Explore a selection of our essential drug information below, or:
Overview
- DrugBank ID
- DB04879
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 19
- Phase 2
- 25
- Phase 3
- 2
- Phase 4
- 0
- Mechanism of Action
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
Structure for Vatalanib (DB04879)
- 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
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).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism AEpidermal growth factor receptor inhibitorHumans AVascular endothelial growth factor receptor 3 inhibitorHumans AVascular endothelial growth factor receptor 2 inhibitorHumans AVascular endothelial growth factor receptor 1 inhibitorHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
Pathway Category Vatalanib Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Vatalanib. Carbimazole The therapeutic efficacy of Carbimazole can be decreased when used in combination with Vatalanib. Follitropin The therapeutic efficacy of Follitropin can be decreased when used in combination with Vatalanib. Levothyroxine The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Vatalanib. Liothyronine The 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
- 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]
- 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]
- 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]
- External Links
- PubChem Compound
- 151194
- PubChem Substance
- 175426883
- ChemSpider
- 133257
- BindingDB
- 4851
- ChEBI
- 90620
- ChEMBL
- CHEMBL101253
- ZINC
- ZINC000000007460
- PharmGKB
- PA7001
- Wikipedia
- Vatalanib
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Colon Neoplasm / Colorectal Neoplasms / Rectal Neoplasms 2 somestatus stop reason just information to hide 2 Completed Treatment Brain and Central Nervous System Tumors / Sarcomas 1 somestatus stop reason just information to hide 2 Completed Treatment CNS Hemangioblastoma / Retinal Hemangioblastoma / Von Hippel-Lindau Disease 1 somestatus stop reason just information to hide 2 Completed Treatment Leukemias / Myelodysplastic Syndrome / Myeloproliferative/Myelodysplastic Neoplasm 1 somestatus stop reason just information to hide 2 Completed Treatment Malignant Pleural Mesothelioma (MPM) 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.00179 mg/mL ALOGPS logP 4.5 ALOGPS logP 4.15 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 15.17 Chemaxon pKa (Strongest Basic) 4.95 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 50.7 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 100.98 m3·mol-1 Chemaxon Polarizability 36.52 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.994 Blood Brain Barrier + 0.9829 Caco-2 permeable + 0.6936 P-glycoprotein substrate Non-substrate 0.642 P-glycoprotein inhibitor I Non-inhibitor 0.8083 P-glycoprotein inhibitor II Non-inhibitor 0.8599 Renal organic cation transporter Non-inhibitor 0.6742 CYP450 2C9 substrate Non-substrate 0.8868 CYP450 2D6 substrate Non-substrate 0.8483 CYP450 3A4 substrate Non-substrate 0.6173 CYP450 1A2 substrate Inhibitor 0.9209 CYP450 2C9 inhibitor Inhibitor 0.637 CYP450 2D6 inhibitor Inhibitor 0.5654 CYP450 2C19 inhibitor Inhibitor 0.8432 CYP450 3A4 inhibitor Inhibitor 0.6922 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8539 Ames test AMES toxic 0.5592 Carcinogenicity Non-carcinogens 0.803 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.4258 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7061 hERG inhibition (predictor II) Non-inhibitor 0.8813
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-001i-3927000000-196ba8be28b2e322cff7 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0019000000-6ef94e2bc6482e0ee45d Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-bd5c18660abe18b2a7da Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-5904bcc7619bac424806 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-4f646d487bd073fc1796 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-5797000000-b0ab4fac568ff2814728 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9230000000-6b455f8dfce2c0690381 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 181.48051 predictedDeepCCS 1.0 (2019) [M+H]+ 183.83853 predictedDeepCCS 1.0 (2019) [M+Na]+ 190.89183 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity)
- Specific Function
- actin filament binding
- Gene Name
- EGFR
- Uniprot ID
- P00533
- Uniprot Name
- Epidermal growth factor receptor
- Molecular Weight
- 134276.185 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'
- Specific Function
- ATP binding
- Gene Name
- FLT4
- Uniprot ID
- P35916
- Uniprot Name
- Vascular endothelial growth factor receptor 3
- Molecular Weight
- 152755.94 Da
References
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC
- Specific Function
- ATP binding
- Gene Name
- KDR
- Uniprot ID
- P35968
- Uniprot Name
- Vascular endothelial growth factor receptor 2
- Molecular Weight
- 151525.555 Da
References
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275)
- Specific Function
- ATP binding
- Gene Name
- FLT1
- Uniprot ID
- P17948
- Uniprot Name
- Vascular endothelial growth factor receptor 1
- Molecular Weight
- 150767.185 Da
References
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at October 20, 2007 19:26 / Updated at August 26, 2024 19:23