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 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLFTWM2OD1yLkS0PUDPxE1? NVfBXGxvOjV{MEKwO|M>
SupB15-R MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYSxR|hQUUN3ME2wMlU2QCEQvF2= M3;lblI2OjB{MEez
BaF3-pSRα NHTxZlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVHJR|UxRTBwNk[4JO69VQ>? MYeyOVIxOjB5Mx?=
BaF3-p210Bcr-Abl MkTIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmSxTWM2OD1yLk[5NkDPxE1? NYfQWZFCOjV{MEKwO|M>
BaF3-p210Bcr-Abl-T315I NFXXbHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUX1XZRnUUN3ME2yMlYzPiEQvF2= MnfXNlUzODJyN{O=
CCRF-CEM MlfmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLH[GhKSzVyPUCuN|k5KM7:TR?= MUeyOVIxOjB5Mh?=
CEM/C2 NUi0[2ZGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTtd4pKSzVyPUGuNVI2KM7:TR?= MnryNlUzODJyN{K=
Nalm-6 NXGwXlVRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTBwM{iyJO69VQ>? M1HzTFI2OjB{MEey
SEM-K2 MkPBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml;VTWM2OD1yLkCyNkDPxE1? NHPvdJIzPTJyMkC3Ni=>
HB-1119 M1fSeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVftXmFFUUN3ME2wMlAzQCEQvF2= NIjFdIszPTJyMkC3Ni=>
RS4:11 MkmxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{LmWmlEPTB;Mj64NUDPxE1? MWSyOVIxOjB5Mh?=
Nalm-6 NUTEZ|dCSXCxcITvd4l{KEG|c3H5 MX:yJO69VQ>? NEDYeIUzPC92ODDo NFTjXY9qdmS3Y3XzJIFxd3C2b4Ppd{Bz\XO3bITpcochcW5iYXLveZQhPzJnIH;mJINmdGxiZHXheIgh[W[2ZYKgNlQhcCC2cnXheI1mdnRiYX7kJFgyLSCjZoTldkA1QCCq NGS4cokzPTJyMkC3Ni=>
SEM-K2 NWHYPYhkSXCxcITvd4l{KEG|c3H5 M3TJdFAvOS9zIN88US=> NFvoXYMzPCCq Ml3qbY5lfWOnczDlZZJtgSCjcH;weI9{cXNib3[gV2VONUt{IHPlcIx{KGG2IECuNUDPxE1iYX\0[ZIhOjRiaB?= NF72eZkzPTJyMkC3Ni=>
HCT-116 NEnDTVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEf1dIpKSzVyPUOuNFUxNjV6IN88US=> NVTDdIJbOjR2OUW3OVA>
HT-29 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3:zR2lEPTB;NT6yNU46OyEQvF2= NUDtXnp1OjR2OUW3OVA>
SW-480 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGLxUG9KSzVyPUSuN|MxNjR5IN88US=> M1zRZVI1PDl3N{Ww
CaCO2 NEXCOnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTNwMkOwMlY1KM7:TR?= MUKyOFQ6PTd3MB?=
LS174T NWfL[HRjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Moi4TWM2OD12LkOzNE41PyEQvF2= NYjhXppVOjR2OUW3OVA>
HEC-1A NEDEfFJHfW6ldHnvckBCe3OjeR?= MV[wMlA2NzBwMT:wMlUh|ryP MkC0O|IhcA>? MojPZ4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> MV[yOFQ6PTd3MB?=
AN3CA MVnGeY5kfGmxbjDBd5NigQ>? M4TaSVAvODVxMD6xM|AvPSEQvF2= Mni3O|IhcA>? MYTjZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> MV6yOFQ6PTd3MB?=
MFE-296  NX;NVWFtTnWwY4Tpc44hSXO|YYm= NF31WmgxNjB3L{CuNU8xNjVizszN M{XQOVczKGh? NWm0O|h2[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? MkXHNlQ1QTV5NUC=
UMC3 NYq2XGZHS2WubDDWbYFjcWyrdImgRZN{[Xl? NWS3[4JTOS1zMDFOwG0> NF;WeoI4OiCq MX;pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NHKzcm4zPDN{NUS2NS=>
5637 NGTHUohE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NFLRZYcyNTFyIN88US=> NIPSZpA4OiCq MnGxbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NXPqSZVmOjR|MkW0OlE>
