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 MnXyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTBwNES5JO69VQ>? M3rZWFI2OjB{MEez
SupB15-R M2rtVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{PxTGlEPTB;MD61OVgh|ryP MUKyOVIxOjB5Mx?=
BaF3-pSRα NIj0NoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTBwNk[4JO69VQ>? MnjwNlUzODJyN{O=
BaF3-p210Bcr-Abl M1HZXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLHTWM2OD1yLk[5NkDPxE1? NYjlWIFiOjV{MEKwO|M>
BaF3-p210Bcr-Abl-T315I MlPxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnmOGFUUUN3ME2yMlYzPiEQvF2= M3rq[VI2OjB{MEez
CCRF-CEM NEPie4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGnNdnhKSzVyPUCuN|k5KM7:TR?= MVWyOVIxOjB5Mh?=
CEM/C2 NVX3fWUzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnWwTWM2OD1zLkGyOUDPxE1? NIfHN4YzPTJyMkC3Ni=>
Nalm-6 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoXsTWM2OD1yLkO4NkDPxE1? M3y1U|I2OjB{MEey
SEM-K2 M{DmXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3rDb2lEPTB;MD6wNlIh|ryP Mln3NlUzODJyN{K=
HB-1119 M3vkcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWriSWJSUUN3ME2wMlAzQCEQvF2= MmC1NlUzODJyN{K=
RS4:11 M2j0VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXPJR|UxRTJwOEGg{txO NVy1[oVGOjV{MEKwO|I>
Nalm-6 MUfBdI9xfG:|aYOgRZN{[Xl? M4j2VVIh|ryP M2PidFI1NzR6IHi= NX7WZldzcW6mdXPld{BieG:ydH;zbZMhemW|dXz0bY5oKGmwIHHic5V1KDd{JTDv[kBk\WyuIHTlZZRpKGGodHXyJFI1KGhidILlZZRu\W62IHHu[EA5OSViYX\0[ZIhPDhiaB?= NEjIdVYzPTJyMkC3Ni=>
SEM-K2 MkTCRZBweHSxc3nzJGF{e2G7 NX\BeXFwOC5zL{Gg{txO MmnoNlQhcA>? MWPpcoR2[2W|IHXhdox6KGGyb4D0c5NqeyCxZjDTSW0uUzJiY3XscJMh[XRiMD6xJO69VSCjZoTldkAzPCCq M1OxdlI2OjB{MEey
HCT-116 M4PHT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2L5bGlEPTB;Mz6wOVAvPThizszN MUGyOFQ6PTd3MB?=
HT-29 NEPkT2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGT0UnVKSzVyPUWuNlEvQTNizszN M3LhRVI1PDl3N{Ww
SW-480 MnPyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfSPHhKSzVyPUSuN|MxNjR5IN88US=> MWGyOFQ6PTd3MB?=
CaCO2 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWTJR|UxRTNwMkOwMlY1KM7:TR?= Mln5NlQ1QTV5NUC=
LS174T Mn70S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4XHR2lEPTB;ND6zN|AvPDdizszN NEH5bWczPDR7NUe1NC=>
HEC-1A MUXGeY5kfGmxbjDBd5NigQ>? NYLwcVh4OC5yNT:wMlEwOC53IN88US=> MoLTO|IhcA>? M2ntTINifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v MVyyOFQ6PTd3MB?=
AN3CA NUfaW4RxTnWwY4Tpc44hSXO|YYm= M37V[FAvODVxMD6xM|AvPSEQvF2= MYm3NkBp NV3Vc4NI[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? Ml74NlQ1QTV5NUC=
MFE-296  M1nMOGZ2dmO2aX;uJGF{e2G7 NYTp[ZdTOC5yNT:wMlEwOC53IN88US=> NYDZcpZpPzJiaB?= MWjjZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> NF;nWYczPDR7NUe1NC=>
UMC3 MkLkR4VtdCCYaXHibYxqfHliQYPzZZk> Mnv1NU0yOCEQvF2= M{[4fFczKGh? MV3pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MkfZNlQ{OjV2NkG=
5637 MnS4R4VtdCCYaXHibYxqfHliQYPzZZk> M1m4RlEuOTBizszN MY[3NkBp NYG4fpZJcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MUCyOFMzPTR4MR?=
