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Vatalanib (PTK787) 2HCl

Name: Vatalanib (PTK787) 2HCl
Brand: Selleck Chemicals
SKU: S1101
Rating: 5 (43 reviews)

Catalog No.S1101 Synonyms: ZK 222584 (cpg-79787) 2HCl

For research use only.

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 Chemical Structure

CAS No. 212141-51-0

Selleck's Vatalanib (PTK787) 2HCl has been cited by 43 publications

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VEGFR Signaling Pathway Map

Biological Activity

Description

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.

Targets

VEGFR2/KDR ^[1] (Cell-free assay)	VEGFR1/FLT1 ^[1] (Cell-free assay)	VEGFR2/Flk1 ^[1] (Cell-free assay)	PDGFRβ ^[1] (Cell-free assay)	VEGFR3/FLT4 ^[1] (Cell-free assay)	Click to View More Targets
37 nM	77 nM	270 nM	580 nM	660 nM	Click to View More Targets

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]

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]

Protocol (from reference)

Kinase Assay:^[1]	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.
Cell Research:^[1]	Cell lines: HUVECs Concentrations: 0-10 μM Incubation Time: 48 hours Method: As a test of the ability of PTK787/ZK 222584 to inhibit a functional response to VEGF, an endothelial cell proliferation assay, based on BrdUrd incorporation is used. Subconfluent HUVECs are seeded into 96-well plates coated with 1.5% gelatin and then incubated at 37 °C and 5% CO₂ in growth medium. After 24 hours, growth medium is replaced by basal medium containing 1.5% FCS and a constant concentration of VEGF (50 ng/mL), bFGF (0.5 ng/mL), or FCS (5%), in the presence or absence of PTK787/ZK 222584. As a control, wells without growth factor are also included. After 24 hours of incubation, BrdUrd labeling solution is added, and cells incubated an additional 24 hours before fixation, blocking, and addition of peroxidase-labeled anti-BrdUrd antibody. Bound antibody is then detected using 3,3′5,5′-tetramethylbenzidine substrate, which results in a colored reaction product that is quantified spectrophotometrically at 450 nm.
Animal Research:^[1]	Animal Models: A431 epithelial carcinoma, Ls174T colon carcinoma, HT-29 colon carcinoma, PC-3 prostate carcinoma, DU145 prostate carcinoma, and CWR-22 prostate carcinoma cells are injected s.c. into the nude mice. Dosages: 25-100 mg/kg Administration: Administered via p.o.

References

Solubility (25°C)

In vitro	DMSO	85 mg/mL warmed (202.51 mM)
	Water	10 mg/mL (23.82 mM)
	Ethanol	'6 mg/mL

Chemical Information

Molecular Weight	419.73
Formula	C₂₀H₁₅ClN₄.2HCl
CAS No.	212141-51-0
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1=CC=C2C(=C1)C(=NN=C2NC3=CC=C(C=C3)Cl)CC4=CC=NC=C4.Cl.Cl

Download Vatalanib (PTK787) 2HCl SDF

In vivo Formulation Calculator (Clear solution)

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00348790	Completed	Drug: vatalanib	Brain and Central Nervous System Tumors\|Sarcoma	Northwestern University\|Novartis	May 2006	Phase 2
NCT00358163	Unknown status	Drug: PTK787/ZK 222584\|Drug: paclitaxel	Metastatic Non-hematologic Malignancies	Massachusetts General Hospital\|Novartis Pharmaceuticals\|Beth Israel Deaconess Medical Center\|Brigham and Women''s Hospital\|Dana-Farber Cancer Institute	April 2006	Phase 1
NCT00263198	Terminated	Drug: PTK787/ZK222584\|Drug: Letrozole	Breast Neoplasms	Washington University School of Medicine\|Novartis	March 2006	Phase 2
NCT00281125	Terminated	Drug: PTK787 and Pemetrexed with or without Cisplatin	Non-Small Cell Lung Cancer and Pleural Mesothelioma	Nevada Cancer Institute	January 2006	Phase 1\|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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