vandetanib 🐶 Veterinary Use | 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: OFP

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

Drug dosage:

DoseUnitRoute
0.30 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
S (Water solubility) 0.01 mg/mL Bocci G, Oprea TI, Benet LZ

Approvals:

DateAgencyCompanyOrphan
Feb. 16, 2012 EMA GENZYME EUROPE BV
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 150.65 34.55 55 1401 59475 63428091
Reflux gastritis 86.03 34.55 16 1440 1179 63486387
Hypophosphataemia 67.10 34.55 20 1436 11406 63476160
Facial paralysis 63.03 34.55 20 1436 14021 63473545
Lymphocyte count decreased 61.93 34.55 24 1432 30233 63457333
Ataxia 61.48 34.55 20 1436 15175 63472391
Blood triglycerides increased 61.11 34.55 19 1437 12469 63475097
Myoclonus 60.63 34.55 20 1436 15848 63471718
Hypophagia 54.20 34.55 22 1434 31237 63456329
Hemiparesis 53.13 34.55 20 1436 23262 63464304
Ocular hyperaemia 51.63 34.55 20 1436 25124 63462442
Flatulence 45.41 34.55 20 1436 34682 63452884
Neutrophil count decreased 44.65 34.55 23 1433 56383 63431183
Malignant neoplasm progression 44.34 34.55 26 1430 82095 63405471
Disease progression 44.06 34.55 30 1426 122728 63364838
Abdominal distension 37.96 34.55 24 1432 86591 63400975
Metastases to liver 35.42 34.55 15 1441 23624 63463942

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 79.31 34.95 29 591 40923 34915388
Blood calcitonin increased 49.82 34.95 6 614 25 34956286
Diarrhoea 43.58 34.95 43 577 389869 34566442
Acne 37.67 34.95 12 608 11054 34945257

FDA Adverse Event Reporting System (Geriatric)

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 173.33 32.29 70 1936 90316 79652066
Reflux gastritis 83.82 32.29 16 1990 1233 79741149
Myoclonus 54.79 32.29 22 1984 27638 79714744
Hypophosphataemia 54.34 32.29 20 1986 19893 79722489
Blood calcitonin increased 53.38 32.29 7 1999 43 79742339
Facial paralysis 53.23 32.29 20 1986 21052 79721330
Diarrhoea 52.47 32.29 85 1921 880404 78861978
Ataxia 49.88 32.29 20 1986 25019 79717363
Blood triglycerides increased 49.65 32.29 19 1987 21021 79721361
Lymphocyte count decreased 49.43 32.29 24 1982 47265 79695117
Ocular hyperaemia 47.58 32.29 20 1986 28186 79714196
Flatulence 45.60 32.29 22 1984 42702 79699680
Malignant neoplasm progression 45.44 32.29 33 1973 135957 79606425
Acne 44.93 32.29 19 1987 27171 79715211
Hypophagia 44.35 32.29 22 1984 45345 79697037
Hemiparesis 44.14 32.29 20 1986 33713 79708669
Hypertension 43.05 32.29 47 1959 330945 79411437
Metastases to liver 40.92 32.29 18 1988 28296 79714086
Metastases to bone 40.13 32.29 17 1989 24410 79717972

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EX04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Other protein kinase inhibitors
FDA MoA N0000175076 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000187061 Organic Cation Transporter 2 Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:38637 tyrosine kinase inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Medullary thyroid carcinoma indication 255032005 DOID:3973
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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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)

