Dovitinib (TKI-258, CHIR-258)

Catalog No.S1018

Dovitinib (TKI-258, CHIR-258) Chemical Structure

Molecular Weight(MW): 392.43

Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.

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In DMSO USD 191 In stock
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7 Customer Reviews

  • In vitro assays on CUX1-FGFR1-expressing Ba/F3 cells. a. IL-3 deprivation of Ba/F3 cells transduced with CUX1-FGFR1 resulted in transformation to growth factor independent growth. The mean growth ±SEM of three separate measurements over four consecutive days is presented. b. The dose-response curves of CUX1-FGFR1-transduced Ba/F3 cells, treated with TKI258 and PKC412 for 48 hours in the absence or presence of IL-3 (2 ng/ml) are presented. Points represent the average results of two experiments done in triplicate plotted with the curve-fitting GraphPad Prism 5 software; bars, SD. The calculated IC50 for each inhibitor is indicated. c. Western blot analyses of CUX1-FGFR1-transformed Ba/F3 cells after treatment with PKC412 and TKI258. Phosphorylation of CUX1-FGFR1 and its downstream effectors STAT5 and RPS6K decreased with increasing inhibitor concentrations. Expression of total CUX1-FGFR1, STAT5 and RPS6K remained unaffected. d. Effect of PKC412 and TKI258 on apoptosis of CUX1-FGFR1-expressing Ba/F3 cells after treatment for 48 hours. The percentage of apoptotic plus necrotic CUX1-FGFR1-transduced Ba/F3 cells is indicated.

    haematologica 2011 96, 922-926. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

    RT112 cells were exposed to PD173074 (PD) (500 nM) for 0-24 h, TKI-258 (TK) (500 nM) or SU5402 (SU) (5 nM) for 1 h. Cells were lysed, FGFR3 was immunoprecipitated (immunoprecipitated, IP) and blots (immunoblot, IB) were probed for phospho-tyrosine and reprobed for FGFR3 or probed for phospho-ERK and reprobed for total ERK.

    Brit J Cancer 2010 104, 75-82. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Cells were exposed to PD173074 or TKI-258 (500 nM) for 24 h. Cell cycle profile was analysed using the Guava Easycyte Plus flow cytometry system.

    Brit J Cancer 2010 104, 75-82. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

     

    Orthotopic xenografts of HNSCC cell lines (A) SCC-1 and (B) OSC-19 were treated with dovitinib (20 mg/kg/day). In addition, the OSC-19 xenografts were treated with +/ radiation therapy. Marker, mean for triplicate; bars, SE. Statistical significance by unpaired t-test, p < 0.05.

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Treatments were initiated at time of orthotopic implantation. Growth stabilization was seen by day 8 of treatment (Fig. B). On day 17, tumors were har-vested and histological analysis was performed (Fig. C). Following Ki67 staining, tumors from control xenografts were found to have a higher percentage of proliferating cells (62%) compared to those treated with dovitinib (14%; p = 0.005). The incidence of lymph nodes metastasis was greater in the control cohort ( n = 15) com-pared to those treated with dovitinib (n = 5).

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

    Dose–response curves for HNSCC cells and fibroblasts treated in vitro with dovitinib (0–1000 nM). Boxes, mean for triplicate; bars, SE

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Ba/F3 cell lines expressing the recombinant TEL/kinase domain fusion protein for FGFR1-4 .Cells were grown in RPMI 1640 containing 10% FBS and 500 ng/mL puromycin. The parental Ba/F3 cell line transduced with an empty vector was grown in 10 ng/mL IL-3 (R & D systems). Cell viability was assessed at 72 hours using the Cell Titer 96 Aqueous One Solution (Promega). Data were plotted as percent viability relative to vehicle-treated cells and are shown as mean (±SD) from 3 experiments.

