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Identification
NameVandetanib
Accession NumberDB05294
TypeSmall Molecule
GroupsApproved
DescriptionVandetanib is an oral once-daily kinase inhibitor of tumour angiogenesis and tumour cell proliferation with the potential for use in a broad range of tumour types. On April 6 2011, vandetanib was approved by the FDA to treat nonresectable, locally advanced, or metastatic medullary thyroid cancer in adult patients.
Structure
Thumb
Synonyms
4-BROMO-2-fluoro-N-[(4e)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4(1H)-ylidene]aniline
4-quinazolinamine, N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-
N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-4-quinazolinamine
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
Zactima
ZD 6474
ZD6474
External Identifiers
  • ZD-6474
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CaprelsaTablet300 mg/1OralAstra Zeneca Pharmaceuticals Lp2011-07-25Not applicableUs
CaprelsaTablet, film coated100 mgOralGenzyme Europe Bv2012-02-17Not applicableEu
CaprelsaTablet, film coated300 mgOralGenzyme Europe Bv2012-02-17Not applicableEu
CaprelsaTablet100 mgOralGenzyme Canada A Division Of Sanofi Aventis Canada Inc2012-02-23Not applicableCanada
CaprelsaTablet100 mg/1OralAstra Zeneca Pharmaceuticals Lp2011-07-25Not applicableUs
CaprelsaTablet300 mgOralGenzyme Canada A Division Of Sanofi Aventis Canada Inc2012-02-23Not applicableCanada
VandetanibTablet100 mg/1OralAstra Zeneca Pharmaceuticals Lp2011-04-212016-11-04Us
VandetanibTablet300 mg/1OralAstra Zeneca Pharmaceuticals Lp2011-04-212016-11-04Us
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Zactima AstraZeneca
Zictifa AstraZeneca
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIYO460OQ37K
CAS number443913-73-3
WeightAverage: 475.354
Monoisotopic: 474.106666884
Chemical FormulaC22H24BrFN4O2
InChI KeyUHTHHESEBZOYNR-UHFFFAOYSA-N
InChI
InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27)
IUPAC Name
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
SMILES
COC1=C(OCC2CCN(C)CC2)C=C2N=CN=C(NC3=C(F)C=C(Br)C=C3)C2=C1
Pharmacology
IndicationVandetanib is currently approved as an alternative to local therapies for both unresectable and disseminated disease. Because Vandetanib can prolong the Q-T interval, it is contraindicated for use in patients with serious cardiac complications such as congenital long QT syndrome and uncompensated heart failure.
Structured Indications
PharmacodynamicsMean IC50 of approximately 2.1 μg/mL.
Mechanism of actionZD-6474 is a potent and selective inhibitor of VEGFR (vascular endothelial growth factor receptor), EGFR (epidermal growth factor receptor) and RET (REarranged during Transfection) tyrosine kinases. VEGFR- and EGFR-dependent signalling are both clinically validated pathways in cancer, including non-small-cell lung cancer (NSCLC). RET activity is important in some types of thyroid cancer, and early data with vandetanib in medullary thyroid cancer has led to orphan-drug designation by the regulatory authorities in the USA and EU.
TargetKindPharmacological actionActionsOrganismUniProt ID
Vascular endothelial growth factor AProteinunknown
inhibitor
HumanP15692 details
Epidermal growth factor receptorProteinunknown
inhibitor
HumanP00533 details
Protein-tyrosine kinase 6Proteinunknown
inhibitor
HumanQ13882 details
Angiopoietin-1 receptorProteinunknown
inhibitor
HumanQ02763 details
Related Articles
AbsorptionSlow- peak plasma concentrations reached at a median 6 hours. On multiple dosing, Vandetanib accumulates about 8 fold with steady state reached after around 3 months.
Volume of distribution

Vd of about 7450 L.

Protein bindingProtein binding of about 90%.
Metabolism

Unchanged vandentanib and metabolites vandetanib N-oxide and N-desmethyl vandetanib were detected in plasma, urine and feces. N-desmethyl-vandetanib is primarily produced by CYP3A4, and vandetanib-N-oxide is primarily produced by flavin–containing monooxygenase enzymes FMO1 and FMO3.