HU456 M3T6UmNmdGxiVnnhZoltcXS7IFHzd4F6 M4C4d|EuOTBizszN Mlu4O|IhcA>? MkPJbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M1P2ZlI1OzJ3NE[x
MGHU4 M1rJWGNmdGxiVnnhZoltcXS7IFHzd4F6 MYixMVExKM7:TR?= MoL4O|IhcA>? Mo[4bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> Ml30NlQ{OjV2NkG=
HT1376 NV3KPXg6S2WubDDWbYFjcWyrdImgRZN{[Xl? MmfZNU0yOCEQvF2= Mn;zO|IhcA>? MVrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M2PEflI1OzJ3NE[x
RT112 MVfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NIjzOFkyNTFyIN88US=> M1flTFczKGh? NFHvS|hqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MXiyOFMzPTR4MR?=
T24 MnTER4VtdCCYaXHibYxqfHliQYPzZZk> NHqzflcyNTFyIN88US=> MUi3NkBp NVXMNIFCcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MkGyNlQ{OjV2NkG=
BFTC905 M1fjUGNmdGxiVnnhZoltcXS7IFHzd4F6 M1vQXlEuOTBizszN M2D6SFczKGh? NIHwOWlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NX;ndJRpOjR|MkW0OlE>
TCC-SUP NHmwRlRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NWr4U5BROS1zMDFOwG0> Mm\nO|IhcA>? NF;TT3RqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MlS0NlQ{OjV2NkG=
RT4 M4PmZ2NmdGxiVnnhZoltcXS7IFHzd4F6 MljxNU0yOCEQvF2= MWG3NkBp NXHSO|ZscW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M{n0V|I1OzJ3NE[x
HONE1 NF3pVYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17IZVAvOS1zMDFOwG0> Mn\TOFjDqGh? NYPhW4ZNcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M1\KOVI1OjN6MEm0
HNE1 Mk[wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NY\BN4ZOOC5zLUGwJO69VQ>? NXHNZo1qPDkEoHi= NXOxTFYycW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NGHleWMzPDJ|OEC5OC=>
CNE2  NI\zNYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYjNc4hyOC5zLUGwJO69VQ>? NWnFV|NQPDkEoHi= NY\LZlFPcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MlrxNlQzOzhyOUS=
C666-1 NFrqb3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHjpXncxNjFvMUCg{txO M1LTTFQ5yqCq M2K1VIlv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NFXBXHczPDJ|OEC5OC=>
HeLa NV;0VJh[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NULXPYgzOC5zLUGwJO69VQ>? M{jxR|I1KGh? NYrUe5pOcW6mdXPld{BIOi:PIHHydoV{fCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MYiyOFI{QDB7NB?=
Hep3B NIOxWHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzHNE4yNTFyIN88US=> NH;2U2czPCCq NXjQXFVZcW6mdXPld{BIOsLiYYLy[ZN1yqB? NWXZWYVjOjR{M{iwPVQ>
HepG2 MmjtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWS0PEBp NVXObW5sUUN3ME2yMlczPyEEsTCwMlQzQSEQvF2= M{WxTlI{PTR4NUmx
Hep3B MoT6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY[0PEBp NILBPGZKSzVyPUSuNlI{KMLzIECuPFM6KM7:TR?= M{fPNFI{PTR4NUmx
PLC/PRF5 Mkn5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE\WO4M1QCCq M1[xbmlEPTB;MU[uNVIxKMLzIESuNFAyKM7:TR?= Ml3aNlM2PDZ3OUG=
Huh7 Mn7aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUO0PEBp NV\oe|JjUUN3ME2xOU4xODdiwsGgO{4{OzRizszN M4jLW|I{PTR4NUmx
HepG2 M1TyU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfIW5V6PzJiaB?= MXvJR|UxRTFwMkCwJOKyKDBwMkK2JO69VQ>? Mn\ONlM2PDZ3OUG=