    AACR 2011 Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

Purity & Quality Control

Choose Selective FLT3 Inhibitors

Biological Activity

Description Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.
Targets
FLT3 [1]
(Cell-free assay)
c-Kit [1]
(Cell-free assay)
FGFR1 [1]
(Cell-free assay)
VEGFR3/FLT4 [1]
(Cell-free assay)
FGFR3 [1]
(Cell-free assay)
1 nM 2 nM 8 nM 8 nM 9 nM
In vitro

Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 of 25 nM. In addition, Dovitinib inhibits proliferation of B9 cells expressing each of the various activated mutants of FGFR3. Interestingly, there are minimal observed differences in the sensitivity of the different FGFR3 mutations to Dovitinib, with the IC50 ranging from 70 to 90 nM for each of the various mutations. IL-6-dependent B9 cells containing vector only (B9-MINV cells are resistant to the inhibitory activity of Dovitinib at concentrations up to 1 μM. Dovitinib inhibits cell 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. Dovitinib inhibits FGF-mediated ERK1/2 phosphorylation and induces cytotoxicity in FGFR3-expressing primary MM cells. BMSCs does confer a modest degree of resistance with 44.6% growth inhibition for cells treated with 500 nM Dovitinib and cultured on stroma compared with 71.6% growth inhibition for cells grown without BMSCs. Dovitinib inhibits proliferation of M-NFS-60, an M-CSF growth-driven mouse myeloblastic cell line with a median effective concentration (EC50) of 220 nM. [1] Treatment of SK-HEP1 cells with Dovitinib results in a dose-dependent reduction in cell number and G2/M phase arrest with reduction in the G0/G1 and S phases, inhibition of anchorage-independent growth and blockage of bFGF-induced cell motility. The IC50 for Dovitinib in SK-HEP1 cells is approximately 1.7 μM. Dovitinib also significantly reduces the basal phosphorylation levels of FGFR-1, FGFR substrate 2α (FRS2-α) and ERK1/2 but not Akt in both SK-HEP1 and 21-0208 cells. In 21-0208 HCC cells, Dovitinib significantly inhibits bFGF-induced phosphorylation of FGFR-1, FRS2-α, ERK1/2 but not Akt. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SupB15 MlPqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTBwNES5JO69VQ>? MVKyOVIxOjB5Mx?=
SupB15-R NYTKUWZvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTBwNUW4JO69VQ>? NFnSc5czPTJyMkC3Ny=>
BaF3-pSRα MoK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{\qVGlEPTB;MD62Olgh|ryP NETIRZczPTJyMkC3Ny=>
BaF3-p210Bcr-Abl M2ruWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWC1fFUyUUN3ME2wMlY6OiEQvF2= NV3NT4pSOjV{MEKwO|M>
BaF3-p210Bcr-Abl-T315I MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoO3TWM2OD1{Lk[yOkDPxE1? NUn5cVB6OjV{MEKwO|M>
CCRF-CEM MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDx[4pKSzVyPUCuN|k5KM7:TR?= MVGyOVIxOjB5Mh?=
