vandetanib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
angiogenesis inhibitors 4178 443913-73-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ZD-6474
  • vandetanib
  • zactima
  • caprelsa
  • ZD6474
In vitro studies have shown that vandetanib inhibits the tyrosine kinase activity of the EGFR and VEGFR families, RET, BRK, TIE2, and members of the EPH receptor and Src kinase families. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. In addition, the N-desmethyl metabolite of the drug, representing 7 to 17.1% of vandetanib exposure, has similar inhibitory activity to the parent compound for VEGF receptors (KDR and Flt-1) and EGFR. In vitro, vandetanib inhibited epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. In vivo, vandetanib administration reduced tumor cell-induced angiogenesis, tumor vessel permeability, and inhibited tumor growth and metastasis in mouse models of cancer.
  • Molecular weight: 475.36
  • Formula: C22H24BrFN4O2
  • CLOGP: 5.69
  • LIPINSKI: 1
  • HAC: 6
  • HDO: 1
  • TPSA: 59.51
  • ALOGS: -4.67
  • ROTB: 6

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ

Approvals:

DateAgencyCompanyOrphan
April 6, 2011 FDA IPR PHARMS INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Electrocardiogram QT prolonged 119.48 39.27 27 248 7787 2350023
Diarrhoea 75.89 39.27 33 242 83531 2274279
Metastases to bone 52.05 39.27 11 264 2258 2355552
Metastases to liver 49.21 39.27 11 264 2930 2354880
Metastases to central nervous system 41.25 39.27 9 266 2139 2355671
Rash 39.33 39.27 19 256 59539 2298271

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Electrocardiogram QT prolonged 117.39 36.51 28 278 5517 1740958
Diarrhoea 64.08 36.51 31 275 53821 1692654
Photosensitivity reaction 48.20 36.51 11 295 1739 1744736
Disease progression 36.56 36.51 15 291 17248 1729227

Pharmacologic Action:

SourceCodeDescription
ATC L01XE12 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175076 Protein Kinase Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000187061 Organic Cation Transporter 2 Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Carcinoma of thyroid indication 448216007
Hypocalcemia contraindication 5291005
Torsades de pointes contraindication 31722008
Hypertensive disorder contraindication 38341003 DOID:10763
Hypothyroidism contraindication 40930008 DOID:1459
Hypokalemia contraindication 43339004
Heart failure contraindication 84114007 DOID:6000
Prolonged QT interval contraindication 111975006
Hypomagnesemia contraindication 190855004
Impaired renal function disorder contraindication 197663003
Interstitial lung disease contraindication 233703007 DOID:3082
Cerebral ischemia contraindication 287731003
Pregnancy, function contraindication 289908002
Severe diarrhea contraindication 409587002
Breastfeeding (mother) contraindication 413712001
Congenital long QT syndrome contraindication 442917000
Posterior reversible encephalopathy syndrome contraindication 450886002
Significant Bleeding contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.58 Basic
pKa2 5.88 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG CAPRELSA GENZYME CORP N022405 April 6, 2011 RX TABLET ORAL 8642608 Feb. 6, 2022 FOR USE IN PATIENTS HAVING SYMPTOMATIC OR PROGRESSIVE MEDULLARY THYROID CANCER, WITH UNRESECTABLE LOCALLY ADVANCED OR METASTATIC DISEASE
300MG CAPRELSA GENZYME CORP N022405 April 6, 2011 RX TABLET ORAL 8642608 Feb. 6, 2022 FOR USE IN PATIENTS HAVING SYMPTOMATIC OR PROGRESSIVE MEDULLARY THYROID CANCER, WITH UNRESECTABLE LOCALLY ADVANCED OR METASTATIC DISEASE