Hep3B MojLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHv5SYw4OiCq M2Xn[mlEPTB;MD64PVIhyrFiMD6wOFQh|ryP NYnaZWtPOjN3NE[1PVE>
PLC/PRF5 NGPSNlFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoP5O|IhcA>? NHjFb21KSzVyPUOuNVExKMLzIECuN|M4KM7:TR?= NHG5coozOzV2NkW5NS=>
Huh7 MlmwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XqcVczKGh? MWDJR|UxRTNwOUiwJOKyKDBwOECzJO69VQ>? NHu1V|gzOzV2NkW5NS=>
MFE280 NV;MZYduT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHHVS5BKSzVyPUCuOFIhyrFiMD6wOkDPxE1? NIW5emszOzR2M{iwOS=>
AN3CA Mnr0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\oTWM2OD1yLkWwJOKyKDBwMUCg{txO M4fzRlI{PDR|OEC1
HEC155 NETmUHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXnJR|UxRTBwNk[gxtEhOC5yOTFOwG0> MX6yN|Q1OzhyNR?=
MFE296 NWfm[5pkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVnNNGg1UUN3ME2wMlY3KMLzIECuNVkh|ryP NX72XXY{OjN2NEO4NFU>
SPAC1S NFK4S3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlHYTWM2OD1yLke3JOKyKDBwMEig{txO NHrDZZMzOzR2M{iwOS=>
RL952 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPYNplvUUN3ME2wMlk{KMLzIECuNFEh|ryP NV\LSGp[OjN2NEO4NFU>
EN1 NEnMcnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTwRVZLUUN3ME2xMlAzKMLzIECuNlUh|ryP M2rXfFI{PDR|OEC1
SNGII M1jtdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVHBbllCUUN3ME2xMlI1KMLzIECuNlgh|ryP MVOyN|Q1OzhyNR?=
ISHIKAWA M1P6VWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4iwb2lEPTB;MT6zNEDDuSByLkGxJO69VQ>? MmTzNlM1PDN6MEW=
HEC1A MoTFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlThTWM2OD1zLkO0JOKyKDBwM{Cg{txO M1HBR|I{PDR|OEC1
KLE NWTxdFlIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWfJR|UxRTFwM{egxtEhOC5yMjFOwG0> NYq0cG54OjN2NEO4NFU>
SNGM M1\n[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{H1S2lEPTB;MT60NkDDuSByLkGzJO69VQ>? Mle0NlM1PDN6MEW=
USPC2 MkLKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4S2NWlEPTB;MT62NkDDuSByLkCxJO69VQ>? NI\udYozOzR2M{iwOS=>
EN M4[1bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nZVmlEPTB;MT62OkDDuSByLkCxJO69VQ>? NITyO5EzOzR2M{iwOS=>
MFE319 NFzvT3lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFrlWFhKSzVyPUGuPFchyrFiMD60OUDPxE1? NVzjZ|lCOjN2NEO4NFU>
EFE184 MmPrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1P4UGlEPTB;Mj6wOEDDuSByLkGzJO69VQ>? NYO5TnJHOjN2NEO4NFU>
ECC1 NYjHU3NPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXXJR|UxRTJwMEegxtEhOC5yMTFOwG0> NUnWS|FyOjN2NEO4NFU>
HEC1B MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTZTWM2OD1{LkW3JOKyKDBwMkOg{txO M{Hje|I{PDR|OEC1
USPC1 Ml;lS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH;sTllKSzVyPUKuOlAhyrFiMD6xN{DPxE1? MlPhNlM1PDN6MEW=
SPAC1L NX\meFFGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoD2TWM2OD1|LkC2JOKyKDFwMUSg{txO M2fIeFI{PDR|OEC1
HUVEC MUnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MWGwMVI2KM7:TR?= MX63NkBp MmDZSG1UVw>? Mmq5bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NVLEUI96OjN{MkiwNVc>