SubstrateEnzymesProduct
Vandetanib
Not Available
N-desmethyl vandetanibDetails
Route of eliminationAbout 69% was recovered following 21 days after a single dose of vandentanib. 44% was found in feces and 25% in urine.
Half lifeMedian half life of 19 days.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vandetanib.Approved
AlfuzosinAlfuzosin may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
AmantadineAmantadine may increase the QTc-prolonging activities of Vandetanib.Approved
AmiodaroneAmiodarone may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
AmitriptylineAmitriptyline may increase the QTc-prolonging activities of Vandetanib.Approved
AmoxapineAmoxapine may increase the QTc-prolonging activities of Vandetanib.Approved
AnagrelideAnagrelide may increase the QTc-prolonging activities of Vandetanib.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Vandetanib.Investigational
ApomorphineApomorphine may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
AprepitantThe serum concentration of Vandetanib can be increased when it is combined with Aprepitant.Approved, Investigational
ArformoterolArformoterol may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
AripiprazoleAripiprazole may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
Arsenic trioxideArsenic trioxide may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
ArtemetherVandetanib may increase the QTc-prolonging activities of Artemether.Approved
AsenapineVandetanib may increase the QTc-prolonging activities of Asenapine.Approved
AtazanavirThe metabolism of Vandetanib can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineAtomoxetine may increase the QTc-prolonging activities of Vandetanib.Approved
AzithromycinAzithromycin may increase the QTc-prolonging activities of Vandetanib.Approved
BedaquilineBedaquiline may increase the QTc-prolonging activities of Vandetanib.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Vandetanib.Approved, Investigational
BexaroteneThe serum concentration of Vandetanib can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe metabolism of Vandetanib can be decreased when combined with Boceprevir.Approved
BortezomibBortezomib may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
BosentanThe serum concentration of Vandetanib can be decreased when it is combined with Bosentan.Approved, Investigational
BuserelinBuserelin may increase the QTc-prolonging activities of Vandetanib.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Vandetanib.Approved
CarbamazepineThe serum concentration of Vandetanib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Vandetanib can be increased when it is combined with Ceritinib.Approved
ChloroquineChloroquine may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
ChlorpromazineChlorpromazine may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
CiprofloxacinCiprofloxacin may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
CisaprideCisapride may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational, Withdrawn
CitalopramCitalopram may increase the QTc-prolonging activities of Vandetanib.Approved
ClarithromycinClarithromycin may increase the QTc-prolonging activities of Vandetanib.Approved
ClemastineThe metabolism of Vandetanib can be decreased when combined with Clemastine.Approved
ClomipramineClomipramine may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
ClotrimazoleThe metabolism of Vandetanib can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineClozapine may increase the QTc-prolonging activities of Vandetanib.Approved
CobicistatThe metabolism of Vandetanib can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Vandetanib can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibCrizotinib may increase the QTc-prolonging activities of Vandetanib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Vandetanib.Approved, Investigational
CyclosporineThe metabolism of Vandetanib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Vandetanib can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Vandetanib can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Vandetanib can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Vandetanib can be decreased when it is combined with Deferasirox.Approved, Investigational
DegarelixDegarelix may increase the QTc-prolonging activities of Vandetanib.Approved
DelavirdineThe metabolism of Vandetanib can be decreased when combined with Delavirdine.Approved
DesfluraneDesflurane may increase the QTc-prolonging activities of Vandetanib.Approved
DesipramineDesipramine may increase the QTc-prolonging activities of Vandetanib.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Vandetanib.Approved
DexamethasoneThe serum concentration of Vandetanib can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Vandetanib.Approved
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Vandetanib.Approved
DihydroergotamineThe metabolism of Vandetanib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Vandetanib can be decreased when combined with Diltiazem.Approved
