Description
Dovitinib (TKI-258) can inhibit VEGFR1, VEGFR2, VEGFR3, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR3, Flt3, and c-Kit with IC50 of 10 nM, 13 nM, 8 nM, 210 nM, 27 nM, 8 nM, 9 nM, 1 nM and 2 nM.
Storage
2 years at -20centigrade Powder
Targets
VEGFR1/VEGFR2/VEGFR3, PDGFR-alpha/PDGFR-beta, FGFR1/FGFR3, Flt3, c-Kit
Molecular Formula
C21H21FN6O
Chemical Name
1-amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one
Solubility
DMSO 30 mg/mL Water
In vitro
As an inhibitor of class III, IV, and V RTKs, Dovitinib (TKI258, CHIR258) can potently inhibit FGFR3 with IC50 (an inhibitory concentration of 50%) of 5 nM in in vitro kinase assays. Dovitinib (TKI258, CHIR258) also inhibits vascular endothelial growth factor receptor 1/2, fibroblast growth factor receptor 1/3, Fms-like tyrosine kinase 3 (FLT3), and platelet-derived growth factor receptor beta (PDGFRbeta).
In vivo
Dovitinib (TKI258, CHIR258) shows both antitumor and antiangiogenic activities in vivo.Dovitinib (TKI258, CHIR258) selectively inhibit the growth of B9 cells and human myeloma cell lines expressing wild-type (WT) or activated mutant FGFR3 by inducing cytostatic and cytotoxic effects in those responsive cell lines. In vivo administration of CHIR-258 resulted in significant tumor growth inhibition and tumor regressions by reducing phosphorylated PDGFRbeta and phosphorylated ERK. In some primary myeloma cells, Dovitinib (TKI258, CHIR258) inhibited downstream extracellular signal-regulated kinase (ERK) 1/2 phosphorylation with an associated cytotoxic response. Treatment of KM12L4a human colon cancer cells with Dovitinib (TKI258, CHIR258) resulted in a dose-dependent inhibition of vascular endothelial growth factor receptor 1 and PDGFRbeta phosphorylation and reduction of phosphorylated extracellular signal-regulated kinase (ERK) levels. Therapeutic efficacy of CHIR-258 was demonstrated in a xenograft mouse model of FGFR3 MM.
Download Datasheet