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 NFrVdIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTBwNES5JO69VQ>? M2Kz[VI2OjB{MEez
SupB15-R MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWPJR|UxRTBwNUW4JO69VQ>? MXqyOVIxOjB5Mx?=
BaF3-pSRα MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3HYW2lEPTB;MD62Olgh|ryP NGLle2gzPTJyMkC3Ny=>
BaF3-p210Bcr-Abl MoW5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWTJR|UxRTBwNkmyJO69VQ>? MlTQNlUzODJyN{O=
BaF3-p210Bcr-Abl-T315I NXfHfWZQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH3BN3dKSzVyPUKuOlI3KM7:TR?= MY[yOVIxOjB5Mx?=
CCRF-CEM NHfwV5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn3OTWM2OD1yLkO5PEDPxE1? NYTVXFVvOjV{MEKwO|I>
CEM/C2 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTFwMUK1JO69VQ>? NWHOUIVQOjV{MEKwO|I>
Nalm-6 NGnXSndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYPJR|UxRTBwM{iyJO69VQ>? NWD3VnhSOjV{MEKwO|I>
SEM-K2 NF;OdWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPyOJBKSzVyPUCuNFIzKM7:TR?= NWO2VWtsOjV{MEKwO|I>
HB-1119 MkHyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3rvW2lEPTB;MD6wNlgh|ryP MmXjNlUzODJyN{K=
RS4:11 NULXeIF5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPBc|A6UUN3ME2yMlgyKM7:TR?= M2LMPFI2OjB{MEey
Nalm-6 NH7tfnlCeG:ydH;zbZMhSXO|YYm= NWHYbIZvOiEQvF2= Mk\vNlQwPDhiaB?= Mnf4bY5lfWOnczDhdI9xfG:|aYOgdoV{fWy2aX7nJIlvKGGkb4X0JFczLSCxZjDj[YxtKGSnYYToJIFnfGW{IEK0JIghfHKnYYTt[Y51KGGwZDC4NUUh[W[2ZYKgOFghcA>? MlOyNlUzODJyN{K=
SEM-K2 MkT2RZBweHSxc3nzJGF{e2G7 MofVNE4yNzFizszN NEfpfo8zPCCq MofWbY5lfWOnczDlZZJtgSCjcH;weI9{cXNib3[gV2VONUt{IHPlcIx{KGG2IECuNUDPxE1iYX\0[ZIhOjRiaB?= NXfTTmVwOjV{MEKwO|I>
HCT-116 NH[4eHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYDVeWNTUUN3ME2zMlA2OC53ODFOwG0> NV7wO|RbOjR2OUW3OVA>
HT-29 NGjZd3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1\jfmlEPTB;NT6yNU46OyEQvF2= MXKyOFQ6PTd3MB?=
SW-480 NFr4[FBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmK1TWM2OD12LkOzNE41PyEQvF2= M{LLVlI1PDl3N{Ww
CaCO2 NHn1eW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLoTWM2OD1|LkKzNE43PCEQvF2= M4T2N|I1PDl3N{Ww
LS174T M3vMe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4W2UWlEPTB;ND6zN|AvPDdizszN NWTkU2cxOjR2OUW3OVA>
HEC-1A MWLGeY5kfGmxbjDBd5NigQ>? MkLtNE4xPS9yLkGvNE42KM7:TR?= NY\CU4tXPzJiaB?= MVHjZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> MlKzNlQ1QTV5NUC=
AN3CA MnezSpVv[3Srb36gRZN{[Xl? NYHZOVdLOC5yNT:wMlEwOC53IN88US=> MVG3NkBp NVLI[Glr[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? NFLnS5EzPDR7NUe1NC=>
MFE-296  MoPUSpVv[3Srb36gRZN{[Xl? NUX3cXUxOC5yNT:wMlEwOC53IN88US=> NHG4[IE4OiCq MXvjZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> NU\yN4RROjR2OUW3OVA>
UMC3 Mn\FR4VtdCCYaXHibYxqfHliQYPzZZk> M2LWWFEuOTBizszN NU\wUWZZPzJiaB?= NGeybG1qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NHLoPXMzPDN{NUS2NS=>
5637 Ml7IR4VtdCCYaXHibYxqfHliQYPzZZk> M3TXSFEuOTBizszN M{O5XlczKGh? NGra[mlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NHW3ZmYzPDN{NUS2NS=>