DiphenhydramineDiphenhydramine may increase the QTc-prolonging activities of Vandetanib.Approved
DisopyramideDisopyramide may increase the QTc-prolonging activities of Vandetanib.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Vandetanib.Approved, Investigational
DofetilideDofetilide may increase the QTc-prolonging activities of Vandetanib.Approved
DolasetronDolasetron may increase the QTc-prolonging activities of Vandetanib.Approved
DomperidoneDomperidone may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational, Vet Approved
DoxepinDoxepin may increase the QTc-prolonging activities of Vandetanib.Approved
DoxycyclineThe metabolism of Vandetanib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneDronedarone may increase the QTc-prolonging activities of Vandetanib.Approved
DroperidolDroperidol may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
EfavirenzThe serum concentration of Vandetanib can be decreased when it is combined with Efavirenz.Approved, Investigational
EliglustatVandetanib may increase the QTc-prolonging activities of Eliglustat.Approved
EnzalutamideThe serum concentration of Vandetanib can be decreased when it is combined with Enzalutamide.Approved
EribulinEribulin may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
ErythromycinErythromycin may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
EscitalopramEscitalopram may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
Eslicarbazepine acetateThe serum concentration of Vandetanib can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Vandetanib can be decreased when it is combined with Etravirine.Approved
EzogabineEzogabine may increase the QTc-prolonging activities of Vandetanib.Approved
FamotidineFamotidine may increase the QTc-prolonging activities of Vandetanib.Approved
FelbamateFelbamate may increase the QTc-prolonging activities of Vandetanib.Approved
FingolimodFingolimod may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
FlecainideFlecainide may increase the QTc-prolonging activities of Vandetanib.Approved, Withdrawn
FluconazoleFluconazole may increase the QTc-prolonging activities of Vandetanib.Approved
FluoxetineFluoxetine may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
FlupentixolFlupentixol may increase the QTc-prolonging activities of Vandetanib.Approved, Withdrawn
FluvoxamineThe metabolism of Vandetanib can be decreased when combined with Fluvoxamine.Approved, Investigational
FormoterolFormoterol may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
FosamprenavirThe metabolism of Vandetanib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Vandetanib can be increased when it is combined with Fosaprepitant.Approved
FoscarnetFoscarnet may increase the QTc-prolonging activities of Vandetanib.Approved
FosphenytoinThe serum concentration of Vandetanib can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Vandetanib can be increased when it is combined with Fusidic Acid.Approved
Gadobenic acidGadobenic acid may increase the QTc-prolonging activities of Vandetanib.Approved
GalantamineGalantamine may increase the QTc-prolonging activities of Vandetanib.Approved
GemifloxacinGemifloxacin may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
GoserelinGoserelin may increase the QTc-prolonging activities of Vandetanib.Approved
GranisetronGranisetron may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
HaloperidolHaloperidol may increase the QTc-prolonging activities of Vandetanib.Approved
HistrelinHistrelin may increase the QTc-prolonging activities of Vandetanib.Approved
HydroxyzineHydroxyzine may increase the QTc-prolonging activities of Vandetanib.Approved
IbandronateIbandronate may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
IbutilideIbutilide may increase the QTc-prolonging activities of Vandetanib.Approved
IdelalisibThe serum concentration of Vandetanib can be increased when it is combined with Idelalisib.Approved
IloperidoneIloperidone may increase the QTc-prolonging activities of Vandetanib.Approved
ImatinibThe metabolism of Vandetanib can be decreased when combined with Imatinib.Approved
ImipramineImipramine may increase the QTc-prolonging activities of Vandetanib.Approved
IndacaterolIndacaterol may increase the QTc-prolonging activities of Vandetanib.Approved
IndapamideIndapamide may increase the QTc-prolonging activities of Vandetanib.Approved
IndinavirThe metabolism of Vandetanib can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Vandetanib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsofluraneIsoflurane may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
IsradipineIsradipine may increase the QTc-prolonging activities of Vandetanib.Approved
ItraconazoleThe metabolism of Vandetanib can be decreased when combined with Itraconazole.Approved, Investigational
IvabradineIvabradine may increase the QTc-prolonging activities of Vandetanib.Approved
IvacaftorThe serum concentration of Vandetanib can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Vandetanib can be decreased when combined with Ketoconazole.Approved, Investigational