CEM/C2 M4TMfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmrYTWM2OD1zLkGyOUDPxE1? NWTMWItIOjV{MEKwO|I>
Nalm-6 NV;D[2kzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm\QTWM2OD1yLkO4NkDPxE1? NInZc4UzPTJyMkC3Ni=>
SEM-K2 NX\pS2hDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVe0Rm5HUUN3ME2wMlAzOiEQvF2= MoS1NlUzODJyN{K=
HB-1119 MnvKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV[5coR{UUN3ME2wMlAzQCEQvF2= MlnQNlUzODJyN{K=
RS4:11 M{Xy[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4[xZ2lEPTB;Mj64NUDPxE1? NIDFcZIzPTJyMkC3Ni=>
Nalm-6 MVfBdI9xfG:|aYOgRZN{[Xl? M1HIe|Ih|ryP M2npclI1NzR6IHi= NVnQOWVScW6mdXPld{BieG:ydH;zbZMhemW|dXz0bY5oKGmwIHHic5V1KDd{JTDv[kBk\WyuIHTlZZRpKGGodHXyJFI1KGhidILlZZRu\W62IHHu[EA5OSViYX\0[ZIhPDhiaB?= M2i0VlI2OjB{MEey
SEM-K2 MX3BdI9xfG:|aYOgRZN{[Xl? M{TQV|AvOS9zIN88US=> NXrIZnE4OjRiaB?= M1rLRolv\HWlZYOg[YFzdHliYYDvdJRwe2m|IH;mJHNGVS2NMjDj[YxteyCjdDCwMlEh|ryPIHHmeIVzKDJ2IHi= MV:yOVIxOjB5Mh?=
HCT-116 M2\YWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX2w[JZzUUN3ME2zMlA2OC53ODFOwG0> M3\JTlI1PDl3N{Ww
HT-29 NWTORnB6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnBc21KSzVyPUWuNlEvQTNizszN NFP2UZIzPDR7NUe1NC=>
SW-480 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfvTWM2OD12LkOzNE41PyEQvF2= Mm\mNlQ1QTV5NUC=
CaCO2 NV;LdoJ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7UVGJKSzVyPUOuNlMxNjZ2IN88US=> M3rHOFI1PDl3N{Ww
LS174T MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGXTdpRKSzVyPUSuN|MxNjR5IN88US=> NVPPcm1ZOjR2OUW3OVA>
HEC-1A NGDlUmlHfW6ldHnvckBCe3OjeR?= NWj4bVhCOC5yNT:wMlEwOC53IN88US=> MnKwO|IhcA>? M1L4VYNifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v M1XmXVI1PDl3N{Ww
AN3CA NV\peIhGTnWwY4Tpc44hSXO|YYm= NYfCTY9jOC5yNT:wMlEwOC53IN88US=> MoC4O|IhcA>? NE\KTXNk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? NHvJd3QzPDR7NUe1NC=>
MFE-296  MmDxSpVv[3Srb36gRZN{[Xl? MUewMlA2NzBwMT:wMlUh|ryP NFzQZY84OiCq MX7jZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> MXiyOFQ6PTd3MB?=
UMC3 MkXHR4VtdCCYaXHibYxqfHliQYPzZZk> NUW1NpFrOS1zMDFOwG0> MlHCO|IhcA>? NIXXdYpqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NY[wTmIyOjR|MkW0OlE>
5637 MkXwR4VtdCCYaXHibYxqfHliQYPzZZk> NWPGbWpPOS1zMDFOwG0> NX7tdHZ[PzJiaB?= MWDpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MkX4NlQ{OjV2NkG=
HU456 M4TSSWNmdGxiVnnhZoltcXS7IFHzd4F6 NVnJ[|h4OS1zMDFOwG0> NFnVUFM4OiCq M36zNYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MV6yOFMzPTR4MR?=
MGHU4 NIryZ|BE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MmL1NU0yOCEQvF2= M4jFT|czKGh? NHqwWoNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MWWyOFMzPTR4MR?=
HT1376 NUXic4RXS2WubDDWbYFjcWyrdImgRZN{[Xl? MmLJNU0yOCEQvF2= M2jScFczKGh? NUDEfYxNcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M1vUPFI1OzJ3NE[x
