Identification

Name
Vandetanib
Accession Number
DB05294  (DB08764)
Type
Small Molecule
Groups
Approved
Description

Vandetanib 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
  • 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
External IDs
GNF-PF-2188 / HSDB 8198 / ZD 6474 / ZD-6474 / ZD6474
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CaprelsaTablet100 mg/1OralAstra Zeneca Lp2011-07-25Not applicableUs
CaprelsaTablet300 mgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2012-02-23Not applicableCanada
CaprelsaTablet, film coated100 mgOralGenzyme Europe Bv2012-02-17Not applicableEu
CaprelsaTablet300 mg/1OralGenzyme Corporation2011-07-25Not applicableUs
CaprelsaTablet100 mgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2012-02-23Not applicableCanada
CaprelsaTablet300 mg/1OralAstra Zeneca Lp2011-07-25Not applicableUs
CaprelsaTablet100 mg/1OralGenzyme Corporation2011-07-25Not applicableUs
CaprelsaTablet, film coated300 mgOralGenzyme Europe Bv2012-02-17Not applicableEu
VandetanibTablet100 mg/1OralAstra Zeneca Lp2011-04-212016-11-04Us
VandetanibTablet300 mg/1OralAstra Zeneca Lp2011-04-212016-11-04Us
International/Other Brands
Zactima (AstraZeneca ) / Zictifa (AstraZeneca )
Categories
UNII
YO460OQ37K
CAS number
443913-73-3
Weight
Average: 475.354
Monoisotopic: 474.106666884
Chemical Formula
C22H24BrFN4O2
InChI Key
UHTHHESEBZOYNR-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

Indication

Vandetanib 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
Pharmacodynamics

Mean IC50 of approximately 2.1 μg/mL.

Mechanism of action

ZD-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.

TargetActionsOrganism
UVascular endothelial growth factor A
inhibitor
Human
UEpidermal growth factor receptor
inhibitor
Human
UProtein-tyrosine kinase 6
inhibitor
Human
UAngiopoietin-1 receptor
inhibitor
Human
UProto-oncogene tyrosine-protein kinase receptor RetNot AvailableHuman
Absorption

Slow- 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 binding

Protein 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.

Route of elimination

About 69% was recovered following 21 days after a single dose of vandentanib. 44% was found in feces and 25% in urine.

Half life

Median half life of 19 days.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vandetanib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Vandetanib.Experimental
AmiodaroneThe metabolism of Vandetanib can be decreased when combined with Amiodarone.Approved, Investigational
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Vandetanib.Approved, Investigational, Withdrawn
AprepitantThe serum concentration of Vandetanib can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Vandetanib can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Vandetanib can be decreased when combined with Atomoxetine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Vandetanib.Approved, Investigational
BoceprevirThe metabolism of Vandetanib can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Vandetanib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Vandetanib can be decreased when it is combined with Bosentan.Approved, Investigational
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
ClarithromycinThe metabolism of Vandetanib can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Vandetanib can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Vandetanib can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Vandetanib can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Vandetanib.Approved, Investigational
CrizotinibThe metabolism of Vandetanib can be decreased when combined with Crizotinib.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
CymarinCymarin may decrease the cardiotoxic activities of Vandetanib.Experimental
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
DelavirdineThe metabolism of Vandetanib can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Vandetanib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Vandetanib.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Vandetanib.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of 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
DoxycyclineThe metabolism of Vandetanib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Vandetanib can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Vandetanib can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Vandetanib can be decreased when combined with Erythromycin.Approved, Vet Approved
FluconazoleThe metabolism of Vandetanib can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Vandetanib can be decreased when combined with Fluvoxamine.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
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
GitoformateGitoformate may decrease the cardiotoxic activities of Vandetanib.Experimental
IdelalisibThe metabolism of Vandetanib can be decreased when combined with Idelalisib.Approved
ImatinibThe metabolism of Vandetanib can be decreased when combined with Imatinib.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
IsradipineThe metabolism of Vandetanib can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Vandetanib can be decreased when combined with Itraconazole.Approved, Investigational
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
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Vandetanib.Experimental
LopinavirThe metabolism of Vandetanib can be decreased when combined with Lopinavir.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
MacimorelinVandetanib may increase the QTc-prolonging activities of Macimorelin.Approved, Investigational
MetforminThe serum concentration of Metformin can be increased when it is combined with Vandetanib.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Vandetanib.Experimental
MifepristoneThe serum concentration of Vandetanib can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Vandetanib can be decreased when it is combined with Mitotane.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
NilotinibThe metabolism of Vandetanib can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Vandetanib can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Vandetanib.Experimental, Investigational
OsimertinibThe serum concentration of Vandetanib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Vandetanib.Approved
PalbociclibThe serum concentration of Vandetanib can be increased when it is combined with Palbociclib.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Vandetanib.Approved
PentobarbitalThe serum concentration of Vandetanib can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Vandetanib.Experimental
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
PosaconazoleThe metabolism of Vandetanib can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe serum concentration of Vandetanib can be decreased when it is combined with Primidone.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Vandetanib.Experimental
RanolazineThe metabolism of Vandetanib can be decreased when combined with Ranolazine.Approved, Investigational
RibociclibThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Vandetanib.Approved
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
RucaparibThe metabolism of Vandetanib can be decreased when combined with Rucaparib.Approved, Investigational
SaquinavirThe metabolism of Vandetanib can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Vandetanib can be decreased when used in combination with Sarilumab.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
St. John's WortThe serum concentration of Vandetanib can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Vandetanib can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Vandetanib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Vandetanib can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Vandetanib can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of Vandetanib can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Vandetanib can be decreased when it is combined with Tocilizumab.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Vandetanib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Vandetanib.Approved, Investigational
VemurafenibThe serum concentration of Vandetanib can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Vandetanib can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Vandetanib can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Vandetanib can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Vandetanib can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