LapatinibLapatinib may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
LenvatinibLenvatinib may increase the QTc-prolonging activities of Vandetanib.Approved
LeuprolideLeuprolide may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
LevofloxacinLevofloxacin may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
LithiumLithium may increase the QTc-prolonging activities of Vandetanib.Approved
LopinavirLopinavir may increase the QTc-prolonging activities of Vandetanib.Approved
LovastatinThe metabolism of Vandetanib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Vandetanib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Vandetanib can be decreased when it is combined with Lumacaftor.Approved
LumefantrineVandetanib may increase the QTc-prolonging activities of Lumefantrine.Approved
MaprotilineMaprotiline may increase the QTc-prolonging activities of Vandetanib.Approved
MefloquineMefloquine may increase the QTc-prolonging activities of Vandetanib.Approved
MetforminThe serum concentration of Metformin can be increased when it is combined with Vandetanib.Approved
MethadoneMethadone may increase the QTc-prolonging activities of Vandetanib.Approved
MethotrimeprazineMethotrimeprazine may increase the QTc-prolonging activities of Vandetanib.Approved
MetoclopramideMetoclopramide may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
MetronidazoleMetronidazole may increase the QTc-prolonging activities of Vandetanib.Approved
MifepristoneMifepristone may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
MirabegronMirabegron may increase the QTc-prolonging activities of Vandetanib.Approved
MirtazapineMirtazapine may increase the QTc-prolonging activities of Vandetanib.Approved
MitotaneThe serum concentration of Vandetanib can be decreased when it is combined with Mitotane.Approved
ModafinilThe serum concentration of Vandetanib can be decreased when it is combined with Modafinil.Approved, Investigational
MoexiprilMoexipril may increase the QTc-prolonging activities of Vandetanib.Approved
MoxifloxacinMoxifloxacin may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
NafcillinThe serum concentration of Vandetanib can be decreased when it is combined with Nafcillin.Approved
NefazodoneThe metabolism of Vandetanib can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Vandetanib can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Vandetanib can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Vandetanib can be decreased when it is combined with Nevirapine.Approved
NicardipineNicardipine may increase the QTc-prolonging activities of Vandetanib.Approved
NilotinibNilotinib may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
NorfloxacinNorfloxacin may increase the QTc-prolonging activities of Vandetanib.Approved
NortriptylineNortriptyline may increase the QTc-prolonging activities of Vandetanib.Approved
OctreotideOctreotide may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
OfloxacinOfloxacin may increase the QTc-prolonging activities of Vandetanib.Approved
OlanzapineOlanzapine may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
OlaparibThe metabolism of Vandetanib can be decreased when combined with Olaparib.Approved
OlodaterolOlodaterol may increase the QTc-prolonging activities of Vandetanib.Approved
OndansetronOndansetron may increase the QTc-prolonging activities of Vandetanib.Approved
OsimertinibThe serum concentration of Vandetanib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Vandetanib.Approved
OxytocinOxytocin may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Vandetanib.Approved, Vet Approved
PalbociclibThe serum concentration of Vandetanib can be increased when it is combined with Palbociclib.Approved
PaliperidonePaliperidone may increase the QTc-prolonging activities of Vandetanib.Approved
PanobinostatPanobinostat may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
ParoxetineParoxetine may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
PasireotidePasireotide may increase the QTc-prolonging activities of Vandetanib.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Vandetanib.Approved
PentamidinePentamidine may increase the QTc-prolonging activities of Vandetanib.Approved
PentobarbitalThe serum concentration of Vandetanib can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PerflutrenPerflutren may increase the QTc-prolonging activities of Vandetanib.Approved
PhenobarbitalThe serum concentration of Vandetanib can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Vandetanib can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimozidePimozide may increase the QTc-prolonging activities of Vandetanib.Approved
PosaconazoleThe metabolism of Vandetanib can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimaquinePrimaquine may increase the QTc-prolonging activities of Vandetanib.Approved
PrimidoneThe serum concentration of Vandetanib can be decreased when it is combined with Primidone.Approved, Vet Approved
ProcainamideProcainamide may increase the QTc-prolonging activities of Vandetanib.Approved