RT112 NFO5RZNE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NXnhflBbOS1zMDFOwG0> M{XyTlczKGh? NF7ZboNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MYWyOFMzPTR4MR?=
T24 NULCeWR{S2WubDDWbYFjcWyrdImgRZN{[Xl? M3q0U|EuOTBizszN MXi3NkBp NXPyR2hRcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{mzUVI1OzJ3NE[x
BFTC905 NHHhUoRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NHXGNIMyNTFyIN88US=> MVy3NkBp NEPSSYRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NYX3OXo1OjR|MkW0OlE>
TCC-SUP MnfnR4VtdCCYaXHibYxqfHliQYPzZZk> M{PJWlEuOTBizszN MXu3NkBp MoD3bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NI\BWHEzPDN{NUS2NS=>
RT4 MUPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NGPRSGgyNTFyIN88US=> NVfPN|d1PzJiaB?= MmeybY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NUiyPYF5OjR|MkW0OlE>
HONE1 NYi3RYc2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHr4W3YxNjFvMUCg{txO NI\WOZc1QMLiaB?= M3;rRYlv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NGHwXIwzPDJ|OEC5OC=>
HNE1 M2TjeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXeyNlI1OC5zLUGwJO69VQ>? MmnyOFjDqGh? MUDpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MVqyOFI{QDB7NB?=
CNE2  M4rMZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3GxNVAvOS1zMDFOwG0> NE\mN|A1QMLiaB?= M2HVSolv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MXmyOFI{QDB7NB?=
C666-1 NWWwRox1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHDfGNoOC5zLUGwJO69VQ>? MVm0POKhcA>? MVnpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MnLjNlQzOzhyOUS=
HeLa Mli3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE\FfIcxNjFvMUCg{txO NILvRXozPCCq M170colv\HWlZYOgS|IwVSCjcoLld5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> Ml;DNlQzOzhyOUS=
Hep3B NH[0bXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYDGR4lZOC5zLUGwJO69VQ>? M1jmclI1KGh? MmLhbY5lfWOnczDHNuKh[XK{ZYP0xsA> NYXKe29vOjR{M{iwPVQ>
HepG2 NYrOSmxGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\qPFQ5KGh? NUfK[3JQUUN3ME2yMlczPyEEsTCwMlQzQSEQvF2= MoDVNlM2PDZ3OUG=
Hep3B M2LFXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoDCOFghcA>? NXHIUIVoUUN3ME20MlIzOyEEsTCwMlg{QSEQvF2= MYmyN|U1PjV7MR?=
PLC/PRF5 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmm1OFghcA>? MV\JR|UxRTF4LkGyNEDDuSB2LkCwNUDPxE1? NV;tO3FsOjN3NE[1PVE>
Huh7 M4LjOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHTFbHI1QCCq MWDJR|UxRTF3LkCwO{DDuSB5LkOzOEDPxE1? MmfMNlM2PDZ3OUG=
HepG2 NX\nUZAxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1y5N|czKGh? MUnJR|UxRTFwMkCwJOKyKDBwMkK2JO69VQ>? MoX0NlM2PDZ3OUG=
Hep3B MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{\CWlczKGh? NIDLeHNKSzVyPUCuPFkzKMLzIECuNFQ1KM7:TR?= M4DGSlI{PTR4NUmx
PLC/PRF5 MlS1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWm3NkBp NF60SIlKSzVyPUOuNVExKMLzIECuN|M4KM7:TR?= M3;Tb|I{PTR4NUmx