HU456 NWXUb5ZvS2WubDDWbYFjcWyrdImgRZN{[Xl? NYn1NmJPOS1zMDFOwG0> NWTnbY5wPzJiaB?= M2f3N4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NYXVXFFMOjR|MkW0OlE>
MGHU4 NUjQZYFGS2WubDDWbYFjcWyrdImgRZN{[Xl? NITTZ2YyNTFyIN88US=> NY\NcHhIPzJiaB?= NXX3fm1ocW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M32zT|I1OzJ3NE[x
HT1376 MnrTR4VtdCCYaXHibYxqfHliQYPzZZk> MoLPNU0yOCEQvF2= M{\mcFczKGh? MlPUbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NV7pXINHOjR|MkW0OlE>
RT112 M2T0TGNmdGxiVnnhZoltcXS7IFHzd4F6 NYjOTVFZOS1zMDFOwG0> Ml3kO|IhcA>? M1TPNYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MWOyOFMzPTR4MR?=
T24 M37iV2NmdGxiVnnhZoltcXS7IFHzd4F6 NULKeXE3OS1zMDFOwG0> NETqS2w4OiCq MoTpbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M4nEcFI1OzJ3NE[x
BFTC905 M1S1PWNmdGxiVnnhZoltcXS7IFHzd4F6 MXmxMVExKM7:TR?= NXjiTolYPzJiaB?= MUHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NXjQNZEzOjR|MkW0OlE>
TCC-SUP NF[3UIJE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NFnvR4UyNTFyIN88US=> NF3aUlI4OiCq M3HMeolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MmDUNlQ{OjV2NkG=
RT4 MlnXR4VtdCCYaXHibYxqfHliQYPzZZk> MnT6NU0yOCEQvF2= MmrmO|IhcA>? NYDu[2pScW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MUSyOFMzPTR4MR?=
HONE1 NEPqXJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVuwMlEuOTBizszN M4nWWFQ5yqCq NULR[HlWcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NGTy[HEzPDJ|OEC5OC=>
HNE1 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnjaNE4yNTFyIN88US=> M13DSVQ5yqCq NFzqcXhqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MknTNlQzOzhyOUS=
CNE2  NHPrVldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWqwMlEuOTBizszN M{nRblQ5yqCq MWTpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MmDuNlQzOzhyOUS=
C666-1 NULQS5dYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;TcpcxNjFvMUCg{txO NIP0Tlk1QMLiaB?= M{LmOolv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NYLOXVVUOjR{M{iwPVQ>
HeLa NGHS[3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvENE4yNTFyIN88US=> MnPUNlQhcA>? NGTVfWlqdmS3Y3XzJGczN01iYYLy[ZN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MWeyOFI{QDB7NB?=
Hep3B M1XSVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3fMO|AvOS1zMDFOwG0> M2mzblI1KGh? NYrZNJV5cW6mdXPld{BIOsLiYYLy[ZN1yqB? NISxR5kzPDJ|OEC5OC=>
HepG2 M{\ne2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWq0PEBp NHi1UHBKSzVyPUKuO|I4KMLzIECuOFI6KM7:TR?= NFG1WpgzOzV2NkW5NS=>
Hep3B NFrq[XZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYfHcZhDPDhiaB?= NHjpUlFKSzVyPUSuNlI{KMLzIECuPFM6KM7:TR?= MXKyN|U1PjV7MR?=
PLC/PRF5 NGDPOnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmrJOFghcA>? MknlTWM2OD1zNj6xNlAhyrFiND6wNFEh|ryP NVXPVphUOjN3NE[1PVE>
Huh7 MmDwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFfJNFM1QCCq NVfLXIxCUUN3ME2xOU4xODdiwsGgO{4{OzRizszN NXO5fYdpOjN3NE[1PVE>