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase INHIBITOR Kd 7.85 CHEMBL CHEMBL
Epidermal growth factor receptor Kinase INHIBITOR Kd 8.32 CHEMBL CHEMBL
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR Kd 6.33 CHEMBL CHEMBL
Vascular endothelial growth factor receptor 1 Kinase INHIBITOR Kd 6.59 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase INHIBITOR Kd 7.15 CHEMBL
Fibroblast growth factor receptor 3 Kinase Kd 6.62 CHEMBL
Serine/threonine-protein kinase 35 Kinase Kd 7.25 CHEMBL
Fibroblast growth factor receptor 4 Kinase Kd 5.64 CHEMBL
Platelet-derived growth factor receptor alpha Kinase Kd 6.64 CHEMBL
Hepatocyte growth factor receptor Kinase Kd 5.39 CHEMBL
Casein kinase I isoform epsilon Kinase Kd 5.82 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 8.34 CHEMBL
Ephrin type-B receptor 4 Kinase INHIBITOR Kd 6.28 CHEMBL
Ribosomal protein S6 kinase alpha-6 Kinase Kd 6.62 CHEMBL
Ribosomal protein S6 kinase alpha-1 Kinase Kd 6.40 CHEMBL
Cyclin-G-associated kinase Kinase Kd 7.07 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 7.31 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase Kd 5.29 CHEMBL
Tyrosine-protein kinase BTK Kinase Kd 5.77 CHEMBL
Ephrin type-A receptor 1 Kinase INHIBITOR Kd 6.64 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1 Kinase Kd 5.26 CHEMBL
AarF domain-containing protein kinase 4 Kinase Kd 5.77 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 1 Kinase Kd 6.44 CHEMBL
Serine/threonine-protein kinase MRCK alpha Kinase Kd 5.59 CHEMBL
Tyrosine-protein kinase Fgr Kinase Kd 6.57 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 6.77 CHEMBL
Ephrin type-A receptor 8 Kinase INHIBITOR Kd 7.04 CHEMBL
Ephrin type-A receptor 2 Kinase INHIBITOR Kd 5.96 CHEMBL
Ephrin type-A receptor 3 Kinase INHIBITOR Kd 5.74 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 7.09 CHEMBL
Serine/threonine-protein kinase PLK4 Kinase Kd 6.21 CHEMBL
Tyrosine-protein kinase Yes Kinase Kd 6.92 CHEMBL
Tyrosine-protein kinase CSK Kinase Kd 5.60 CHEMBL
Serine/threonine-protein kinase TNNI3K Kinase Kd 5.55 CHEMBL
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR Kd 5.59 CHEMBL
Tyrosine-protein kinase HCK Kinase Kd 6.44 CHEMBL
Aurora kinase C Kinase Kd 5.82 CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform Kinase Kd 5.10 CHEMBL
Platelet-derived growth factor receptor beta Kinase Kd 7.06 CHEMBL
Fibroblast growth factor receptor 1 Kinase Kd 6.25 CHEMBL
Fibroblast growth factor receptor 2 Kinase Kd 5.96 CHEMBL
Citron Rho-interacting kinase Kinase Kd 5.74 CHEMBL
Chaperone activity of bc1 complex-like, mitochondrial Kinase Kd 5.35 CHEMBL
Mitogen-activated protein kinase kinase kinase 4 Kinase Kd 5.52 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 5 Kinase Kd 6.35 CHEMBL
Misshapen-like kinase 1 Kinase Kd 5.47 CHEMBL
Interleukin-1 receptor-associated kinase 4 Kinase Kd 7.12 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase Kd 7.47 CHEMBL
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR Kd 6.32 CHEMBL
Ephrin type-A receptor 6 Kinase INHIBITOR Kd 7.30 CHEMBL
TRAF2 and NCK-interacting protein kinase Kinase Kd 5.64 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 7.02 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2 Kinase Kd 5.77 CHEMBL
Bone morphogenetic protein receptor type-1B Kinase Kd 6.62 CHEMBL
Macrophage-stimulating protein receptor Kinase IC50 5.47 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 5.92 CHEMBL
Ephrin type-A receptor 7 Kinase INHIBITOR Kd 5.62 CHEMBL
Protein-tyrosine kinase 6 Kinase INHIBITOR Kd 7.48 CHEMBL
5'-AMP-activated protein kinase catalytic subunit alpha-1 Kinase Kd 5.52 CHEMBL
Tyrosine-protein kinase Lyn Kinase Kd 6.96 CHEMBL
Ephrin type-A receptor 5 Kinase INHIBITOR Kd 6.62 CHEMBL