None

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
Tyrosine-protein kinase ABL1 Kinase Kd 8.05 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase Kd 7.47 CHEMBL
Breakpoint cluster region protein Kinase Kd 6.06 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase INHIBITOR Kd 7.15 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 7.77 CHEMBL
Tyrosine-protein kinase Yes Kinase Kd 6.92 CHEMBL
Tyrosine-protein kinase Fyn Kinase Kd 6.44 CHEMBL
Ephrin type-A receptor 2 Kinase INHIBITOR Kd 5.96 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 6.72 CHEMBL
Vascular endothelial growth factor receptor 1 Kinase INHIBITOR Kd 6.59 CHEMBL
Vascular endothelial growth factor receptor 3 Kinase INHIBITOR Kd 6.52 CHEMBL
Macrophage colony-stimulating factor 1 receptor Kinase Kd 5.92 CHEMBL
Platelet-derived growth factor receptor alpha Kinase Kd 6.64 CHEMBL
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR Kd 5.59 CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform Kinase Kd 5.10 CHEMBL
Fibroblast growth factor receptor 3 Kinase Kd 6.62 CHEMBL
Tyrosine-protein kinase HCK Kinase Kd 6.44 CHEMBL
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR Kd 6.32 CHEMBL
Rho-associated protein kinase 2 Kinase Kd 5.44 CHEMBL
Tyrosine-protein kinase CSK Kinase Kd 5.60 CHEMBL
Angiopoietin-1 receptor Kinase INHIBITOR Kd 6 CHEMBL
Ephrin type-A receptor 8 Kinase INHIBITOR Kd 7.04 CHEMBL
Hepatocyte growth factor receptor Kinase Kd 5.39 CHEMBL
Tyrosine-protein kinase Lyn Kinase Kd 6.96 CHEMBL
5'-AMP-activated protein kinase catalytic subunit alpha-1 Kinase Kd 5.52 CHEMBL
Fibroblast growth factor receptor 1 Kinase Kd 6.25 CHEMBL
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform Kinase Kd 5.96 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 7.09 CHEMBL
Serine/threonine-protein kinase PLK4 Kinase Kd 6.21 CHEMBL
Aurora kinase C Kinase Kd 5.82 CHEMBL
Abelson tyrosine-protein kinase 2 Kinase Kd 7.16 CHEMBL
Ephrin type-A receptor 5 Kinase INHIBITOR Kd 6.62 CHEMBL
Ephrin type-A receptor 4 Kinase INHIBITOR Kd 5.80 CHEMBL
Fibroblast growth factor receptor 2 Kinase Kd 5.96 CHEMBL
Ephrin type-A receptor 6 Kinase INHIBITOR Kd 7.30 CHEMBL
TRAF2 and NCK-interacting protein kinase Kinase Kd 5.64 CHEMBL
Casein kinase I isoform epsilon Kinase Kd 5.82 CHEMBL
Tyrosine-protein kinase Fgr Kinase Kd 6.57 CHEMBL
ALK tyrosine kinase receptor Kinase Kd 5.68 CHEMBL
Ephrin type-A receptor 3 Kinase INHIBITOR Kd 5.74 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 6.77 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 5 Kinase Kd 6.35 CHEMBL
Mitogen-activated protein kinase kinase kinase 4 Kinase Kd 5.52 CHEMBL
Cyclin-G-associated kinase Kinase Kd 7.07 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 8.34 CHEMBL
Ephrin type-B receptor 1 Kinase INHIBITOR Kd 6.54 CHEMBL
Ephrin type-A receptor 7 Kinase INHIBITOR Kd 5.62 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
Epithelial discoidin domain-containing receptor 1 Kinase Kd 7.96 CHEMBL
Ephrin type-B receptor 4 Kinase INHIBITOR Kd 6.28 CHEMBL
Serine/threonine-protein kinase receptor R3 Kinase Kd 6.33 CHEMBL
Activin receptor type-1 Kinase Kd 6.82 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 1 Kinase Kd 5.74 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 2 Kinase Kd 5.96 CHEMBL
Protein-tyrosine kinase 6 Kinase INHIBITOR Kd 7.48 CHEMBL
Tyrosine-protein kinase BTK Kinase Kd 5.77 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 6.60 CHEMBL
Tyrosine-protein kinase receptor TYRO3 Kinase Kd 7.03 CHEMBL
Ephrin type-B receptor 2 Kinase INHIBITOR Kd 6.36 CHEMBL
Cyclin-dependent kinase 7 Kinase Kd 5.39 CHEMBL
Ribosomal protein S6 kinase beta-1 Kinase Kd 5.80 CHEMBL
Ribosomal protein S6 kinase alpha-6 Kinase Kd 6.62 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase Kd 5.29 CHEMBL
Tyrosine-protein kinase receptor Tie-1 Kinase Kd 5.82 CHEMBL
Tyrosine-protein kinase TXK Kinase Kd 5.43 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 1 Kinase Kd 6.44 CHEMBL
Serine/threonine-protein kinase SIK2 Kinase Kd 6.37 CHEMBL
Serine/threonine-protein kinase 33 Kinase Kd 5.85 CHEMBL
Serine/threonine-protein kinase TNNI3K Kinase Kd 5.55 CHEMBL
Discoidin domain-containing receptor 2 Kinase Kd 6.49 CHEMBL
Chaperone activity of bc1 complex-like, mitochondrial Kinase Kd 5.35 CHEMBL
Serine/threonine-protein kinase MRCK gamma Kinase Kd 5.66 CHEMBL
Leukocyte tyrosine kinase receptor Kinase Kd 6.26 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1 Kinase Kd 5.26 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 3 Kinase Kd 5.82 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 7.18 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 4 Kinase Kd 5.85 CHEMBL
Tyrosine-protein kinase Mer Kinase Kd 5.85 CHEMBL
Serine/threonine-protein kinase MRCK alpha Kinase Kd 5.59 CHEMBL
Serine/threonine-protein kinase MRCK beta Kinase Kd 5.60 CHEMBL
Citron Rho-interacting kinase Kinase Kd 5.74 CHEMBL
AarF domain-containing protein kinase 4 Kinase Kd 5.77 CHEMBL
Serine/threonine-protein kinase SIK1 Kinase Kd 5.72 CHEMBL
Tyrosine-protein kinase Srms Kinase Kd 5.72 CHEMBL
Dual specificity testis-specific protein kinase 1 Kinase Kd 5.43 CHEMBL
Ephrin type-A receptor 1 Kinase INHIBITOR Kd 6.64 CHEMBL
Mitogen-activated protein kinase 6 Kinase Kd 5.82 CHEMBL
Fibroblast growth factor receptor 4 Kinase Kd 5.64 CHEMBL
Ribosomal protein S6 kinase alpha-1 Kinase Kd 6.40 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2 Kinase Kd 5.80 CHEMBL
Misshapen-like kinase 1 Kinase Kd 5.47 CHEMBL
Interleukin-1 receptor-associated kinase 4 Kinase Kd 7.12 CHEMBL
Ephrin type-B receptor 6 Kinase INHIBITOR Kd 7.12 CHEMBL
Hormonally up-regulated neu tumor-associated kinase Kinase Kd 5.39 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 5.92 CHEMBL
Serine/threonine-protein kinase ULK3 Kinase Kd 5.19 CHEMBL
Mitogen-activated protein kinase kinase kinase 19 Kinase Kd 6.01 CHEMBL
Receptor-interacting serine/threonine-protein kinase 4 Kinase Kd 6.21 CHEMBL
Serine/threonine-protein kinase 35 Kinase Kd 7.25 CHEMBL
Receptor tyrosine-protein kinase erbB-3 Kinase INHIBITOR Kd 6.80 CHEMBL
Serine/threonine-protein kinase SIK3 Kinase Kd 5.41 CHEMBL
Bone morphogenetic protein receptor type-1B Kinase Kd 6.62 CHEMBL
Serine/threonine-protein kinase 32A Kinase Kd 5.30 CHEMBL
Macrophage-stimulating protein receptor Kinase IC50 5.47 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 7.31 CHEMBL
ATP-binding cassette sub-family G member 2 Transporter IC50 6.70 CHEMBL
Platelet-derived growth factor receptor beta Kinase Kd 7.06 CHEMBL
Tubulin alpha-1A chain Structural Kd 6.32 CHEMBL

External reference:

IDSource
4030726 VUID
N0000182736 NUI
D06407 KEGG_DRUG
4030726 VANDF
C1121849 UMLSCUI
CHEBI:49960 CHEBI
ZD6 PDB_CHEM_ID
CHEMBL24828 ChEMBL_ID
DB05294 DRUGBANK_ID
C452423 MESH_SUPPLEMENTAL_RECORD_UI
5717 IUPHAR_LIGAND_ID
8365 INN_ID
YO460OQ37K UNII
3081361 PUBCHEM_CID
1098413 RXNORM
181099 MMSL
189346 MMSL
27846 MMSL
d07761 MMSL
013703 NDDF
418260004 SNOMEDCT_US
418520004 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7820 TABLET, FILM COATED 100 mg ORAL NDA 32 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7820 TABLET, FILM COATED 100 mg ORAL NDA 32 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7820 TABLET, FILM COATED 100 mg ORAL NDA 32 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7840 TABLET, FILM COATED 300 mg ORAL NDA 32 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7840 TABLET, FILM COATED 300 mg ORAL NDA 32 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7840 TABLET, FILM COATED 300 mg ORAL NDA 32 sections
CAPRELSA HUMAN PRESCRIPTION DRUG LABEL 1 58468-7860 TABLET, FILM COATED 300 mg ORAL UNAPPROVED DRUG FOR USE IN DRUG SHORTAGE 4 sections