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
KEGG Drug
D06407
PubChem Compound
3081361
PubChem Substance
175426969
ChemSpider
2338979
BindingDB
21
ChEBI
49960
ChEMBL
CHEMBL24828
PharmGKB
PA166118341
HET
ZD6
Wikipedia
Vandetanib
ATC Codes
L01XE12 — Vandetanib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2ivu
FDA label
Download (220 KB)
MSDS
Download (220 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentCancers / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedBasic Science(t1/2,λz) / Cmax / Pharmacokinetics / Plasma [AUC(0-672)] / Plasma [AUC(0-t)] / Plasma AUC / Tmax1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedTreatmentAdenocarcinomas / Colorectal / Metastatic1
1CompletedTreatmentAdvanced Colorectal Carcinoma1
1CompletedTreatmentAdvanced Incurable Solid Malignancy1
1CompletedTreatmentAdvanced Solid, Malignant Tumors1
1CompletedTreatmentAnal, Colon, and Rectal Cancers / Colon/Rectal Cancer / Neoplasms, Colorectal1
1CompletedTreatmentBiliary Cancer / Malignant Neoplasm of Pancreas / Malignant Solid Tumours1
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentCarcinoma NOS / Lung Cancers / Non-Small Cell Lung1
1CompletedTreatmentColorectal Cancers2
1CompletedTreatmentDiffuse Intrinsic Pontine Glioma (DIPG)1
1CompletedTreatmentGlioblastomas1
1CompletedTreatmentGlioblastomas / Gliosarcoma2
1CompletedTreatmentHead and Neck Carcinoma1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentLung Cancers / Lymphoproliferative Disorders / Malignant Lymphomas / Small Intestine Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentMalignant Gliomas1
1CompletedTreatmentMalignant Gliomas / Progressive Low-Grade Gliomas / Recurrent High-Grade Gliomas1
1CompletedTreatmentMalignant Neoplasm of Pancreas1
1CompletedTreatmentMetastatic Breast Cancer (MBC)1
1RecruitingTreatmentAdvanced Cancers1
1TerminatedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Esophageal Cancers1
1TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
1TerminatedTreatmentNeuroblastomas1
1Unknown StatusTreatmentCancer of the Esophagus, Gastroesophageal Junction or Stomach1
1WithdrawnTreatmentCancer, Breast / Head and Neck Carcinoma / Lung Cancers / Prostate Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1WithdrawnTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
1WithdrawnTreatmentParaganglioma / Phaeochromocytoma1
1WithdrawnTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2Active Not RecruitingTreatmentGlioblastoma Multiforme / Gliosarcoma1
1, 2Active Not RecruitingTreatmentMedullary Thyroid Cancer (MTC)1
1, 2Active Not RecruitingTreatmentMedullary Thyroid Cancer (MTC) / Multiple Endocrine Neoplasia Type 2a / Multiple Endocrine Neoplasia Type 2B1
1, 2CompletedTreatmentUnresectable Locally Advanced or Metastatic, Medullary Thyroid Carcinoma1
1, 2RecruitingTreatmentHereditary Leiomyomatosis and Renal Cell Cancer / Papillary Renal Cell Carcinoma, Sporadic / Renal Cell Adenocarcinoma1
1, 2TerminatedTreatmentCancer, Ovarian1
2Active Not RecruitingTreatmentGIST1
2Active Not RecruitingTreatmentNeoplasms, Thyroid1
2Active Not RecruitingTreatmentThyroid Cancers1
2CompletedTreatmentAdvanced Breast Cancer1
2CompletedTreatmentAmpullary Carcinoma / Biliary Tract Cancer / Cancer Of The Extrahepatic Bile Duct / Gallbladder Cancer1
2CompletedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Mixed Oligoastrocytoma / Anaplastic Oligodendroglioma (AO) / Glioblastoma Multiforme / Gliosarcoma1
2CompletedTreatmentBladder Cancers / Transitional Cell Carcinoma1
2CompletedTreatmentCancer, Ovarian / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentCancers / Colorectal1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentHepatocellular,Carcinoma1
2CompletedTreatmentHormone Refractory / Metastatic / Prostate Cancer1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)4
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2CompletedTreatmentLung Cancers2
2CompletedTreatmentMetastatic Breast Cancer (MBC)1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentNeoplasm Metastases / Neoplasms, Breast1
2CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentNon-Small Cell Lung Cancer (NSCLC, Locally Advanced or Metastatic, Second-line1
2CompletedTreatmentProstate Cancer2
2CompletedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
2CompletedTreatmentThyroid Cancers1
2RecruitingPreventionLip and Oral Cavity Squamous Cell Carcinoma / Oral Cavity Verrucous Carcinoma / Precancerous Conditions1
2RecruitingTreatmentBreast Cancer Invasive Nos1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
2RecruitingTreatmentNeoplasms1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2TerminatedTreatmentAbdominal wall neoplasm / Fallopian Tube Neoplasms / Neoplasms, Ovarian1
2TerminatedTreatmentAdvanced Clear Cell Renal Carcinoma1
2TerminatedTreatmentCancer, Breast2
2TerminatedTreatmentHead and Neck Carcinoma1
2TerminatedTreatmentLung Cancers2
2TerminatedTreatmentLung Cancers / Pleural Effusions1
2TerminatedTreatmentMalignant Neoplasm of Stomach1
2TerminatedTreatmentMesothelioma1
2TerminatedTreatmentProstate Cancer1
2Unknown StatusTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter / Ureteral Cancer / Urethral Cancer1
2Unknown StatusTreatmentMalignant Neoplasm of Pancreas1
2WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Active Not RecruitingTreatmentDifferentiated Thyroid Cancer (DTC)1
3Active Not RecruitingTreatmentLocally Advanced or Metastatic Medullary Thyroid Cancer / Medullary Thyroid Cancer (MTC)1
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
3Active Not RecruitingTreatmentThyroid Cancers1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
4Active Not RecruitingTreatmentThyroid Cancers1
Not AvailableCompletedNot AvailableAll Belgian Patients With Aggressive, Symptomatic Unresectable Locally Advanced or Metastatic Medullary Thyroid Cancer and Taking Caprelsa® Will be Included1
Not AvailableRecruitingNot AvailableAdvanced/Metastatic Medullary Thyroid Cancer (MTC) / Symptomatic, Aggressive, Sporadic, Unresectable, Locally1
Not AvailableRecruitingDiagnosticCancers / High-Grade Gliomas1
Not AvailableRecruitingTreatmentGastrointestinal Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral300 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral300 mg
TabletOral100 mg/1
TabletOral300 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8642608No2002-02-062022-02-06Us
US8067427No2008-08-082028-08-08Us
US7173038No2001-08-142021-08-14Us
USRE42353No1997-09-232017-09-23Us