Ephrin type-A receptor 4 Kinase INHIBITOR Kd 5.80 CHEMBL
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform Kinase Kd 5.96 CHEMBL
Ephrin type-B receptor 1 Kinase INHIBITOR Kd 6.54 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 3 Kinase Kd 5.82 CHEMBL
Dual specificity testis-specific protein kinase 1 Kinase Kd 5.43 CHEMBL
Activin receptor type-1 Kinase Kd 6.82 CHEMBL
Serine/threonine-protein kinase MRCK gamma Kinase Kd 5.66 CHEMBL
Serine/threonine-protein kinase MRCK beta Kinase Kd 5.60 CHEMBL
Serine/threonine-protein kinase ULK3 Kinase Kd 5.19 CHEMBL
Abelson tyrosine-protein kinase 2 Kinase Kd 7.16 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 7.18 CHEMBL
Angiopoietin-1 receptor Kinase INHIBITOR Kd 6 CHEMBL
Receptor tyrosine-protein kinase erbB-3 Kinase INHIBITOR Kd 6.80 CHEMBL
Ephrin type-B receptor 6 Kinase INHIBITOR Kd 7.12 CHEMBL
Serine/threonine-protein kinase SIK2 Kinase Kd 6.37 CHEMBL
Tyrosine-protein kinase Srms Kinase Kd 5.72 CHEMBL
Cyclin-dependent kinase 7 Kinase Kd 5.39 CHEMBL
Serine/threonine-protein kinase 32A Kinase Kd 5.30 CHEMBL
Serine/threonine-protein kinase SIK3 Kinase Kd 5.41 CHEMBL
Rho-associated protein kinase 2 Kinase Kd 5.44 CHEMBL
Tyrosine-protein kinase Fyn Kinase Kd 6.44 CHEMBL
Macrophage colony-stimulating factor 1 receptor Kinase Kd 5.92 CHEMBL
Vascular endothelial growth factor receptor 3 Kinase INHIBITOR Kd 6.52 CHEMBL
Hormonally up-regulated neu tumor-associated kinase Kinase Kd 5.39 CHEMBL
Discoidin domain-containing receptor 2 Kinase Kd 6.49 CHEMBL
Mitogen-activated protein kinase 6 Kinase Kd 5.82 CHEMBL
Serine/threonine-protein kinase receptor R3 Kinase Kd 6.33 CHEMBL
Tyrosine-protein kinase receptor Tie-1 Kinase Kd 5.82 CHEMBL
Epithelial discoidin domain-containing receptor 1 Kinase Kd 7.96 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 4 Kinase Kd 5.85 CHEMBL
Tyrosine-protein kinase receptor TYRO3 Kinase Kd 7.03 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 7.77 CHEMBL
Leukocyte tyrosine kinase receptor Kinase Kd 6.26 CHEMBL
Mitogen-activated protein kinase kinase kinase 19 Kinase Kd 6.01 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 6.60 CHEMBL
Ephrin type-B receptor 2 Kinase INHIBITOR Kd 6.36 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 2 Kinase Kd 5.96 CHEMBL
Tyrosine-protein kinase TXK Kinase Kd 5.43 CHEMBL
ALK tyrosine kinase receptor Kinase Kd 5.68 CHEMBL
Ribosomal protein S6 kinase beta-1 Kinase Kd 5.80 CHEMBL
Serine/threonine-protein kinase 33 Kinase Kd 5.85 CHEMBL
Receptor-interacting serine/threonine-protein kinase 4 Kinase Kd 6.21 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2 Kinase Kd 5.80 CHEMBL
Serine/threonine-protein kinase SIK1 Kinase Kd 5.72 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 1 Kinase Kd 5.74 CHEMBL
Tyrosine-protein kinase Mer Kinase Kd 5.85 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 6.72 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 8.05 CHEMBL
Tubulin alpha-1A chain Structural Kd 6.32 CHEMBL

External reference:

IDSource
4030726 VUID
N0000182736 NUI
C1628324 UMLSCUI
D06407 KEGG_DRUG
418520004 SNOMEDCT_US
418260004 SNOMEDCT_US
1098413 RXNORM
013703 NDDF
181099 MMSL
27846 MMSL
d07761 MMSL
4030726 VANDF
CHEMBL24828 ChEMBL_ID
ZD6 PDB_CHEM_ID
DB05294 DRUGBANK_ID
CHEBI:49960 CHEBI
YO460OQ37K UNII
8365 INN_ID
3081361 PUBCHEM_CID
5717 IUPHAR_LIGAND_ID
C452423 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 0310-7820 TABLET 100 mg ORAL NDA 20 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 0310-7840 TABLET 300 mg ORAL NDA 20 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7820 TABLET, FILM COATED 100 mg ORAL NDA 20 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7840 TABLET, FILM COATED 300 mg ORAL NDA 20 sections