Huh7 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDIO|IhcA>? NF\GbJZKSzVyPUOuPVgxKMLzIECuPFA{KM7:TR?= M3TqWFI{PTR4NUmx
MFE280 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnrkTWM2OD1yLkSyJOKyKDBwME[g{txO MUCyN|Q1OzhyNR?=
AN3CA NITMcXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTBwNUCgxtEhOC5zMDFOwG0> M2r0TVI{PDR|OEC1
HEC155 NIf5XHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrMTWM2OD1yLk[2JOKyKDBwMEmg{txO NVvvN4tCOjN2NEO4NFU>
MFE296 M2TuUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTBwNk[gxtEhOC5zOTFOwG0> MlHHNlM1PDN6MEW=
SPAC1S MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGHCXXVKSzVyPUCuO|chyrFiMD6wPEDPxE1? NFnKWnUzOzR2M{iwOS=>
RL952 M3Gycmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MULJR|UxRTBwOUOgxtEhOC5yMTFOwG0> NI\QVmgzOzR2M{iwOS=>
EN1 M{TvcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlzwTWM2OD1zLkCyJOKyKDBwMkWg{txO NFfTW40zOzR2M{iwOS=>
SNGII MnjmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zofmlEPTB;MT6yOEDDuSByLkK4JO69VQ>? NVXXNXd6OjN2NEO4NFU>
ISHIKAWA MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml;CTWM2OD1zLkOwJOKyKDBwMUGg{txO NEfPfXczOzR2M{iwOS=>
HEC1A NWTUNHg{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFrqVYlKSzVyPUGuN|QhyrFiMD6zNEDPxE1? NUHrdo01OjN2NEO4NFU>
KLE NEPYWplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{[xPWlEPTB;MT6zO{DDuSByLkCyJO69VQ>? M3GyUFI{PDR|OEC1
SNGM MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEn4OmxKSzVyPUGuOFIhyrFiMD6xN{DPxE1? MVqyN|Q1OzhyNR?=
USPC2 M{ToW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPPe2RKSzVyPUGuOlIhyrFiMD6wNUDPxE1? NGj1[nAzOzR2M{iwOS=>
EN MoXrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXfJR|UxRTFwNk[gxtEhOC5yMTFOwG0> MWmyN|Q1OzhyNR?=
MFE319 M{XJdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlOzTWM2OD1zLki3JOKyKDBwNEWg{txO MmTwNlM1PDN6MEW=
EFE184 NIXMW3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUfJR|UxRTJwMESgxtEhOC5zMzFOwG0> MkPZNlM1PDN6MEW=
ECC1 M{DvOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFnoUZVKSzVyPUKuNFchyrFiMD6wNUDPxE1? M2jY[|I{PDR|OEC1
HEC1B Ml7zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTJwNUegxtEhOC5{MzFOwG0> MYCyN|Q1OzhyNR?=
USPC1 Moi1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjuTWM2OD1{Lk[wJOKyKDBwMUOg{txO M{fCT|I{PDR|OEC1
SPAC1L M1vZ[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVPJR|UxRTNwME[gxtEhOS5zNDFOwG0> NGXMXVgzOzR2M{iwOS=>
HUVEC NWG4TFFNS2WubDDWbYFjcWyrdImgRZN{[Xl? MX[wMVI2KM7:TR?= MWq3NkBp NWLM[Gc1TE2VTx?= NU\qfWFvcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NY\oNnBlOjN{MkiwNVc>
HMVEC MnTBR4VtdCCYaXHibYxqfHliQYPzZZk> Mn34NE0zPSEQvF2= MV63NkBp MXnEUXNQ MU\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NV3mdFV6OjN{MkiwNVc>
