Name | Dovitinib lactate |
Synonyms | Unii-69vky8p7ea Dovitinib lactate Dovitinib lactate(TKI258) Dovitinib lactate Monohydrate 4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydr Propanoic acid, 2-hydroxy-, coMpd. with 4-aMino-5-fluoro-3-[6-(4-Methyl-1-piperazinyl)-1H-benziMidazol-2-yl]-2(1H)-quinolinone, hydrate |
CAS | 915769-50-5 |
EINECS | 691-732-5 |
InChI | InChI=1/C21H21FN6O.C3H6O3.H2O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29;1-2(4)3(5)6;/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29);2,4H,1H3,(H,5,6);1H2 |
Molecular Formula | C24H29FN6O5 |
Molar Mass | 500.5226632 |
Storage Condition | 2-8℃ |
In vitro study | Dovitinib potently inhibited the growth of FGF-stimulated B9 cells expressing WT and F384L-FGFR3 with an IC50 of 25 nM. In addition, Dovitinib inhibited the proliferation of B9 cells expressing various activated FGFR3 mutants. Interestingly, very little difference was observed in the sensitivity of the different FGFR3 mutants to Dovitinib, with IC50 ranging from 70 to 90 nM for each of the different mutants. IL-6-dependent B9 cells, containing the vector, were B9-MINV tolerant only to the inhibitory activity of Dovitinib at concentrations up to 1 μm. Dovitinib inhibited the proliferation of KMS11 (FGFR3-Y373C),OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells with IC50 of 90 nM (KMS11 and OPM2) and 550 nM, respectively. In primordial MM cells expressing FGFR3, Dovitinib inhibits FGF-mediated ERK1/2 phosphorylation and induces cytotoxicity. Cells treated with 500 nM Dovitinib, cultured with BMSCs with a certain degree of tolerance, showed 44.6% growth inhibition compared to medium without BMSCs, the cells exhibited a growth inhibition of 71.6%. Dovitinib inhibits the proliferation of M-NFS-60, a M-CSF growth-driven mouse myeloblast cell line, at a median effective concentration (EC50) of 220 nM. Treatment of SK-HEP1 cells with Dovitinib resulted in a dose-dependent decrease in cell number, and a G2/M phase arrest, a decrease in G0/G1 and S phases, Anchorage-independent growth inhibition, and a bFGF-induced block of cell motility. The IC50 of Dovitinib in SK-HEP1 cells is about 1.7 μm. In SK-HEP1 and 21-0208 cells, Dovitinib also significantly reduced basal phosphorylation levels of FGFR-1,FGFR substrate 2α (FRS2-α), and ERK1/2, without affecting Akt. In 21-0208 HCC cells, Dovitinib significantly inhibited bFGF-induced phosphorylation of FGFR-1,FRS2-α,ERK1/2, but did not affect Akt. |
In vivo study | Dovitinib induces cytostatic and cytotoxic responses in vivo, leading to regression of tumor cells expressing fgfr3. Dovitinib exhibited dose-and exposure-dependent inhibition of tumor xenografts expressing target receptor tyrosine kinases (RTKs). Dovitinib effectively inhibited tumor growth in six HCC lines. Inhibition of angiogenesis is associated with inactivation of the FGFR/PDGFRβ/VEGFR2 signaling pathway. In The orthotopic inoculation model, Dovitinib effectively inhibited primary tumor growth and lung metastasis, and significantly prolonged the survival time of mice. Administration of Dovitinib resulted in significant tumor growth inhibition and tumor regression, including most established tumors (500-1,000mm |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.072 ml | 10.362 ml | 20.725 ml |
5 mM | 0.414 ml | 2.072 ml | 4.145 ml |
10 mM | 0.207 ml | 1.036 ml | 2.072 ml |
5 mM | 0.041 ml | 0.207 ml | 0.414 ml |