Vatalanib (PTK787) 2HCl

Catalog No.S1101 Batch:S110102

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Technical Data

Formula

C20H15ClN4.2HCl
Molecular Weight 419.73 CAS No. 212141-51-0
Solubility (25°C)* In vitro DMSO 85 mg/mL (202.51 mM)
Water 10 mg/mL (23.82 mM)
Ethanol 6 mg/mL (14.29 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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)		 View More
37 nM 77 nM 270 nM 580 nM 660 nM
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 Assay:[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 Study:[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.

Customer Product Validation

Data from [Data independently produced by Development, 2013, 140, 4323-34]

Data from [Cell Res, 2011, 21, 1080-1087]

Data from [Circ Res, 2011, 108, 1190-1198]

Selleck's Vatalanib (PTK787) 2HCl has been cited by 51 publications

Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma [ J Exp Clin Cancer Res, 2023, 42(1):79] PubMed: 37013646
Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma [ Cancer Med, 2023, 12(15):16416-16430] PubMed: 37341071
Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma [ Cancer Med, 2023, 12(15):16416-16430] PubMed: 37341071
Investigation of the pharmacological effect and mechanism of mountain-cultivated ginseng and garden ginseng in cardiovascular diseases based on network pharmacology and zebrafish experiments [ Front Pharmacol, 2022, 13:920979] PubMed: 36120313
In Vitro Angiogenesis Inhibition and Endothelial Cell Growth and Morphology [ Int J Mol Sci, 2022, 23(8)4277] PubMed: 35457095
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258] PubMed: 35207746
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li-Fraumeni syndrome [ Hum Cell, 2022, 10.1007/s13577-022-00671-y] PubMed: 35118583
Prognostic Analysis of LncRNA MCM3AP-AS1 in Colorectal Cancer and the Mechanism of Its Effect on Tumor Cell Activity [ Biomed Res Int, 2022, 2022:1616370] PubMed: 36172487
Rational application of gefitinib in NSCLC patients with sensitive EGFR mutations based on pharmacokinetics and metabolomics [ Acta Pharmacol Sin, 2021, 10.1038/s41401-021-00791-5] PubMed: 34737420
Establishment and characterization of novel patient-derived cell lines from giant cell tumor of bone [ Hum Cell, 2021, 10.1007/s13577-021-00579-z] PubMed: 34304386

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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