Description
Vatalanib dihydrochloride (PTK787, ZK 222584) can inhibit VEGFR-2 (KDR), VEGF-R1(FLT-1), Flk and c-Kit with IC50 of 37 nM, 77 nM, 270 nM and 730 nM.
Storage
2 years at -20 centigrade
Targets
VEGFR2(KDR), VEGF-R1(FLT-1), Flk, c-Kit
Molecular Formula
C20H15ClN4?2HCl
Chemical Name
N-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine dihydrochloride
Solubility
DSMO 85 mg/mL Water 10 mg/mL Ethanol 6 mg/mL
In vitro
Vatalanib dihydrochloride (PTK787, ZK 222584) can inhibit VEGFR-2 (KDR), VEGF-R1(FLT-1), Flk and c-Kit with IC50 of 37 nM, 77 nM, 270 nM and 730 nM. PTK787 (ZK 222584) inhibits VEGF-induced autophosphorylation of kinase insert domain-containing receptor (KDR), endothelial cell proliferation, migration, and survival. PTK787/ZK 222584 induces dose-dependent inhibition of VEGF and PDGF-induced angiogenesis in a growth factor implant model, as well as a tumor cell-driven angiogenesis.
In vivo
(1) Renal cell carcinoma (RCC) As a specific inhibitor of both VEGF-receptor tyrosine kinases, PTK787/ZK 222584 potently inhibits tumor growth, metastases formation, and tumor vascularization in murine renal cell carcinoma. (2) MM cell lines PTK787 acts both directly on MM cells and in the bone marrow microenvironment. Specifically, PTK787 (1-5 micro M) inhibits proliferation of MM cells by 50%. This effect of PTK787 is dose dependent in both MM cell lines. PTK787 enhances the inhibitory effect of dexamethasone on growth of MM cells and can overcome the protective effect of interleukin 6 (IL-6) against dexamethasone-induced apoptosis. PTK787 (1 micro M) also blocks VEGF-induced migration of MM cells across an extracellular matrix. Importantly, PTK787 also inhibits the increased MM cell proliferation and increased IL-6 and VEGF secretion in cultures of MM cells adherent to bone marrow stem cells. (3) Malignant glioma cell lines Early and delayed application of PTK787 (ZK222584) in V(+) glioma-bearing animals resulted in a significant reduction of tumor size (71% and 36%, P (4) Models of rheumatoid arthritis PTK787 (ZK222584) treatment caused dose dependent reduction in the vascularity of the granulomatous air pouch model. PTK787 (ZK222584) inhibited knee swelling by 40% in antigen-induced arthritis.
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