HepG2 MmKxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXm3NkBp NG\ucnNKSzVyPUGuNlAxKMLzIECuNlI3KM7:TR?= NWfB[XdyOjN3NE[1PVE>
Hep3B MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYDoSHJ[PzJiaB?= NF74U4VKSzVyPUCuPFkzKMLzIECuNFQ1KM7:TR?= NIrTPIIzOzV2NkW5NS=>
PLC/PRF5 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWS3NkBp NFjPSHFKSzVyPUOuNVExKMLzIECuN|M4KM7:TR?= NGTI[IIzOzV2NkW5NS=>
Huh7 M4W3OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV63NkBp MYXJR|UxRTNwOUiwJOKyKDBwOECzJO69VQ>? NIj4V5QzOzV2NkW5NS=>
MFE280 M2S0N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGfKdVdKSzVyPUCuOFIhyrFiMD6wOkDPxE1? MYCyN|Q1OzhyNR?=
AN3CA MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWXJR|UxRTBwNUCgxtEhOC5zMDFOwG0> MoXqNlM1PDN6MEW=
HEC155 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIq2WXpKSzVyPUCuOlYhyrFiMD6wPUDPxE1? NH7rOVUzOzR2M{iwOS=>
MFE296 M3TBUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTBwNk[gxtEhOC5zOTFOwG0> NUfVO4hoOjN2NEO4NFU>
SPAC1S M1f4cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPuZYpwUUN3ME2wMlc4KMLzIECuNFgh|ryP M13sRlI{PDR|OEC1
RL952 NYW4NVhmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYjsRoxwUUN3ME2wMlk{KMLzIECuNFEh|ryP NWPKcYlNOjN2NEO4NFU>
EN1 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWXJR|UxRTFwMEKgxtEhOC5{NTFOwG0> NHzpOWgzOzR2M{iwOS=>
SNGII M1;DXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmP5TWM2OD1zLkK0JOKyKDBwMkig{txO NFfDeXQzOzR2M{iwOS=>
ISHIKAWA NXnpdHJMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4TwNWlEPTB;MT6zNEDDuSByLkGxJO69VQ>? NWTmPW9KOjN2NEO4NFU>
HEC1A MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MW\JR|UxRTFwM{SgxtEhOC5|MDFOwG0> NHHWdngzOzR2M{iwOS=>
KLE NXX2SWpGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MonHTWM2OD1zLkO3JOKyKDBwMEKg{txO NETsdFczOzR2M{iwOS=>
SNGM MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRTFwNEKgxtEhOC5zMzFOwG0> M2PzelI{PDR|OEC1
USPC2 NXLU[Y5ZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV\JR|UxRTFwNkKgxtEhOC5yMTFOwG0> M4LofFI{PDR|OEC1
EN NFLNNHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUXKc4h7UUN3ME2xMlY3KMLzIECuNFEh|ryP MkH6NlM1PDN6MEW=
MFE319 NF;UW4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWfJR|UxRTFwOEegxtEhOC52NTFOwG0> NE\E[XQzOzR2M{iwOS=>
EFE184 MljKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF7WVHFKSzVyPUKuNFQhyrFiMD6xN{DPxE1? M3PQRVI{PDR|OEC1
ECC1 NFK0VFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnzTWM2OD1{LkC3JOKyKDBwMEGg{txO NVqyTnJROjN2NEO4NFU>
HEC1B MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13zN2lEPTB;Mj61O{DDuSByLkKzJO69VQ>? MofYNlM1PDN6MEW=
USPC1 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPpfJRsUUN3ME2yMlYxKMLzIECuNVMh|ryP NXq4SYw{OjN2NEO4NFU>
SPAC1L MnHQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoLTTWM2OD1|LkC2JOKyKDFwMUSg{txO NUXleIZROjN2NEO4NFU>
