Vatalanib (PTK787) 2HCl

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.

N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine dihydrochloride

0-10 uM

25-100 mg/kg

37 nM, 37 nM, 37 nM, 37 nM, 37 nM, 37 nM

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]

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. gamma-[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 ug/mL poly-(Glu:Tyr 4:1), 0.25 mg/mL polyethylene glycol 20000, 8 uM ATP, 10 uM sodium vanadate, 1 mM DTT, and 0.2 uCi[gamma-33P]ATP in a total volume of 30 uL in the presence or absence of a test substance for 10 minutes at ambient temperature. The reaction is stopped by adding 10 uL of 250 mM EDTA. Using a 96-well filter system, hame (20 uL) 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.

419, 73

Data from [Cell Res, 2011, 21, 1080-1087], Vatalanib 2HCl (PTK787)purchased from Selleck, Combinational treatment of kinase inhibitors induces the similar phenotype produced by PP1. All images are lateral view with dorsal to the top and anterior to the left. The combinational treatment of Dasatinib (D) or U0126 (U) with Sunitinib (SU), PTK787 (PTK), or ZM323881 (Z) resulted in the shrinkage of dorsal aorta.

DMSO 85 mg/mL, Water 10 mg/mL, Ethanol 6 mg/mL