Dovitinib lactate 是一种多靶点的酪氨酸激酶抑制剂，抑制FLT3，c-Kit，FGFR1/3，VEGFR1/2/3和PDGFRα/β的IC50值分别为 1，2，8/9，10/13/8，27/210 nM。

Dovitinib lactate(TKI258) lactate is a potent inhibitor of fibroblast growth factor receptor 3 (FGFR3) (IC50 :5 nM).

ALL cells were extremely sensitive to TKI258 treatment with a concentration for 50% inhibition of cell proliferation (IC50) values in the nanomolar range in vitro.?By combination with mTOR inhibitor RAD001, a synergistic effect on cell death and cell proliferation was observed in these cells[1].Treatment of SK-HEP1 cells with dovitinib resulted in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration. Dovitinib inhibited basal expression and FGF-induced phosphorylation of FGFR-1, FRS2-α and ERK1/2[2]

In vivo, dovitinib potently inhibited tumor growth of six HCC lines.?Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFR-β/VEGFR-2 signaling pathways.?Dovitinib also caused dephosphorylation of retinoblastoma, upregulation of p-histone H2A-X and p27, and downregulation of p-cdk-2 and cyclin B1, which resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis.?In an orthotopic model, dovitinib potently inhibited primary tumor growth and lung metastasis and significantly prolonged mouse survival[2].

Determination of cell proliferation by 3,[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay.?Different leukemic cells were seeded into a 96-well plate at a density of 5×10^3 cells per well and exposed to different concentrations of TKI258, with or without RAD001, in culture medium.?After incubation for indicated time points.Cell-cycle analysis:For cell-cycle analysis, cells were exposed to different concentrations of TKI258, with or without RAD001, in growth medium.?After different culture durations, cells were harvested and fixed in 70% ethanol at 4°C for over 30 min. After incubation for indicated time points, DNA contents were stained.Apoptosis analysis:Cell apoptosis was detected by determining phosphatidylserine expression on the cell surface[1].

21-0208 and SK-HEP1 cells as well as patient-derived HCC models were employed to study the antitumor effect of dovitinib.?Changes of biomarkers relevant to FGFR/VEGFR/PDGFR pathways were determined by Western blotting.?Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry[1].

692737-80-7

C24H27FN6O4

482.516

CHIR-258 lactate;TKI-258 lactate;多韦替尼乳酸盐

DMSO:30 mg/mL (62.17 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years