Properties

State
Solid
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 RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Download (103 KB)
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/MSsplash10-000i-0293000000-9037b32a179af5e7ba9a

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinazolinamines
Alternative Parents
Aniline and substituted anilines / Anisoles / Alkyl aryl ethers / Aminopyrimidines and derivatives / Bromobenzenes / Fluorobenzenes / Piperidines / Aryl bromides / Imidolactams / Aryl fluorides
show 8 more
Substituents
Quinazolinamine / Anisole / Aniline or substituted anilines / Alkyl aryl ether / Aminopyrimidine / Bromobenzene / Fluorobenzene / Halobenzene / Aryl bromide / Aryl fluoride
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, organofluorine compound, organobromine compound, aromatic ether, secondary amine, quinazolines (CHEBI:49960)

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...
Gene Name
VEGFA
Uniprot ID
P15692
Uniprot Name
Vascular endothelial growth factor A
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, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
References
  1. Link [Link]
Details
3. Protein-tyrosine kinase 6
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. F...
Gene Name
PTK6
Uniprot ID
Q13882
Uniprot Name
Protein-tyrosine kinase 6
Molecular Weight
51833.72 Da
References
  1. Link [Link]
Details
4. Angiopoietin-1 receptor
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...
Gene Name
TEK
Uniprot ID
Q02763
Uniprot Name
Angiopoietin-1 receptor
Molecular Weight
125829.005 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

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
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 1
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 impor...
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
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 colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
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, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
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 fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
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]

Drug created on November 18, 2007 11:23 / Updated on January 15, 2018 08:55