Home Protein Tyrosine Kinase VEGFR inhibitor Vatalanib (PTK787) 2HCl

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Vatalanib (PTK787) 2HCl VEGFR inhibitor

Cat.No.S1101

Vatalanib 2HCl (PTK787, ZK 222584, cpg-79787) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM in a cell-free assay, less potent against VEGFR1/Flt-1, 18-fold against VEGFR3/Flt-4. Phase 3.
Vatalanib (PTK787) 2HCl VEGFR inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 419.73

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Quality Control

Chemical Information, Storage & Stability

Molecular Weight 419.73 Formula

C20H15ClN4.2HCl

 Storage (From the date of receipt)
CAS No. 212141-51-0 Download SDF Storage of Stock Solutions

Synonyms ZK 222584 (cpg-79787) 2HCl Smiles C1=CC=C2C(=C1)C(=NN=C2NC3=CC=C(C=C3)Cl)CC4=CC=NC=C4.Cl.Cl

Solubility

In vitro
Batch:

DMSO : 21.25 mg/mL ( (50.62 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 10 mg/mL

Ethanol : 6 mg/mL

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
VEGFR2/KDR [1]
(Cell-free assay)
37 nM
VEGFR1/FLT1 [1]
(Cell-free assay)
77 nM
VEGFR2/Flk1 [1]
(Cell-free assay)
270 nM
PDGFRβ [1]
(Cell-free assay)
580 nM
VEGFR3/FLT4 [1]
(Cell-free assay)
660 nM
c-Kit [1]
(Cell-free assay)
730 nM
c-Fms [1]
(Cell-free assay)
1.4 μM
In vitro
Vatalanib also inhibits Flk, c-Kit and PDGFRβ with IC50 of 270 nM, 730 nM and 580 nM, respectively. Furthermore, Vatalanib shows the anti-proliferation effect by inhibiting thymidine incorporation induced by VEGF in HUVECs with and IC50 of 7.1 nM, and dose-dependently suppresses VEGF-induced survival and migration of endothelial cells in the same dose range without cytotoxic or antiproliferative effect on cells that do not express VEGF receptors. [1] A recent study shows that Vatalanib significantly inhibits the growth of hepatocellular carcinoma cells and enhances the IFN/5-FU induced apoptosis by increasing proteins levels of Bax and reduced Bcl-xL and Bcl-2. [2]
Kinase Assay
VEGF Receptor Tyrosine Kinase Assays
The in vitro kinase assays are performed in 96-well plates as a filter binding assay, using the recombinant GST-fused kinase domains expressed in baculovirus and purified over glutathione-Sepharose. γ-[33P]ATP is used as the phosphate donor, and poly-(Glu:Tyr 4:1) peptide is used as the acceptor. Recombinant GST-fusion proteins are diluted in 20 mM Tris·HCl (pH 7.5) containing 1–3 mM MnCl2, 3–10 mM MgCl2, 0.25 mg/mL polyethylene glycol 20000, and 1 mM DTT, according to their specific activity. Each GST-fused kinase is incubated under optimized buffer conditions [20 mM Tris-HCl buffer (pH 7.5), 1–3 mM MnCl2, 3–10 mM MgCl2, 3–8 μg/mL poly-(Glu:Tyr 4:1), 0.25 mg/mL polyethylene glycol 20000, 8 μM ATP, 10 μM sodium vanadate, 1 mM DTT, and 0.2 μCi[γ-33P]ATP in a total volume of 30 μL in the presence or absence of a test substance for 10 minutes at ambient temperature. The reaction is stopped by adding 10 μL of 250 mM EDTA. Using a 96-well filter system, half the volume (20 μL) is transferred onto a Immobilon-polyvinylidene difluoride membrane. The membrane is then washed extensively in 0.5% H3PO4 and then soaked in ethanol. After drying, Microscint cocktail is added, and scintillation counting is performed. IC50s for PTK787/ZK 222584 or SU5416 in these as well as all assays described below are calculated by linear regression analysis of the percentage inhibition.
In vivo
Vatalanib induces dose-dependent inhibition of the angiogenic response to VEGF and PDGF in both a growth factor implant model and a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, Vatalanib also inhibits the growth and metastasesof several human carcinomas in nude mice without significant effect on circulating blood cells or bone marrow leukocytes. [1]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00348790 Completed
Brain and Central Nervous System Tumors|Sarcoma
Northwestern University|Novartis
 May 2006 Phase 2
NCT00358163 Terminated
Metastatic Non-hematologic Malignancies
Dana-Farber Cancer Institute|Novartis Pharmaceuticals|Beth Israel Deaconess Medical Center|Brigham and Women''s Hospital|Massachusetts General Hospital
 April 26 2006 Phase 1
NCT00263198 Terminated
Breast Neoplasms
Washington University School of Medicine|Novartis
 March 2006 Phase 2
NCT00281125 Terminated
Non-Small Cell Lung Cancer and Pleural Mesothelioma
Nevada Cancer Institute
 January 2006 Phase 1|Phase 2

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