MHCC-97H NEX2[YVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MmXqNE0zPSEQvF2= M{fhRVczKGh? MnX6SG1UVw>? M4LKXIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NWDPR4JPOjN{MkiwNVc>
SMMC7721 Ml\ER4VtdCCYaXHibYxqfHliQYPzZZk> NXu5dG9XOC1{NTFOwG0> M1nP[lczKGh? MVPEUXNQ MXTpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MnzENlMzOjhyMUe=
Huh-7 NHzhcFlCeG:ydH;zbZMhSXO|YYm= M3W1flAuOTJwNTFOwG0> MmLPNlQhcA>? NVPaWZU2TE2VT9Mg MUfz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MljkNlIzOzB2N{m=
Sk-Hep1 M4LueGFxd3C2b4Ppd{BCe3OjeR?= NInid|ExNTF{LkWg{txO NHvU[G8zPCCq Ml\QSG1UV8Li MWrz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M3rtclIzOjNyNEe5
Hep3B M1:z[2Fxd3C2b4Ppd{BCe3OjeR?= NGfxXosxNTF{LkWg{txO M2HqXVI1KGh? MmThSG1UV8Li M4OyTZNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NYjFXIxiOjJ{M{C0O|k>
PLC5 MnLYRZBweHSxc3nzJGF{e2G7 MUiwMVEzNjVizszN MYeyOEBp NUWyXZdHTE2VT9Mg Ml7Sd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> MknvNlIzOzB2N{m=
PLC5 Mn2wR4VtdCCYaXHibYxqfHliQYPzZZk> NVfJWJduOC1zNTFOwG0> MoHyO|IhcA>? M1yyPZJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= M3HiPFIzOThyM{C4
Hep3B NH;mSJZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? Ml3UNE0yPSEQvF2= MnrQO|IhcA>? M3zNVpJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MYiyNlE5ODNyOB?=
Sk-Hep1 M1uyW2NmdGxiVnnhZoltcXS7IFHzd4F6 NXLlXJQyOC1zNTFOwG0> MljuO|IhcA>? MXjy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? M3viXlIzOThyM{C4
Huh-7 MlnxR4VtdCCYaXHibYxqfHliQYPzZZk> M2rvfFAuOTVizszN NXH6U3J{PzJiaB?= NFrr[XZz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MonWNlIyQDB|MEi=
PLC5 M3fWNWFxd3C2b4Ppd{BCe3OjeR?= MnvtNE0yPSEQvF2= MnyyNlQhcA>? M1HZfIlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MYiyNlE5ODNyOB?=
Hep3B MYrBdI9xfG:|aYOgRZN{[Xl? M1zCTFAuOTVizszN M1q0Z|I1KGh? Mn3ybY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MXWyNlE5ODNyOB?=
Sk-Hep1 NFy2b2VCeG:ydH;zbZMhSXO|YYm= NV3LfmxKOC1zNTFOwG0> M2i5SFI1KGh? NEizS3ZqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MYmyNlE5ODNyOB?=
Huh-7 NHK3c4lCeG:ydH;zbZMhSXO|YYm= NUHzcHYyOC1zNTFOwG0> MWqyOEBp M{npUolv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MVuyNlE5ODNyOB?=
PLC5 MkLYSpVv[3Srb36gRZN{[Xl? MVewMVExKM7:TR?= M4fIS|I1KGh? M37sToNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? MVuyNlE5ODNyOB?=
Hep3B NG\5PFZHfW6ldHnvckBCe3OjeR?= NIXEcYExNTFyIN88US=> MnPmNlQhcA>? NFixNGZk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? MojINlIyQDB|MEi=
Sk-Hep1 MVPGeY5kfGmxbjDBd5NigQ>? NGnOOZgxNTFyIN88US=> NV3sWJM6OjRiaB?= NVK4eVhC[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NGntZnUzOjF6MEOwPC=>
Huh-7 NVLVfZV1TnWwY4Tpc44hSXO|YYm= NEDXUHMxNTFyIN88US=> NIPuRo4zPCCq NV7oPGVY[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w MkD1NlIyQDB|MEi=
SW780 MnLWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTmfGdEPSCm MV;JR|UxRTVyIH7N Mn;rNlEyOTl4NkG=
