NAV

Vatalanib

Identification

Generic Name
Vatalanib
DrugBank Accession Number
DB04879
Background

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.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 346.813
Monoisotopic: 346.098524207
Chemical Formula
C20H15ClN4
Synonyms
  • Vatalanib
  • Vatalinib
External IDs
  • BAY-86-5127
  • CGP 79787
  • CGP-79787
  • CGP-797870
  • K-222584
  • NVP-PTK787
  • PTK 787
  • PTK/ZK
  • PTK787/ZK 222584
  • ZK-232934
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Pharmacology

Indication

Used in combination with first- and second-line chemotherapy for the treatment of metastatic colorectal cancer and non-small cell lung cancer (NSCLC).

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Vatalanib 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 action

Vatalanib 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.

TargetActionsOrganism
UVascular endothelial growth factor receptor 1Not AvailableHumans
UVascular endothelial growth factor receptor 2Not AvailableHumans
UVascular endothelial growth factor receptor 3Not AvailableHumans
Absorption

Rapid onset of absorption

Volume of distribution

Not Available

Protein binding

Not 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 elimination

Not Available

Half-life

Approximately 6 hours.

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
PathwayCategory
Vatalanib Action PathwayDrug action
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Vatalanib.
CarbimazoleThe therapeutic efficacy of Carbimazole can be decreased when used in combination with Vatalanib.
FollitropinThe therapeutic efficacy of Follitropin can be decreased when used in combination with Vatalanib.
LevothyroxineThe therapeutic efficacy of Levothyroxine can be decreased when used in combination with Vatalanib.
LiothyronineThe therapeutic efficacy of Liothyronine can be decreased when used in combination with Vatalanib.
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Phthalazines
Alternative Parents
Aniline and substituted anilines / Chlorobenzenes / Aminopyridazines / Pyridines and derivatives / Imidolactams / Aryl chlorides / Heteroaromatic compounds / Secondary amines / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Amine / Aminopyridazine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Chlorobenzene / Halobenzene
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
5DX9U76296
CAS number
212141-54-3
InChI Key
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-yl)methyl]phthalazin-1-amine
SMILES
ClC1=CC=C(NC2=NN=C(CC3=CC=NC=C3)C3=CC=CC=C23)C=C1

References

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. [Article]
  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. [Article]
  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. [Article]
PubChem Compound
151194
PubChem Substance
175426883
ChemSpider
133257
BindingDB
4851
ChEBI
90620
ChEMBL
CHEMBL101253
ZINC
ZINC000000007460
PharmGKB
PA7001
Wikipedia
Vatalanib

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3CompletedTreatmentColon Neoplasm / Colorectal Neoplasms / Rectal Neoplasms2
2CompletedTreatmentBrain and Central Nervous System Tumors / Sarcomas1
2CompletedTreatmentCNS Hemangioblastoma / Retinal Hemangioblastoma / Von Hippel-Lindau Disease1
2CompletedTreatmentLeukemias / Myelodysplastic Syndrome / Myeloproliferative/Myelodysplastic Neoplasm1
2CompletedTreatmentMalignant Pleural Mesothelioma (MPM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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 RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-001i-3927000000-196ba8be28b2e322cff7
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0019000000-6ef94e2bc6482e0ee45d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0009000000-bd5c18660abe18b2a7da
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0009000000-5904bcc7619bac424806
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0009000000-4f646d487bd073fc1796
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-5797000000-b0ab4fac568ff2814728
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9230000000-6b455f8dfce2c0690381
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-181.48051
predicted
DeepCCS 1.0 (2019)
[M+H]+183.83853
predicted
DeepCCS 1.0 (2019)
[M+Na]+190.89183
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Vascular endothelial growth factor receptor 1
Kind
Protein
Organism
Humans
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 ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
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. [Article]
Details2. Vascular endothelial growth factor receptor 2
Kind
Protein
Organism
Humans
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 ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
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. [Article]
Details3. Vascular endothelial growth factor receptor 3
Kind
Protein
Organism
Humans
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 cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
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. [Article]

Drug created at October 20, 2007 19:26 / Updated at February 21, 2021 18:51