination with Pazopanib.
ItraconazoleThe serum concentration of Pazopanib can be increased when it is combined with Itraconazole.
IvabradineIvabradine may increase the QTc-prolonging activities of Pazopanib.
IvacaftorThe serum concentration of Pazopanib can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Pazopanib can be increased when it is combined with Ketoconazole.
LansoprazoleThe serum concentration of Pazopanib can be decreased when it is combined with Lansoprazole.
LapatinibLapatinib may increase the QTc-prolonging activities of Pazopanib.
LeflunomideThe risk or severity of adverse effects can be increased when Pazopanib is combined with Leflunomide.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Pazopanib.
LomitapideThe serum concentration of Pazopanib can be increased when it is combined with Lomitapide.
LovastatinLovastatin may increase the hepatotoxic activities of Pazopanib.
LuliconazoleThe serum concentration of Pazopanib can be increased when it is combined with Luliconazole.
Magnesium hydroxideThe serum concentration of Pazopanib can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Pazopanib can be decreased when it is combined with Magnesium oxide.
MefloquineThe serum concentration of Pazopanib can be increased when it is combined with Mefloquine.
MifepristoneMifepristone may increase the QTc-prolonging activities of Pazopanib.
MirabegronThe serum concentration of Pazopanib can be increased when it is combined with Mirabegron.
MitotaneThe serum concentration of Pazopanib can be decreased when it is combined with Mitotane.
NatalizumabThe risk or severity of adverse effects can be increased when Pazopanib is combined with Natalizumab.
NefazodoneThe serum concentration of Pazopanib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Pazopanib can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Pazopanib can be increased when it is combined with Netupitant.
NicardipineThe serum concentration of Pazopanib can be increased when it is combined with Nicardipine.
NilotinibThe serum concentration of Pazopanib can be increased when it is combined with Nilotinib.
NimodipineThe serum concentration of Nimodipine can be increased when it is combined with Pazopanib.
NizatidineThe serum concentration of Pazopanib can be decreased when it is combined with Nizatidine.
OctreotideOctreotide may increase the QTc-prolonging activities of Pazopanib.
OmeprazoleThe serum concentration of Pazopanib can be decreased when it is combined with Omeprazole.
PalbociclibThe serum concentration of Pazopanib can be increased when it is combined with Palbociclib.
PamidronateThe risk or severity of adverse effects can be increased when Pazopanib is combined with Pamidronate.
PantoprazoleThe serum concentration of Pazopanib can be increased when it is combined with Pantoprazole.
PhenobarbitalThe serum concentration of Pazopanib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Pazopanib can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Pazopanib.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Pazopanib.
PitavastatinPitavastatin may increase the hepatotoxic activities of Pazopanib.
PosaconazoleThe serum concentration of Pazopanib can be increased when it is combined with Posaconazole.
PravastatinPravastatin may increase the hepatotoxic activities of Pazopanib.
PrimidoneThe serum concentration of Pazopanib can be decreased when it is combined with Primidone.
ProgesteroneThe serum concentration of Pazopanib can be increased when it is combined with Progesterone.
PropranololThe serum concentration of Pazopanib can be increased when it is combined with Propranolol.
QuinidineThe serum concentration of Pazopanib can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Pazopanib can be increased when it is combined with Quinine.
RabeprazoleThe serum concentration of Pazopanib can be decreased when it is combined with Rabeprazole.
RanitidineThe serum concentration of Pazopanib can be decreased when it is combined with Ranitidine.
RanolazineThe serum concentration of Pazopanib can be increased when it is combined with Ranolazine.
ReserpineThe serum concentration of Pazopanib can be increased when it is combined with Reserpine.
RifabutinThe serum concentration of Pazopanib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Pazopanib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Pazopanib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Pazopanib can be increased when it is combined with Ritonavir.
RoflumilastRoflumilast may increase the immunosuppressive activities of Pazopanib.
RolapitantThe serum concentration of Pazopanib can be increased when it is combined with Rolapitant.
RosuvastatinRosuvastatin may increase the hepatotoxic activities of Pazopanib.
SaquinavirThe serum concentration of Pazopanib can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Pazopanib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Pazopanib can be increased when it is combined with Simeprevir.
SimvastatinSimvastatin may increase the hepatotoxic activities of Pazopanib.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Pazopanib.
Sodium bicarbonateThe serum concentration of Pazopanib can be decreased when it is combined with Sodium bicarbonate.
St. John's WortThe serum concentration of Pazopanib can be decreased when it is combined with St. John&#39;s Wort.
StiripentolThe serum concentration of Pazopanib can be increased when it is combined with Stiripentol.
SunitinibThe serum concentration of Pazopanib can be increased when it is combined with Sunitinib.
TacrolimusThe serum concentration of Pazopanib can be increased when it is combined with Tacrolimus.
TamoxifenThe serum concentration of Pazopanib can be increased when it is combined with Tamoxifen.
TelaprevirThe serum concentration of Pazopanib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Pazopanib can be increased when it is combined with Telithromycin.
TeriflunomideThe serum concentration of Pazopanib can be increased when it is combined with Teriflunomide.
TesmilifeneThe serum concentration of Pazopanib can be decreased when it is combined with Tesmilifene.
TocilizumabThe serum concentration of Pazopanib can be decreased when it is combined with Tocilizumab.
TofacitinibPazopanib may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Pazopanib.
VandetanibThe serum concentration of Pazopanib can be increased when it is combined with Vandetanib.
VemurafenibThe serum concentration of Pazopanib can be increased when it is combined with Vemurafenib.
VerapamilThe serum concentration of Pazopanib can be increased when it is combined with Verapamil.
VoriconazoleThe serum concentration of Pazopanib can be increased when it is combined with Voriconazole.
Food Interactions
  • Avoid drinking grapefruit juice as it is a CYP 3A4 inhibitor and will increase exposure of pazopanib
  • Bioavailability increases with food. Take pazopanib on empty stomach.

Targets

Kind
Protein
Organism
Human
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 survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation ...
Gene Name:
FLT1
Uniprot ID:
P17948
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
Human
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 embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domai...
Gene Name:
KDR
Uniprot ID:
P35968
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
Human
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 cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced pr...
Gene Name:
FLT4
Uniprot ID:
P35916
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
Human
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 chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for...
Gene Name:
PDGFRA
Uniprot ID:
P16234
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
Human
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 development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of peri...
Gene Name:
PDGFRB
Uniprot ID:
P09619
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
Human
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 maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1...
Gene Name:
KIT
Uniprot ID:
P10721
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
Human
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 essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineraliz...
Gene Name:
FGFR3
Uniprot ID:
P22607
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
Human
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-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR recepto...
Gene Name:
ITK
Uniprot ID:
Q08881
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
Human
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
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
Human
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
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
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. 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
Human
Pharmacological action
unknown
Actions
substrate
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. 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
Human
Pharmacological action
unknown
Actions
substrate
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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
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
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
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 ]

Transporters

Kind
Protein
Organism
Human
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
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
Human
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 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. 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
Human
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, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
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 ]
Kind
Protein
Organism
Human
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 IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naph...
Gene Name:
UGT1A1
Uniprot ID:
P22309
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 ]
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Drug created on March 19, 2008 10:38 / Updated on May 31, 2016 02:13