HUVEC MULD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NVHyT2pbOC1{NTFOwG0> NUi4bo53PzJiaB?= M2DoSGROW09? NF\TTlNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M1jz[VI{OjJ6MEG3
HMVEC MVvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MknCNE0zPSEQvF2= M1\lPVczKGh? NGf6e3FFVVOR Mnr2bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MWqyN|IzQDBzNx?=
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Huh-7 Mkm3RZBweHSxc3nzJGF{e2G7 M4rTZlAuOTJwNTFOwG0> NF3h[mQzPCCq MUXEUXNQyqB? Mn;id4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NHm3b|kzOjJ|MES3PS=>
Sk-Hep1 M1PZT2Fxd3C2b4Ppd{BCe3OjeR?= Mkj2NE0yOi53IN88US=> M{jnZVI1KGh? M4rPU2ROW00EoB?= NVnP[5I3e2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? M4PPbVIzOjNyNEe5
Hep3B MkLxRZBweHSxc3nzJGF{e2G7 M{Lp[lAuOTJwNTFOwG0> MXSyOEBp MWTEUXNQyqB? MXjz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NYrEfY1MOjJ{M{C0O|k>
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PLC5 MWjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1;yNVAuOTVizszN M4r6b|czKGh? M4HZUpJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MX:yNlE5ODNyOB?=
Hep3B NIq5e3ZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? Mn3VNE0yPSEQvF2= NGXkTG44OiCq M1zhSpJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NF3jT3AzOjF6MEOwPC=>
Sk-Hep1 MofjR4VtdCCYaXHibYxqfHliQYPzZZk> M3zT[lAuOTVizszN NWD1cXI{PzJiaB?= MWny[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? Ml3wNlIyQDB|MEi=
Huh-7 NUTP[pd3S2WubDDWbYFjcWyrdImgRZN{[Xl? MVOwMVE2KM7:TR?= MYe3NkBp NWfHc2JXemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg NF:xdIwzOjF6MEOwPC=>
PLC5 MnrwRZBweHSxc3nzJGF{e2G7 M1i2T|AuOTVizszN Mm\kNlQhcA>? MVLpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? M1;melIzOThyM{C4
Hep3B NY\EU2tpSXCxcITvd4l{KEG|c3H5 MlnSNE0yPSEQvF2= NIXFO4szPCCq MUTpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? NEfaOpIzOjF6MEOwPC=>
Sk-Hep1 NWTMR5FCSXCxcITvd4l{KEG|c3H5 MkT4NE0yPSEQvF2= MlToNlQhcA>? MULpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? M1H0NFIzOThyM{C4
Huh-7 MV;BdI9xfG:|aYOgRZN{[Xl? NIDKVlMxNTF3IN88US=> NGnZdlQzPCCq NHLKdYFqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= Mo\MNlIyQDB|MEi=
PLC5 NXP5S5FLTnWwY4Tpc44hSXO|YYm= MlfkNE0yOCEQvF2= Ml;BNlQhcA>? MXzjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> Mk\aNlIyQDB|MEi=
Hep3B MnTkSpVv[3Srb36gRZN{[Xl? Mn3INE0yOCEQvF2= NUm5end5OjRiaB?= NVroWVNm[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w MnOxNlIyQDB|MEi=
Sk-Hep1 MoDPSpVv[3Srb36gRZN{[Xl? M{HGUlAuOTBizszN MkjUNlQhcA>? M1:3NINifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? M2nQO|IzOThyM{C4
Huh-7 MUfGeY5kfGmxbjDBd5NigQ>? MmPsNE0yOCEQvF2= NXjkcIllOjRiaB?= Mk[wZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v MUeyNlE5ODNyOB?=
SW780 NWH4cYNoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUm1JIQ> NUHoRm1mUUN3ME21NEBvVQ>? MkS2NlEyOTl4NkG=
RT112 MnnSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1vuZ|Uh\A>? MkLiTWM2OD1zNTDuUS=> MUWyNVEyQTZ4MR?=