PromazinePromazine may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
PromethazinePromethazine may increase the QTc-prolonging activities of Vandetanib.Approved
PropafenonePropafenone may increase the QTc-prolonging activities of Vandetanib.Approved
PropofolPropofol may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational, Vet Approved
ProtriptylineProtriptyline may increase the QTc-prolonging activities of Vandetanib.Approved
QuetiapineQuetiapine may increase the QTc-prolonging activities of Vandetanib.Approved
QuinidineQuinidine may increase the QTc-prolonging activities of Vandetanib.Approved
QuinineQuinine may increase the QTc-prolonging activities of Vandetanib.Approved
RanolazineRanolazine may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
RifabutinThe serum concentration of Vandetanib can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Vandetanib can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Vandetanib can be decreased when it is combined with Rifapentine.Approved
RilpivirineRilpivirine may increase the QTc-prolonging activities of Vandetanib.Approved
RisperidoneRisperidone may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
RitonavirThe metabolism of Vandetanib can be decreased when combined with Ritonavir.Approved, Investigational
SalbutamolSalbutamol may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
SalmeterolSalmeterol may increase the QTc-prolonging activities of Vandetanib.Approved
SaquinavirSaquinavir may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
SertralineSertraline may increase the QTc-prolonging activities of Vandetanib.Approved
SevofluraneSevoflurane may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
SildenafilThe metabolism of Vandetanib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Vandetanib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Vandetanib can be increased when it is combined with Simeprevir.Approved
SolifenacinSolifenacin may increase the QTc-prolonging activities of Vandetanib.Approved
SorafenibSorafenib may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
SotalolSotalol may increase the QTc-prolonging activities of Vandetanib.Approved
St. John's WortThe serum concentration of Vandetanib can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Vandetanib can be increased when it is combined with Stiripentol.Approved
SulfamethoxazoleSulfamethoxazole may increase the QTc-prolonging activities of Vandetanib.Approved
SulfisoxazoleSulfisoxazole may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
SunitinibSunitinib may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
TamoxifenTamoxifen may increase the QTc-prolonging activities of Vandetanib.Approved
TelaprevirThe metabolism of Vandetanib can be decreased when combined with Telaprevir.Approved
TelavancinTelavancin may increase the QTc-prolonging activities of Vandetanib.Approved
TelithromycinTelithromycin may increase the QTc-prolonging activities of Vandetanib.Approved
TerbutalineTerbutaline may increase the QTc-prolonging activities of Vandetanib.Approved
TetrabenazineTetrabenazine may increase the QTc-prolonging activities of Vandetanib.Approved
ThioridazineThioridazine may increase the QTc-prolonging activities of Vandetanib.Approved
ThiothixeneThiothixene may increase the QTc-prolonging activities of Vandetanib.Approved
TiclopidineThe metabolism of Vandetanib can be decreased when combined with Ticlopidine.Approved
TizanidineTizanidine may increase the QTc-prolonging activities of Vandetanib.Approved
TocilizumabThe serum concentration of Vandetanib can be decreased when it is combined with Tocilizumab.Approved
TolterodineTolterodine may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Vandetanib.Approved, Investigational
ToremifeneToremifene may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Vandetanib.Approved, Investigational
TrazodoneTrazodone may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
TreprostinilTreprostinil may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
TrimethoprimTrimethoprim may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
TrimipramineTrimipramine may increase the QTc-prolonging activities of Vandetanib.Approved
TriptorelinTriptorelin may increase the QTc-prolonging activities of Vandetanib.Approved, Vet Approved
VardenafilVardenafil may increase the QTc-prolonging activities of Vandetanib.Approved
VemurafenibVandetanib may increase the QTc-prolonging activities of Vemurafenib.Approved
VenlafaxineVenlafaxine may increase the QTc-prolonging activities of Vandetanib.Approved
VerapamilThe metabolism of Vandetanib can be decreased when combined with Verapamil.Approved
VilanterolVilanterol may increase the QTc-prolonging activities of Vandetanib.Approved
VoriconazoleThe metabolism of Vandetanib can be decreased when combined with Voriconazole.Approved, Investigational
VorinostatVorinostat may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
ZiprasidoneZiprasidone may increase the QTc-prolonging activities of Vandetanib.Approved