HU456 NVfCWG45S2WubDDWbYFjcWyrdImgRZN{[Xl? M2e1NlEuOTBizszN MlrCO|IhcA>? M1[zNolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz Ml7RNlQ{OjV2NkG=
MGHU4 MV;D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MWCxMVExKM7:TR?= MVq3NkBp NInXNJBqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MlnvNlQ{OjV2NkG=
HT1376 NHLJNVFE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M3HH[VEuOTBizszN MWm3NkBp NV7HdnRDcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MmTCNlQ{OjV2NkG=
RT112 NFHpfHVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NUC3SnI6OS1zMDFOwG0> M1;FVlczKGh? Mo\ZbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M4\NU|I1OzJ3NE[x
T24 NUjhRWRvS2WubDDWbYFjcWyrdImgRZN{[Xl? NX;lcpR1OS1zMDFOwG0> MkfxO|IhcA>? M1Hw[olvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M2XlPVI1OzJ3NE[x
BFTC905 NFnxcmdE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVnmbGlwOS1zMDFOwG0> NY[4bol6PzJiaB?= MXPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NVvoSmVFOjR|MkW0OlE>
TCC-SUP Mkj0R4VtdCCYaXHibYxqfHliQYPzZZk> M{ftUFEuOTBizszN NX\Ed|lLPzJiaB?= NF3jSXJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NXP1bWdlOjR|MkW0OlE>
RT4 NXXzTYsyS2WubDDWbYFjcWyrdImgRZN{[Xl? MnfMNU0yOCEQvF2= M{\ETVczKGh? NEPDdodqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NH;MVJkzPDN{NUS2NS=>
HONE1 MorHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVvlZndMOC5zLUGwJO69VQ>? NH[yXVI1QMLiaB?= NE\ReHBqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MXGyOFI{QDB7NB?=
HNE1 NVjkR4hPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH3ZWYIxNjFvMUCg{txO MYe0POKhcA>? MV\pcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MXyyOFI{QDB7NB?=
CNE2  M12yXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX3HXmxiOC5zLUGwJO69VQ>? NGDRfHE1QMLiaB?= NXfOcHBucW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NGXXNXUzPDJ|OEC5OC=>
C666-1 NWG2XGxCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlXYNE4yNTFyIN88US=> NGj0b5E1QMLiaB?= NYXOPJJ{cW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NVHsOG0zOjR{M{iwPVQ>
HeLa NEG0eIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXm1d|JnOC5zLUGwJO69VQ>? NYH4XIpXOjRiaB?= NEi0N2tqdmS3Y3XzJGczN01iYYLy[ZN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MkXzNlQzOzhyOUS=
Hep3B NIfjWlFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEH5fFcxNjFvMUCg{txO NYnXUVJUOjRiaB?= NUTyW2xFcW6mdXPld{BIOsLiYYLy[ZN1yqB? MUiyOFI{QDB7NB?=
HepG2 MmDNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYe0PEBp MUjJR|UxRTJwN{K3JOKyKDBwNEK5JO69VQ>? NIX2NVUzOzV2NkW5NS=>
Hep3B NEG3WlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MW[0PEBp NXfxPJZ{UUN3ME20MlIzOyEEsTCwMlg{QSEQvF2= NXO3RWZmOjN3NE[1PVE>
PLC/PRF5 M4rWZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{Dk[VQ5KGh? NFrYPVVKSzVyPUG2MlEzOCEEsTC0MlAxOSEQvF2= NWTufXFuOjN3NE[1PVE>
Huh7 NV35O2t1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4XmTFQ5KGh? NXnPeIdyUUN3ME2xOU4xODdiwsGgO{4{OzRizszN M3vDZlI{PTR4NUmx