RT4 NXvyNJNMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEK3OnA2KGR? NHmwVFZKSzVyPUWgcm0> M2roPVIyOTF7Nk[x
JMSU1 NGrveZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVK1JIQ> M1\1VmlEPTB;NUCgcm0> NVPibZZ6OjFzMUm2OlE>
J82 MlTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHzkcG42KGR? MVjJR|UxRTF2MECgcm0> NIHrcnUzOTFzOU[2NS=>
97-7 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWS1JIQ> M32wbWlEPTB;MUCwNEBvVQ>? M4nnOVIyOTF7Nk[x
RT112 NUX2N2R4TnWwY4Tpc44hSXO|YYm= MkntOVAxKG6P M3XFcFI1KGh? NYDjV|IxcW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz M360SVIyOTF7Nk[x
RT4 NIXnUGZHfW6ldHnvckBCe3OjeR?= NUjI[YxoPTByIH7N Mn\YNlQhcA>? NUS3e3M2cW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz M1mzOFIyOTF7Nk[x
MGH-U3 MVnGeY5kfGmxbjDBd5NigQ>? NGX0NXM2ODBibl2= NUX1Zoc3OjRiaB?= MYfpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? MWeyNVEyQTZ4MR?=
SW780 MkHxSpVv[3Srb36gRZN{[Xl? MWG1NFAhdk1? Mk\4NlQhcA>? NH3zO21qdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= NWCxVYZHOjFzMUm2OlE>
97-7 MlzsSpVv[3Srb36gRZN{[Xl? M330dFUxOCCwTR?= MkjuNlQhcA>? M3LPWolv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= M2HTdlIyOTF7Nk[x
 J807C M2LGW2NmdGxiVnnhZoltcXS7IFHzd4F6 MW[wMVQxOCCwTR?= NH3zWJc1QCCq M4KyfYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MlPsNVU2QTh6MUS=
Y373C MYrD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NX:wNVhyOC12MECgcm0> MX60PEBp MnzabY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> Ml3mNVU2QTh6MUS=
K650E NGrHeHNE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVPmNVdZOC12MECgcm0> NUjHWmk6PDhiaB?= M1jkU4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MUWxOVU6QDhzNB?=
G384D NV;0VZBmS2WubDDWbYFjcWyrdImgRZN{[Xl? MXqwMVQxOCCwTR?= M3P3fFQ5KGh? NGDpT|ZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MkX6NVU2QTh6MUS=
F384L NF\HPHBE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NHfJcHAxNTRyMDDuUS=> NWPvUHB1PDhiaB?= MYTpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M3LMT|E2PTl6OEG0
KMS11 NF7EUVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojMO|IhcA>? M13obWlEPTB;OUCgcm0> NIT1VXUyPTV7OEixOC=>
KMS18 MoS4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH;4WFg4OiCq M3L6[GlEPTB;NUWwJI5O NXvpPJRnOTV3OUi4NVQ>
OPM2 MoTBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUPOTGM5PzJiaB?= MkXGTWM2OD17MDDuUS=> NV[yRWtFOTV3OUi4NVQ>
H929 NHLObVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHETIFjPzJiaB?= M{mxPWlEPTB-IEK1NFAhdk1? NEX0Z2MyPTV7OEixOC=>
8226 NYrWTXFDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPJPI04OiCq MYTJR|UxRiB{NUCwJI5O NYPld2pYOTV3OUi4NVQ>
U266 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGrpb4g4OiCq Mo\CTWM2OD5iMkWwNEBvVQ>? MYKxOVU6QDhzNB?=

... 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]
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  • 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.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID