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Identification
NameVatalanib
Accession NumberDB04879
TypeSmall Molecule
GroupsInvestigational
Description

Vatalanib (PTK787/ZK-222584) is a new oral antiangiogenic molecule that inhibits all known vascular endothelial growth factor receptors. Vatalanib is under investigation for the treatment of solid tumors.

Structure
Thumb
Synonyms
1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine succinate
PTK 787
PTK/ZK
External Identifiers
  • CGP 79787
  • CGP-797870
  • PTK787/ZK 222584
  • ZK-232934
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII5DX9U76296
CAS number212141-54-3
WeightAverage: 346.813
Monoisotopic: 346.098524207
Chemical FormulaC20H15ClN4
InChI KeyInChIKey=YCOYDOIWSSHVCK-UHFFFAOYSA-N
InChI
InChI=1S/C20H15ClN4/c21-15-5-7-16(8-6-15)23-20-18-4-2-1-3-17(18)19(24-25-20)13-14-9-11-22-12-10-14/h1-12H,13H2,(H,23,25)
IUPAC Name
N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine
SMILES
ClC1=CC=C(NC2=NN=C(CC3=CC=NC=C3)C3=CC=CC=C23)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phthalazines. These are compounds containing a phthalazine moiety, which consists of a benzene ring fused to a pyridazine, forming a 2,3-benzodiazine skeleton.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassPhthalazines
Direct ParentPhthalazines
Alternative Parents
Substituents
  • Phthalazine
  • Halobenzene
  • Chlorobenzene
  • Aminopyridazine
  • Imidolactam
  • Benzenoid
  • Pyridine
  • Pyridazine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Azacycle
  • Secondary amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed in combination with first- and second-line chemotherapy for the treatment of metastatic colorectal cancer and non-small cell lung cancer (NSCLC).
PharmacodynamicsVatalanib is a novel oral angiogenesis inhibitor being developed by Schering (in collaboration with Novartis AG). Vatalanib selectively inhibits the tyrosine kinase domains of vascular endothelial growth factor (VEGF) receptors, platelet-derived growth factor (PDGF) receptor, and c-KIT.
Mechanism of actionVatalanib potently inhibits vascular endothelial growth factor (VEGF) receptor tyrosine kinases, important enzymes in the formation of new blood vessels that contribute to tumor growth and metastasis.
Related Articles
AbsorptionRapid onset of absorption
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Mainly through oxidative metabolism. Two pharmacologically inactive metabolites, CGP 84368/ZK 260120 and NVP AAW378/ZK 261557, having systemic exposure comparable to that of vatalanib, contributed mainly to the total systemic exposure.

Route of eliminationNot Available
Half lifeApproximately 6 hours.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Vatalanib Action PathwayDrug actionSMP00421
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.994
Blood Brain Barrier+0.9829
Caco-2 permeable+0.6936
P-glycoprotein substrateNon-substrate0.642
P-glycoprotein inhibitor INon-inhibitor0.8083
P-glycoprotein inhibitor IINon-inhibitor0.8599
Renal organic cation transporterNon-inhibitor0.6742
CYP450 2C9 substrateNon-substrate0.8868
CYP450 2D6 substrateNon-substrate0.8483
CYP450 3A4 substrateNon-substrate0.6173
CYP450 1A2 substrateInhibitor0.9209
CYP450 2C9 inhibitorInhibitor0.637
CYP450 2D6 inhibitorInhibitor0.5654
CYP450 2C19 inhibitorInhibitor0.8432
CYP450 3A4 inhibitorInhibitor0.6922
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8539
Ames testAMES toxic0.5592
CarcinogenicityNon-carcinogens0.803
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4258 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7061
hERG inhibition (predictor II)Non-inhibitor0.8813
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00179 mg/mLALOGPS
logP4.5ALOGPS
logP4.15ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)15.17ChemAxon
pKa (Strongest Basic)4.95ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area50.7 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity100.98 m3·mol-1ChemAxon
Polarizability36.52 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Yamamoto A, Watanabe H, Sueki H, Nakanishi T, Yasuhara H, Iijima M: Vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK 222584 inhibits both the induction and elicitation phases of contact hypersensitivity. J Dermatol. 2007 Jul;34(7):419-29. [PubMed:17584317 ]
  2. Lijnen HR, Van Hoef B, Kemp D, Collen D: Inhibition of vascular endothelial growth factor receptor tyrosine kinases impairs adipose tissue development in mouse models of obesity. Biochim Biophys Acta. 2007 Sep;1770(9):1369-73. Epub 2007 Jun 15. [PubMed:17616257 ]
  3. Jost LM, Gschwind HP, Jalava T, Wang Y, Guenther C, Souppart C, Rottmann A, Denner K, Waldmeier F, Gross G, Masson E, Laurent D: Metabolism and disposition of vatalanib (PTK787/ZK-222584) in cancer patients. Drug Metab Dispos. 2006 Nov;34(11):1817-28. Epub 2006 Aug 1. [PubMed:16882767 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Vegf-b-activated receptor activity
Specific Function:
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation ...
Gene Name:
FLT1
Uniprot ID:
P17948
Molecular Weight:
150767.185 Da
References
  1. Yamamoto A, Watanabe H, Sueki H, Nakanishi T, Yasuhara H, Iijima M: Vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK 222584 inhibits both the induction and elicitation phases of contact hypersensitivity. J Dermatol. 2007 Jul;34(7):419-29. [PubMed:17584317 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Vascular endothelial growth factor-activated receptor activity
Specific Function:
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domai...
Gene Name:
KDR
Uniprot ID:
P35968
Molecular Weight:
151525.555 Da
References
  1. Yamamoto A, Watanabe H, Sueki H, Nakanishi T, Yasuhara H, Iijima M: Vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK 222584 inhibits both the induction and elicitation phases of contact hypersensitivity. J Dermatol. 2007 Jul;34(7):419-29. [PubMed:17584317 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Vascular endothelial growth factor-activated receptor activity
Specific Function:
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced pr...
Gene Name:
FLT4
Uniprot ID:
P35916
Molecular Weight:
152755.94 Da
References
  1. Yamamoto A, Watanabe H, Sueki H, Nakanishi T, Yasuhara H, Iijima M: Vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK 222584 inhibits both the induction and elicitation phases of contact hypersensitivity. J Dermatol. 2007 Jul;34(7):419-29. [PubMed:17584317 ]
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Drug created on October 20, 2007 13:26 / Updated on September 16, 2013 17:26