HepG2 MliwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoflO|IhcA>? NFPxXndKSzVyPUGuNlAxKMLzIECuNlI3KM7:TR?= NECyWWszOzV2NkW5NS=>
Hep3B NV64dWx1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXzO|IhcA>? MWfJR|UxRTBwOEmyJOKyKDBwMES0JO69VQ>? MWqyN|U1PjV7MR?=
PLC/PRF5 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnLKO|IhcA>? MnzCTWM2OD1|LkGxNEDDuSByLkOzO{DPxE1? M1;KOVI{PTR4NUmx
Huh7 MnPHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVfSdZpKPzJiaB?= M1vieWlEPTB;Mz65PFAhyrFiMD64NFMh|ryP NFjoNXIzOzV2NkW5NS=>
MFE280 NIG4PJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHO5UGFKSzVyPUCuOFIhyrFiMD6wOkDPxE1? NYnOZXdCOjN2NEO4NFU>
AN3CA MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2DTR2lEPTB;MD61NEDDuSByLkGwJO69VQ>? MX2yN|Q1OzhyNR?=
HEC155 M1fYOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTBwNk[gxtEhOC5yOTFOwG0> NGO1d|EzOzR2M{iwOS=>
MFE296 NUfrSFh7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIDnUnFKSzVyPUCuOlYhyrFiMD6xPUDPxE1? Mn3ONlM1PDN6MEW=
SPAC1S MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU\JR|UxRTBwN{egxtEhOC5yODFOwG0> NVnCSoV7OjN2NEO4NFU>
RL952 MkDJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTBwOUOgxtEhOC5yMTFOwG0> MYKyN|Q1OzhyNR?=
EN1 NWDFNIFMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmnFTWM2OD1zLkCyJOKyKDBwMkWg{txO Mlj4NlM1PDN6MEW=
SNGII MlrSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\JTWM2OD1zLkK0JOKyKDBwMkig{txO MoTxNlM1PDN6MEW=
ISHIKAWA MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoTTTWM2OD1zLkOwJOKyKDBwMUGg{txO NGjPS2MzOzR2M{iwOS=>
HEC1A NFHacm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvVTWM2OD1zLkO0JOKyKDBwM{Cg{txO NHO1c2EzOzR2M{iwOS=>
KLE MlKwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkjPTWM2OD1zLkO3JOKyKDBwMEKg{txO MnL0NlM1PDN6MEW=
SNGM MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGPiU5BKSzVyPUGuOFIhyrFiMD6xN{DPxE1? NX:zV3djOjN2NEO4NFU>
USPC2 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4fPVmlEPTB;MT62NkDDuSByLkCxJO69VQ>? NGTUfWgzOzR2M{iwOS=>
EN MnXES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{XlWmlEPTB;MT62OkDDuSByLkCxJO69VQ>? M{PiWFI{PDR|OEC1
MFE319 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jJZmlEPTB;MT64O{DDuSByLkS1JO69VQ>? MUOyN|Q1OzhyNR?=
EFE184 NHf6O21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlH4TWM2OD1{LkC0JOKyKDBwMUOg{txO M1rMUFI{PDR|OEC1
ECC1 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrZcGVKSzVyPUKuNFchyrFiMD6wNUDPxE1? M33SNVI{PDR|OEC1
HEC1B MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn;ETWM2OD1{LkW3JOKyKDBwMkOg{txO MYCyN|Q1OzhyNR?=
USPC1 NVTFd2pDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWXsUZhOUUN3ME2yMlYxKMLzIECuNVMh|ryP M2XZS|I{PDR|OEC1
SPAC1L NEH2NIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGXFcXdKSzVyPUOuNFYhyrFiMT6xOEDPxE1? MWOyN|Q1OzhyNR?=
HUVEC MmnKR4VtdCCYaXHibYxqfHliQYPzZZk> MmrVNE0zPSEQvF2= MXW3NkBp MX;EUXNQ M3LNVolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M2DrW|I{OjJ6MEG3