HMVEC M3\LZmNmdGxiVnnhZoltcXS7IFHzd4F6 NH3ifVQxNTJ3IN88US=> MYm3NkBp M2\h[mROW09? NHHLUJdqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MonYNlMzOjhyMUe=
MHCC-97H NIDST4RE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MnTDNE0zPSEQvF2= NF7iNY04OiCq NFLwWJNFVVOR MVTpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MXOyN|IzQDBzNx?=
SMMC7721 NHLjNo1E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVTUWI1wOC1{NTFOwG0> MXy3NkBp MmHnSG1UVw>? NEXzNm5qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NHrlR5czOzJ{OECxOy=>
Huh-7 M3PNZ2Fxd3C2b4Ppd{BCe3OjeR?= NY\6dlVWOC1zMj61JO69VQ>? MYOyOEBp MlLDSG1UV8Li NVTlSWx[e2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NX7lXGp3OjJ{M{C0O|k>
Sk-Hep1 M2i2fWFxd3C2b4Ppd{BCe3OjeR?= Mn:yNE0yOi53IN88US=> M4jo[|I1KGh? M1zGb2ROW00EoB?= M3zHWZNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NVvvTIxZOjJ{M{C0O|k>
Hep3B M1XEVmFxd3C2b4Ppd{BCe3OjeR?= NF3BVFkxNTF{LkWg{txO MX[yOEBp MYDEUXNQyqB? NYjBe3N{e2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NFfXcJczOjJ|MES3PS=>
PLC5 MkTmRZBweHSxc3nzJGF{e2G7 MX[wMVEzNjVizszN NX7mUGhnOjRiaB?= M3HkVWROW00EoB?= MXjz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M1vBTFIzOjNyNEe5
PLC5 MkDPR4VtdCCYaXHibYxqfHliQYPzZZk> MkjLNE0yPSEQvF2= NHWzeFc4OiCq NETjcWtz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NVHMTJE1OjJzOECzNFg>
Hep3B NXjvNWEyS2WubDDWbYFjcWyrdImgRZN{[Xl? NELrbHIxNTF3IN88US=> NH;4XGo4OiCq NEK1SYNz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NXnWR5BWOjJzOECzNFg>
Sk-Hep1 M3f6fGNmdGxiVnnhZoltcXS7IFHzd4F6 NGDBcJMxNTF3IN88US=> M3T6UlczKGh? MXny[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NUfTfZRxOjJzOECzNFg>
Huh-7 M4Tv[mNmdGxiVnnhZoltcXS7IFHzd4F6 M{LEdVAuOTVizszN MXG3NkBp MkDWdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MkTPNlIyQDB|MEi=
PLC5 MYTBdI9xfG:|aYOgRZN{[Xl? MWSwMVE2KM7:TR?= M1;EN|I1KGh? NWjSTpJCcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NH\RSI0zOjF6MEOwPC=>
Hep3B NGHjXFZCeG:ydH;zbZMhSXO|YYm= M1TxZlAuOTVizszN NXTEVWRxOjRiaB?= M172Z4lv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MX:yNlE5ODNyOB?=
Sk-Hep1 M{i1NGFxd3C2b4Ppd{BCe3OjeR?= MYqwMVE2KM7:TR?= NUTvOXNCOjRiaB?= MYjpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? MW[yNlE5ODNyOB?=
Huh-7 NHPFW3FCeG:ydH;zbZMhSXO|YYm= NFHDTpIxNTF3IN88US=> NF3vNFczPCCq NYOwdXZGcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NV;WNYFCOjJzOECzNFg>
PLC5 MV\GeY5kfGmxbjDBd5NigQ>? M1XZSVAuOTBizszN MXqyOEBp M325eINifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? M1nN[|IzOThyM{C4
Hep3B NUm4PZpiTnWwY4Tpc44hSXO|YYm= NWP2fZZCOC1zMDFOwG0> NGTDOnczPCCq M{fyfINifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? NUWxO29wOjJzOECzNFg>
Sk-Hep1 MVvGeY5kfGmxbjDBd5NigQ>? Ml;XNE0yOCEQvF2= Mn;RNlQhcA>? MnHQZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v MWOyNlE5ODNyOB?=
Huh-7 Mme2SpVv[3Srb36gRZN{[Xl? MYmwMVExKM7:TR?= Mnf3NlQhcA>? Mkj2Z4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v M{\Wb|IzOThyM{C4
SW780 NUDFWHRlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXO1JIQ> NFr4blBKSzVyPUWwJI5O MUiyNVEyQTZ4MR?=