RT112 Mkf4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF[3V4I2KGR? Mn3JTWM2OD1zNTDuUS=> NHXaRpMzOTFzOU[2NS=>
RT4 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{n6dlUh\A>? MX;JR|UxRTVibl2= M1nu[|IyOTF7Nk[x
JMSU1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlG0OUBl MmHuTWM2OD13MDDuUS=> M4DGT|IyOTF7Nk[x
J82 NEjRb|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVy1JIQ> NHLPdmdKSzVyPUG0NFAhdk1? M3j0dFIyOTF7Nk[x
97-7 M{i5UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4S2fVUh\A>? MVnJR|UxRTFyMECgcm0> M3HCdFIyOTF7Nk[x
RT112 MWHGeY5kfGmxbjDBd5NigQ>? MYS1NFAhdk1? NV25cW5qOjRiaB?= MnXabY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| M33QU|IyOTF7Nk[x
RT4 M4XsZ2Z2dmO2aX;uJGF{e2G7 NXzGW|dFPTByIH7N M2PGW|I1KGh? M2PP[Ilv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MVeyNVEyQTZ4MR?=
MGH-U3 MXrGeY5kfGmxbjDBd5NigQ>? MX[1NFAhdk1? MlTZNlQhcA>? M3LUSIlv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= NUi4eYE5OjFzMUm2OlE>
SW780 M1zNRWZ2dmO2aX;uJGF{e2G7 MX:1NFAhdk1? MViyOEBp M2D6PYlv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= M4flRlIyOTF7Nk[x
97-7 NXnvUY17TnWwY4Tpc44hSXO|YYm= NHSwXJo2ODBibl2= Mnz5NlQhcA>? M4G1Nolv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MX2yNVEyQTZ4MR?=
 J807C NV3tWm9qS2WubDDWbYFjcWyrdImgRZN{[Xl? MkXGNE01ODBibl2= MWC0PEBp NXTlbJFtcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MX6xOVU6QDhzNB?=
Y373C MVLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1rC[FAuPDByIH7N NIfTN2Y1QCCq MV\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M17jNVE2PTl6OEG0
K650E MW\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MmjZNE01ODBibl2= MkS4OFghcA>? M1XFOIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NGLuOHcyPTV7OEixOC=>
G384D MWjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MoLHNE01ODBibl2= NIrnT3E1QCCq NX\neHdKcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M2XEe|E2PTl6OEG0
F384L MV3D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NXXLcY96OC12MECgcm0> NE[wWlg1QCCq MVfpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MoWyNVU2QTh6MUS=
KMS11 NH\ERphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mmn1O|IhcA>? NXXhU4YzUUN3ME25NEBvVQ>? Mn7FNVU2QTh6MUS=
KMS18 NEfDbmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1Hvd|czKGh? NI\1N5BKSzVyPUW1NEBvVQ>? NYnYOoE3OTV3OUi4NVQ>
OPM2 MoS1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUO0XFNJPzJiaB?= NGXuTHdKSzVyPUmwJI5O MWCxOVU6QDhzNB?=
H929 NHvSd|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1HRclczKGh? Mk\GTWM2OD5iMkWwNEBvVQ>? NV;kVIZ{OTV3OUi4NVQ>
8226 NWD5VYUzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfTO|IhcA>? NVvFeFBpUUN3ME6gNlUxOCCwTR?= MUSxOVU6QDhzNB?=
U266 MojFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjIO5g4OiCq NISwdWpKSzVyPjCyOVAxKG6P MVSxOVU6QDhzNB?=