HMVEC MUfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MUSwMVI2KM7:TR?= MXS3NkBp NGPPS5pFVVOR NXLNbGxmcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NXO0OXFqOjN{MkiwNVc>
MHCC-97H NIH1d|ZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MYiwMVI2KM7:TR?= M4HZNFczKGh? NYXzOXVLTE2VTx?= MlzobY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NULKUZc2OjN{MkiwNVc>
SMMC7721 NVTNOmJQS2WubDDWbYFjcWyrdImgRZN{[Xl? M3nmc|AuOjVizszN M4fzSFczKGh? M1fCOWROW09? MV7pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NVK0b2c5OjN{MkiwNVc>
Huh-7 M12xfmFxd3C2b4Ppd{BCe3OjeR?= NEn5[ngxNTF{LkWg{txO MUiyOEBp M1;2c2ROW00EoB?= MXLz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NYn6VohIOjJ{M{C0O|k>
Sk-Hep1 NIqzR4tCeG:ydH;zbZMhSXO|YYm= M2TGZVAuOTJwNTFOwG0> NH\U[20zPCCq NIrYOoZFVVORwrC= NEjEWYd{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz NFPr[mszOjJ|MES3PS=>
Hep3B M1ryW2Fxd3C2b4Ppd{BCe3OjeR?= NXnOeZF{OC1zMj61JO69VQ>? NVzJ[m5uOjRiaB?= NHfDSYJFVVORwrC= M1fsc5NmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NUDO[JJMOjJ{M{C0O|k>
PLC5 NH\LO|lCeG:ydH;zbZMhSXO|YYm= MkL2NE0yOi53IN88US=> M{nlWVI1KGh? MXfEUXNQyqB? NHLNUWx{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz Mmr6NlIzOzB2N{m=
PLC5 M2fuSWNmdGxiVnnhZoltcXS7IFHzd4F6 Mn\CNE0yPSEQvF2= MkTlO|IhcA>? M3HYbZJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MnvGNlIyQDB|MEi=
Hep3B NWixbIVmS2WubDDWbYFjcWyrdImgRZN{[Xl? M3[3TlAuOTVizszN NWHzT3pMPzJiaB?= NEPMPHdz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NUDVOXZYOjJzOECzNFg>
Sk-Hep1 NXnsSnBnS2WubDDWbYFjcWyrdImgRZN{[Xl? M{D3c|AuOTVizszN NIf3bpY4OiCq M{jZW5Jm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NXLw[4VMOjJzOECzNFg>
Huh-7 NYXpd3pOS2WubDDWbYFjcWyrdImgRZN{[Xl? M4\lXlAuOTVizszN NVPEZ4V[PzJiaB?= MoDodoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MoC1NlIyQDB|MEi=
PLC5 MljqRZBweHSxc3nzJGF{e2G7 NWniTZEzOC1zNTFOwG0> MUCyOEBp MlPibY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MWGyNlE5ODNyOB?=
Hep3B M2\EUWFxd3C2b4Ppd{BCe3OjeR?= M{fQTFAuOTVizszN NXTWUZRPOjRiaB?= MVnpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? NH\XcWQzOjF6MEOwPC=>
Sk-Hep1 MWjBdI9xfG:|aYOgRZN{[Xl? M2rvOFAuOTVizszN NVHsS4tuOjRiaB?= M4DMeIlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi Mn3kNlIyQDB|MEi=
Huh-7 MYnBdI9xfG:|aYOgRZN{[Xl? NWj0VZBwOC1zNTFOwG0> MkHJNlQhcA>? NXfBO45NcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NG\kdJczOjF6MEOwPC=>
PLC5 MX;GeY5kfGmxbjDBd5NigQ>? NXjmUpdEOC1zMDFOwG0> MX2yOEBp NWT4ZpNn[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w Mme0NlIyQDB|MEi=
Hep3B MljpSpVv[3Srb36gRZN{[Xl? NEnyeXMxNTFyIN88US=> NFX5Z5EzPCCq M3jvboNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? NIjGPHAzOjF6MEOwPC=>
Sk-Hep1 MYLGeY5kfGmxbjDBd5NigQ>? MWqwMVExKM7:TR?= MX2yOEBp MXfjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> MVOyNlE5ODNyOB?=
Huh-7 MW\GeY5kfGmxbjDBd5NigQ>? M17Sd|AuOTBizszN NILkNJAzPCCq M3[3bYNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? M2DSUlIzOThyM{C4