ZuclopenthixolZuclopenthixol may increase the QTc-prolonging activities of Vandetanib.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Bates D: ZD-6474. AstraZeneca. Curr Opin Investig Drugs. 2003 Dec;4(12):1468-72. [PubMed:14763134 ]
  2. Ton GN, Banaszynski ME, Kolesar JM: Vandetanib: a novel targeted therapy for the treatment of metastatic or locally advanced medullary thyroid cancer. Am J Health Syst Pharm. 2013 May 15;70(10):849-55. doi: 10.2146/ajhp120253. [PubMed:23640345 ]
  3. Andriamanana I, Gana I, Duretz B, Hulin A: Simultaneous analysis of anticancer agents bortezomib, imatinib, nilotinib, dasatinib, erlotinib, lapatinib, sorafenib, sunitinib and vandetanib in human plasma using LC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 May 1;926:83-91. doi: 10.1016/j.jchromb.2013.01.037. Epub 2013 Mar 16. [PubMed:23562906 ]
External Links
ATC CodesL01XE12
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (220 KB)
MSDSDownload (220 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9961
Blood Brain Barrier+0.9596
Caco-2 permeable+0.611
P-glycoprotein substrateSubstrate0.7412
P-glycoprotein inhibitor IInhibitor0.7327
P-glycoprotein inhibitor IIInhibitor0.9501
Renal organic cation transporterInhibitor0.6556
CYP450 2C9 substrateNon-substrate0.8419
CYP450 2D6 substrateNon-substrate0.5827
CYP450 3A4 substrateSubstrate0.6006
CYP450 1A2 substrateInhibitor0.7333
CYP450 2C9 inhibitorNon-inhibitor0.7749
CYP450 2D6 inhibitorInhibitor0.5867
CYP450 2C19 inhibitorInhibitor0.5077
CYP450 3A4 inhibitorInhibitor0.5288
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8009
Ames testAMES toxic0.5693
CarcinogenicityNon-carcinogens0.9322
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5482 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Inhibitor0.8342
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral300 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral300 mg
TabletOral100 mg/1
TabletOral300 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7173038 No2001-08-142021-08-14Us
US8067427 No2008-08-082028-08-08Us
US8642608 No2002-02-062022-02-06Us
USRE42353 No1997-09-232017-09-23Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility0.008 mg/mL at 25°C (77°F )FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.0102 mg/mLALOGPS
logP5.01ALOGPS
logP4.54ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)13.8ChemAxon
pKa (Strongest Basic)9.13ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.51 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity118.63 m3·mol-1ChemAxon
Polarizability47.1 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (103 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassQuinazolines
Direct ParentQuinazolinamines
Alternative Parents
Substituents
  • Quinazolinamine
  • Anisole
  • Halobenzene
  • Fluorobenzene
  • Bromobenzene
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Piperidine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Aryl bromide
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Secondary amine
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organobromide
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Vascular endothelial growth factor receptor binding
Specific Function:
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activ...
Gene Name:
VEGFA
Uniprot ID:
P15692
Molecular Weight:
27042.205 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Ubiquitin protein ligase binding
Specific Function:
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on ke...
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular Weight:
134276.185 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Receptor binding
Specific Function:
Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These...
Gene Name:
PTK6
Uniprot ID:
Q13882
Molecular Weight:
51833.72 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from ...
Gene Name:
TEK
Uniprot ID:
Q02763
Molecular Weight:
125829.005 Da
References
  1. Link [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Nadp binding
Specific Function:
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name:
FMO1
Uniprot ID:
Q01740
Molecular Weight:
60310.285 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Trimethylamine monooxygenase activity
Specific Function:
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds (PubMed:9224773).
Gene Name:
FMO3
Uniprot ID:
P31513
Molecular Weight:
60032.975 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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. Link [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Link [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
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, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
References
  1. Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [PubMed:19390592 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
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. Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [PubMed:19390592 ]
Comments
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Drug created on November 18, 2007 11:23 / Updated on December 09, 2016 02:39