RT112 NFTmO3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEnUOY02KGR? NFLtZZNKSzVyPUG1JI5O NInHOG8zOTFzOU[2NS=>
RT4 M3XCOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVG1JIQ> M1;Fe2lEPTB;NTDuUS=> MXuyNVEyQTZ4MR?=
JMSU1 MkL0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY[1JIQ> NW\vfHZXUUN3ME21NEBvVQ>? MXGyNVEyQTZ4MR?=
J82 NYT6[VA1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWm1JIQ> MmDNTWM2OD1zNECwJI5O MXiyNVEyQTZ4MR?=
97-7 NHLSb4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIj3bnI2KGR? NVLJeZVKUUN3ME2xNFAxKG6P MkfYNlEyOTl4NkG=
RT112 NHjFc3ZHfW6ldHnvckBCe3OjeR?= MWe1NFAhdk1? NU\KeHdjOjRiaB?= NE[0ZYpqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MWmyNVEyQTZ4MR?=
RT4 NV;uRYVFTnWwY4Tpc44hSXO|YYm= M2jD[|UxOCCwTR?= NIj1NYozPCCq MWDpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NHTwOY8zOTFzOU[2NS=>
MGH-U3 MYXGeY5kfGmxbjDBd5NigQ>? M2[wcFUxOCCwTR?= NEnJN|YzPCCq MnzxbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NYX6T3U{OjFzMUm2OlE>
SW780 MnnoSpVv[3Srb36gRZN{[Xl? MYC1NFAhdk1? NEPiVnEzPCCq M3q3[4lv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MUWyNVEyQTZ4MR?=
97-7 M{m4dGZ2dmO2aX;uJGF{e2G7 MlLwOVAxKG6P MUSyOEBp M16yPYlv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= NHOweJQzOTFzOU[2NS=>
 J807C NUDKNGhPS2WubDDWbYFjcWyrdImgRZN{[Xl? MljiNE01ODBibl2= MoPMOFghcA>? NGjyb|RqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NVnQUXViOTV3OUi4NVQ>
Y373C MW\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> M{nmflAuPDByIH7N NXPr[nFFPDhiaB?= NHXXZohqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Mli1NVU2QTh6MUS=
K650E MmnyR4VtdCCYaXHibYxqfHliQYPzZZk> Mk\aNE01ODBibl2= NGPKbGo1QCCq NFXFN2xqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MW[xOVU6QDhzNB?=
G384D M1nJXWNmdGxiVnnhZoltcXS7IFHzd4F6 NFy4Z5AxNTRyMDDuUS=> MXS0PEBp NFHqSlhqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NY\DfYdJOTV3OUi4NVQ>
F384L MW\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MUWwMVQxOCCwTR?= MW[0PEBp MVPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NVO5b3hrOTV3OUi4NVQ>
KMS11 Mn7ES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYS3NkBp NVHoUHBrUUN3ME25NEBvVQ>? NX;KVmo4OTV3OUi4NVQ>
KMS18 NUfEfFVLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknVO|IhcA>? MkC1TWM2OD13NUCgcm0> MV2xOVU6QDhzNB?=
OPM2 NVT0OFR5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWOxV3VWPzJiaB?= MWrJR|UxRTlyIH7N MoSwNVU2QTh6MUS=
H929 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYO3NkBp NVuyRVZkUUN3ME6gNlUxOCCwTR?= NYWyZpZWOTV3OUi4NVQ>
8226 M3TxOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3\URVczKGh? NEHncppKSzVyPjCyOVAxKG6P NXS0ZmZxOTV3OUi4NVQ>
U266 MnjuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PmTFczKGh? M2\3[WlEPTB-IEK1NFAhdk1? NHf2c|EyPTV7OEixOC=>

... 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 individually and in order:
30% PEG400+0.5% Tween80+5% propylene glycol
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