SW780 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{jLWFUh\A>? NIGyV3VKSzVyPUWwJI5O NFLRcoczOTFzOU[2NS=>
RT112 NFj3d2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1GzeVUh\A>? M2j0N2lEPTB;MUWgcm0> MXSyNVEyQTZ4MR?=
RT4 Mnz3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2LifVUh\A>? Ml;JTWM2OD13IH7N MY[yNVEyQTZ4MR?=
JMSU1 M2e4N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXlZ4Y2KGR? MVTJR|UxRTVyIH7N NYX3UnpvOjFzMUm2OlE>
J82 M3voTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{jMN|Uh\A>? MlLMTWM2OD1zNECwJI5O MUGyNVEyQTZ4MR?=
97-7 MoTpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYG1JIQ> MmnsTWM2OD1zMECwJI5O M17iU|IyOTF7Nk[x
RT112 NV\tNINRTnWwY4Tpc44hSXO|YYm= NFnoUGM2ODBibl2= NF3LNXkzPCCq NGLze4pqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MnK1NlEyOTl4NkG=
RT4 NV;sU3RkTnWwY4Tpc44hSXO|YYm= MnrLOVAxKG6P MljqNlQhcA>? MmrubY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NIjWTokzOTFzOU[2NS=>
MGH-U3 MorISpVv[3Srb36gRZN{[Xl? NV7mTZdUPTByIH7N MmXZNlQhcA>? MXPpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NFn5TZYzOTFzOU[2NS=>
SW780 M1HDUGZ2dmO2aX;uJGF{e2G7 MoLuOVAxKG6P MnrSNlQhcA>? NYDnZndScW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz NH;j[5czOTFzOU[2NS=>
97-7 NXPZRpd1TnWwY4Tpc44hSXO|YYm= M1XleVUxOCCwTR?= M2m1N|I1KGh? MV3pcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NFTZTY0zOTFzOU[2NS=>
 J807C NV3UWnZnS2WubDDWbYFjcWyrdImgRZN{[Xl? NUXFb3pxOC12MECgcm0> MUS0PEBp MUnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NHHFcVMyPTV7OEixOC=>
Y373C M{TkWGNmdGxiVnnhZoltcXS7IFHzd4F6 M4TtZ|AuPDByIH7N MYC0PEBp MV\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NGPIVFIyPTV7OEixOC=>
K650E NHHDUnpE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M3TDOFAuPDByIH7N MlvUOFghcA>? NYXrSoROcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NYXEZ3NTOTV3OUi4NVQ>
G384D MX;D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NXfreWJTOC12MECgcm0> MnXxOFghcA>? NY\HRndwcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NY\EPVg6OTV3OUi4NVQ>
F384L M37jSmNmdGxiVnnhZoltcXS7IFHzd4F6 MkHQNE01ODBibl2= NUHy[XhnPDhiaB?= MnXEbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MVexOVU6QDhzNB?=
KMS11 MkL2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfEdppoPzJiaB?= M2nTSWlEPTB;OUCgcm0> NEDNWVQyPTV7OEixOC=>
KMS18 NF\HNpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYW3NkBp MXrJR|UxRTV3MDDuUS=> MXKxOVU6QDhzNB?=
OPM2 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXm3NkBp M1zGTWlEPTB;OUCgcm0> Mlz6NVU2QTh6MUS=
H929 NEjrR3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NInCU4c4OiCq NF;idJVKSzVyPjCyOVAxKG6P MkT0NVU2QTh6MUS=
8226 M2Dmb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXS3NkBp NIq5T29KSzVyPjCyOVAxKG6P NFLzbZcyPTV7OEixOC=>
U266 M3vmWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXK3NkBp M1XVV2lEPTB-IEK1NFAhdk1? NWnMS2JbOTV3OUi4NVQ>

... 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]
+ Expand

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