... Click to View More Cell Line Experimental Data

In vivo Dovitinib induces both cytostatic and cytotoxic responses in vivo resulting in regression of FGFR3-expressing tumors.[1] Dovitinib shows a dose- and exposure-dependent inhibition of target receptor tyrosine kinases (RTKs) expressed in tumor xenografts. Dovitinib potently inhibits tumor growth of six HCC lines. Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFRβ/VEGFR2 signaling pathways. In an orthotopic model, Dovitinib potently inhibits primary tumor growth and lung metastasis and significantly prolonged mouse survival. [2] Administration of Dovitinib results in significant tumor growth inhibition and tumor regressions, including large, established tumors (500-1,000 mm3). [3]

Protocol

Kinase Assay:[1]
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In vitro kinase assays:

The inhibitory concentration of 50% (IC50) values for the inhibition of RTKs by Dovitinib are determined in a time-resolved fluorescence (TRF) or radioactive format, measuring the inhibition by Dovitinib of phosphate transfer to a substrate by the respective enzyme. The kinase domains of FGFR3, FGFR1, PDGFRβ, and VEGFR1-3 are assayed in 50 mM HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid), pH 7.0, 2 mM MgCl2, 10 mM MnCl2 1 mM NaF, 1 mM dithiothreitol (DTT), 1 mg/mL bovine serum albumin (BSA), 0.25 μM biotinylated peptide substrate (GGGGQDGKDYIVLPI), and 1 to 30 μM adenosine triphosphate (ATP) depending on the Km for the respective enzyme. ATP concentrations are at or just below Km. For c-KIT and FLT3 reactions the pH is raised to 7.5 with 0.2 to 8 μM ATP in the presence of 0.25 to 1 μM biotinylated peptide substrate (GGLFDDPSYVNVQNL). Reactions are incubated at room temperature for 1 to 4 hours and the phosphorylated peptide captured on streptavidin-coated microtiter plates containing stop reaction buffer (25 mM EDTA [ethylenediaminetetraacetic acid], 50 mM HEPES, pH 7.5). Phosphorylated peptide is measured with the DELFIA TRF system using a Europium-labeled antiphosphotyrosine antibody PT66. The concentration of Dovitinib for IC50 is calculated using nonlinear regression with XL-Fit data analysis software version 4.1 (IDBS). Inhibition of colony-stimulating factor-1 receptor (CSF-1R), PDGFRα, insulin receptor (InsR), and insulin-like growth factor receptor 1 (IGFR1) kinase activity is determined at ATP concentrations close the Km for ATP.
Cell Research:[1]
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  • Cell lines: B9 cells, MM cell lines
  • Concentrations: 100 nM
  • Incubation Time: 48-96 hours
  • Method: Cell viability is assessed by 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) dye absorbance. Cells are seeded in 96-well plates at a density of 5 × 103 (B9 cells) or 2 × 104 (MM cell lines) cells per well. Cells are incubated with 30 ng/mL aFGF and 100 μg/mL heparin or 1% IL-6 where indicated and increasing concentrations of Dovitinib. For each concentration of Dovitinib, 10 μL aliquots of drug or DMSO diluted in culture medium is added. For drug combination studies, cells are incubated with 0.5 μM dexamethasone, 100 nM Dovitinib, or both simultaneously where indicated. To evaluate the effect of Dovitinib on growth of MM cells adherent to BMSCs, 104 KMS11 cells are cultured on BMSC-coated 96-well plates in the presence or absence of Dovitinib. Plates are incubated for 48 to 96 hours. For assessment of macrophage colony-stimulating factor (M-CSF)-mediated growth, 5 × 103 M-NFS-60 cells/well are incubated with serial dilutions of Dovitinib with 10 ng/mL M-CSF and without granulocyte-macrophage colony-stimulating factor (GM-CSF). After 72 hours cell viability is determined using Cell Titer-Glo Assay. Each experimental condition is performed in triplicate.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: 8-week-old female BNX mice bearing KMS11 cells
  • Formulation: 5 mM citrate buffer
  • Dosages: 10, 30, or 60 mg/kg
  • Administration: Gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 30 mg/mL (76.44 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order:
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 392.43
Formula

C21H21FN6O

CAS No. 405169-16-6
Storage powder
Synonyms N/A

Bio Calculators

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01497392 Completed Adenocarcinoma of the Pancreas|Stage III Pancreatic Cancer|Stage IV Pancreatic Cancer|Unspecified Adult Solid Tumor, Protocol Specific Roswell Park Cancer Institute|National Cancer Institute (NCI)|Novartis March 29, 2012 Phase 1
NCT02048943 Withdrawn Duct Cell Adenocarcinoma of the Pancreas|Recurrent Pancreatic Cancer|Stage III Pancreatic Cancer|Stage IV Pancreatic Cancer|Unspecified Adult Solid Tumor, Protocol Specific Roswell Park Cancer Institute|National Cancer Institute (NCI)|Novartis March 2015 Phase 1
NCT02268435 Withdrawn Gastrointestinal Stromal Tumors Asan Medical Center March 2015 Phase 1
NCT02108782 Withdrawn Gastrinoma|Glucagonoma|Insulinoma|Pancreatic Polypeptide Tumor|Recurrent Islet Cell Carcinoma|Somatostatinoma Academic and Community Cancer Research United|National Cancer Institute (NCI) October 2014 Phase 2
NCT02116803 Completed Solid Tumors Novartis Pharmaceuticals|Novartis May 2014 Phase 2|Phase 3
NCT01994590 Active, not recruiting Prostate Cancer M.D. Anderson Cancer Center|Novartis May 2014 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID