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
USD 170 In stock
USD 270 In stock
USD 470 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

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

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 M33PWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVP0dmJ4UUN3ME2wMlQ1QSEQvF2= NGXpUnQzPTJyMkC3Ny=>
SupB15-R Mn\oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{jDeGlEPTB;MD61OVgh|ryP MXOyOVIxOjB5Mx?=
BaF3-pSRα MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTBwNk[4JO69VQ>? MojwNlUzODJyN{O=
BaF3-p210Bcr-Abl M1mxXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFnBWlRKSzVyPUCuOlkzKM7:TR?= MYOyOVIxOjB5Mx?=
BaF3-p210Bcr-Abl-T315I M1[1XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{TKXWlEPTB;Mj62NlYh|ryP NH\UOmIzPTJyMkC3Ny=>
CCRF-CEM MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoG1TWM2OD1yLkO5PEDPxE1? MXSyOVIxOjB5Mh?=
CEM/C2 NXK1UJRFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2PsdGlEPTB;MT6xNlUh|ryP MWqyOVIxOjB5Mh?=
Nalm-6 NHfyRolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3vGcmlEPTB;MD6zPFIh|ryP MYKyOVIxOjB5Mh?=
SEM-K2 NILtbYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\xTWM2OD1yLkCyNkDPxE1? NU\FXpZsOjV{MEKwO|I>
HB-1119 M33Mfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHKzRVNKSzVyPUCuNFI5KM7:TR?= NXrVNIFlOjV{MEKwO|I>
RS4:11 NFrBWWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\kTWM2OD1{LkixJO69VQ>? Mn24NlUzODJyN{K=
Nalm-6 M4Ds[WFxd3C2b4Ppd{BCe3OjeR?= NY\MV|BsOiEQvF2= M2LiclI1NzR6IHi= NH[5TJFqdmS3Y3XzJIFxd3C2b4Ppd{Bz\XO3bITpcochcW5iYXLveZQhPzJnIH;mJINmdGxiZHXheIgh[W[2ZYKgNlQhcCC2cnXheI1mdnRiYX7kJFgyLSCjZoTldkA1QCCq MlfXNlUzODJyN{K=
SEM-K2 M4Sy[2Fxd3C2b4Ppd{BCe3OjeR?= NVTodWF6OC5zL{Gg{txO MVGyOEBp NFvtRlBqdmS3Y3XzJIViemy7IHHwc5B1d3OrczDv[kBUTU1vS{KgZ4VtdHNiYYSgNE4yKM7:TTDh[pRmeiB{NDDo M{\aSVI2OjB{MEey
HCT-116 M1jMVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYXJR|UxRTNwMEWwMlU5KM7:TR?= MmDhNlQ1QTV5NUC=
HT-29 M1raeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnTUTWM2OD13LkKxMlk{KM7:TR?= MorKNlQ1QTV5NUC=
SW-480 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LwS2lEPTB;ND6zN|AvPDdizszN NXfCSGFsOjR2OUW3OVA>
CaCO2 NHPkRlFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvxTWM2OD1|LkKzNE43PCEQvF2= NG\wc3ozPDR7NUe1NC=>
LS174T NUXDbYN3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmrzTWM2OD12LkOzNE41PyEQvF2= NFjsVWMzPDR7NUe1NC=>
HEC-1A M3PZOWZ2dmO2aX;uJGF{e2G7 NID0WosxNjB3L{CuNU8xNjVizszN M1XEfVczKGh? NIfpN3hk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? NUTtRZhDOjR2OUW3OVA>
AN3CA NV60VWdVTnWwY4Tpc44hSXO|YYm= NVvXOoJIOC5yNT:wMlEwOC53IN88US=> MnjPO|IhcA>? M2f0O4NifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v NUTWVG5FOjR2OUW3OVA>
MFE-296  NFPNUI1HfW6ldHnvckBCe3OjeR?= NH\pUoUxNjB3L{CuNU8xNjVizszN NFf4WlM4OiCq NGrPXFJk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? M17PWVI1PDl3N{Ww
UMC3 NWHRRXFuS2WubDDWbYFjcWyrdImgRZN{[Xl? MUixMVExKM7:TR?= NX30b4Q3PzJiaB?= NWHGZY1KcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NWrUcZRyOjR|MkW0OlE>
5637 M1fpXWNmdGxiVnnhZoltcXS7IFHzd4F6 M2XLZVEuOTBizszN MkPBO|IhcA>? MlnPbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MlXYNlQ{OjV2NkG=
HU456 MYfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3fpVVEuOTBizszN NHXMNFU4OiCq MVLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NF7OXJUzPDN{NUS2NS=>
MGHU4 NYnkWnd2S2WubDDWbYFjcWyrdImgRZN{[Xl? NEi3TWMyNTFyIN88US=> NFTFPGs4OiCq MYPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MlrQNlQ{OjV2NkG=
HT1376 MXTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NFnXO2kyNTFyIN88US=> M3Xac|czKGh? M2TIW4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NXTlfZc6OjR|MkW0OlE>
RT112 NYLjd5h[S2WubDDWbYFjcWyrdImgRZN{[Xl? NGnhSJEyNTFyIN88US=> M4HQXFczKGh? M4[4SIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NXe2W4lSOjR|MkW0OlE>
T24 Mnv2R4VtdCCYaXHibYxqfHliQYPzZZk> MmnuNU0yOCEQvF2= NV\ZdY5pPzJiaB?= M4rSU4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NYn3Omx1OjR|MkW0OlE>
BFTC905 M3O2bGNmdGxiVnnhZoltcXS7IFHzd4F6 MlO3NU0yOCEQvF2= MX:3NkBp NIDQSplqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M1PiN|I1OzJ3NE[x
TCC-SUP MXXD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NVXifpk{OS1zMDFOwG0> NXvCUWpKPzJiaB?= M2KxfolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MoPYNlQ{OjV2NkG=
RT4 MV\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NI\lenEyNTFyIN88US=> NF6zdII4OiCq MXrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MUOyOFMzPTR4MR?=
HONE1 NVnDO|d5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXLb3F1OC5zLUGwJO69VQ>? NUjRcnRiPDkEoHi= NXPsenM{cW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M2HoWVI1OjN6MEm0
HNE1 NEjkdmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWCwMlEuOTBizszN MljqOFjDqGh? Mn;3bY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy MlLJNlQzOzhyOUS=
CNE2  MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkK5NE4yNTFyIN88US=> MYW0POKhcA>? MlP4bY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy M{XF[lI1OjN6MEm0
C666-1 M3LTVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVGwMlEuOTBizszN NHrBXWc1QMLiaB?= M2TkOIlv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NYTvUG42OjR{M{iwPVQ>
HeLa NWTYdIhRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXWwMlEuOTBizszN NXHzOFB7OjRiaB?= NUjFe5RqcW6mdXPld{BIOi:PIHHydoV{fCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M1\HWVI1OjN6MEm0
Hep3B MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX6wMlEuOTBizszN NF\UXZMzPCCq M1W1b4lv\HWlZYOgS|LDqGG{cnXzeOKh MUOyOFI{QDB7NB?=
HepG2 M1PEZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPtOFghcA>? NVfZU5hGUUN3ME2yMlczPyEEsTCwMlQzQSEQvF2= NWXNbGtIOjN3NE[1PVE>
Hep3B NH7GUXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUjyR4tRPDhiaB?= NF3RSJRKSzVyPUSuNlI{KMLzIECuPFM6KM7:TR?= NVfHZoJiOjN3NE[1PVE>
PLC/PRF5 NGD6WpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{KwfVQ5KGh? Mle0TWM2OD1zNj6xNlAhyrFiND6wNFEh|ryP Mn2xNlM2PDZ3OUG=
Huh7 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWG0PEBp M1XiN2lEPTB;MUWuNFA4KMLzIEeuN|M1KM7:TR?= MoLVNlM2PDZ3OUG=
HepG2 M3LUUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlX4O|IhcA>? M4\jTWlEPTB;MT6yNFAhyrFiMD6yNlYh|ryP NHz5[YEzOzV2NkW5NS=>
Hep3B M3TnWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYm3NkBp Ml60TWM2OD1yLki5NkDDuSByLkC0OEDPxE1? NXniN3BIOjN3NE[1PVE>
PLC/PRF5 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV23NkBp NULFWZhNUUN3ME2zMlEyOCEEsTCwMlM{PyEQvF2= NGjTOVMzOzV2NkW5NS=>
Huh7 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MofQO|IhcA>? M4WxbmlEPTB;Mz65PFAhyrFiMD64NFMh|ryP M{nxfFI{PTR4NUmx
MFE280 NEO2TWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE[2cYtKSzVyPUCuOFIhyrFiMD6wOkDPxE1? MmDwNlM1PDN6MEW=
AN3CA MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXfJR|UxRTBwNUCgxtEhOC5zMDFOwG0> NFPucFMzOzR2M{iwOS=>
HEC155 NV64OGltT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnm4TWM2OD1yLk[2JOKyKDBwMEmg{txO NYDWR5FEOjN2NEO4NFU>
MFE296 MmPWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmfwTWM2OD1yLk[2JOKyKDBwMUmg{txO NWD1VZRMOjN2NEO4NFU>
SPAC1S NVTmdFR4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVWwN3hrUUN3ME2wMlc4KMLzIECuNFgh|ryP NUfWSGh[OjN2NEO4NFU>
RL952 NFzwdYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGDUWY9KSzVyPUCuPVMhyrFiMD6wNUDPxE1? MV2yN|Q1OzhyNR?=
EN1 NHrRNFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1HPPWlEPTB;MT6wNkDDuSByLkK1JO69VQ>? NVT0TGNSOjN2NEO4NFU>
SNGII M3PRXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3\CTmlEPTB;MT6yOEDDuSByLkK4JO69VQ>? MofVNlM1PDN6MEW=
ISHIKAWA NETWN5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mo\zTWM2OD1zLkOwJOKyKDBwMUGg{txO MmDLNlM1PDN6MEW=
HEC1A NFyzXJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWnJR|UxRTFwM{SgxtEhOC5|MDFOwG0> MlzINlM1PDN6MEW=
KLE MnjZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFK3eYNKSzVyPUGuN|chyrFiMD6wNkDPxE1? NFv1WnkzOzR2M{iwOS=>
SNGM NXT1XnM{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDqc2ZjUUN3ME2xMlQzKMLzIECuNVMh|ryP MW[yN|Q1OzhyNR?=
USPC2 NVzFcWdHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2LINmlEPTB;MT62NkDDuSByLkCxJO69VQ>? MVGyN|Q1OzhyNR?=
EN MmfvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTFwNk[gxtEhOC5yMTFOwG0> NYr5eWlEOjN2NEO4NFU>
MFE319 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHEPYlGUUN3ME2xMlg4KMLzIECuOFUh|ryP M4HDfFI{PDR|OEC1
EFE184 NILMN4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXzRd21DUUN3ME2yMlA1KMLzIECuNVMh|ryP MoHCNlM1PDN6MEW=
ECC1 M1mzWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE\abVhKSzVyPUKuNFchyrFiMD6wNUDPxE1? MVWyN|Q1OzhyNR?=
HEC1B NGTwbo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTJwNUegxtEhOC5{MzFOwG0> MVSyN|Q1OzhyNR?=
USPC1 NWPYXZhmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVvhdFVSUUN3ME2yMlYxKMLzIECuNVMh|ryP Mk[4NlM1PDN6MEW=
SPAC1L M4m5dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NILEVmdKSzVyPUOuNFYhyrFiMT6xOEDPxE1? MWGyN|Q1OzhyNR?=
HUVEC MYLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MknsNE0zPSEQvF2= MnHxO|IhcA>? NE\UZpdFVVOR M4PTNIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MYWyN|IzQDBzNx?=
HMVEC MUfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1X1UFAuOjVizszN NG\jbJg4OiCq MmrISG1UVw>? NGTrRphqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NH7ST2UzOzJ{OECxOy=>
MHCC-97H NUe1VVU3S2WubDDWbYFjcWyrdImgRZN{[Xl? MWCwMVI2KM7:TR?= M1O2SlczKGh? MW\EUXNQ Mn7xbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M1\4O|I{OjJ6MEG3
SMMC7721 NV;rbXh[S2WubDDWbYFjcWyrdImgRZN{[Xl? NIn5b2kxNTJ3IN88US=> NITpU3g4OiCq MUPEUXNQ NH3VXplqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NWHoXlRQOjN{MkiwNVc>
Huh-7 NXzmcm1JSXCxcITvd4l{KEG|c3H5 M1;q[VAuOTJwNTFOwG0> M4HQW|I1KGh? NG\qPYJFVVORwrC= NH;Rd45{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz MV[yNlI{ODR5OR?=
Sk-Hep1 MYHBdI9xfG:|aYOgRZN{[Xl? NIPFbm0xNTF{LkWg{txO NYjsNHdROjRiaB?= NWLtXnZRTE2VT9Mg NXfjfVZwe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NUmyTFBuOjJ{M{C0O|k>
Hep3B MUHBdI9xfG:|aYOgRZN{[Xl? M2LTZ|AuOTJwNTFOwG0> MVqyOEBp M4rjbWROW00EoB?= MlPvd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NXH2UYV5OjJ{M{C0O|k>
PLC5 M{\hemFxd3C2b4Ppd{BCe3OjeR?= M12zNVAuOTJwNTFOwG0> NVnLTFZuOjRiaB?= NV\0XGxUTE2VT9Mg M4HhO5NmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NGPqVFQzOjJ|MES3PS=>
PLC5 NEn4cVBE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MVGwMVE2KM7:TR?= NGLNNpI4OiCq NVj3bm9lemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg MmnjNlIyQDB|MEi=
Hep3B MVrD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MXGwMVE2KM7:TR?= M{P2VVczKGh? NHm0PHJz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NYfWfWliOjJzOECzNFg>
Sk-Hep1 MUHD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MYGwMVE2KM7:TR?= M1Kwc|czKGh? MmXndoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MXiyNlE5ODNyOB?=
Huh-7 NW[2fXJOS2WubDDWbYFjcWyrdImgRZN{[Xl? NIjPXJgxNTF3IN88US=> NX;uOnJqPzJiaB?= Mln2doVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NVHKcoQzOjJzOECzNFg>
PLC5 MYfBdI9xfG:|aYOgRZN{[Xl? NUW4dW9POC1zNTFOwG0> M2XycVI1KGh? NYTPN5lqcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NHXiXoozOjF6MEOwPC=>
Hep3B MmLLRZBweHSxc3nzJGF{e2G7 MYiwMVE2KM7:TR?= MWeyOEBp NGC2VVRqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MYWyNlE5ODNyOB?=
Sk-Hep1 NUGxUJFTSXCxcITvd4l{KEG|c3H5 NIHicHoxNTF3IN88US=> NWXYb3duOjRiaB?= M3LZWIlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NYrhT5JqOjJzOECzNFg>
Huh-7 Mn\2RZBweHSxc3nzJGF{e2G7 NVS1fYtGOC1zNTFOwG0> NHryZVgzPCCq NUftXHFlcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NFjjcHIzOjF6MEOwPC=>
PLC5 NEH3enVHfW6ldHnvckBCe3OjeR?= M3rpelAuOTBizszN NHnQ[ZAzPCCq NYTFdHZ[[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w MmTZNlIyQDB|MEi=
Hep3B M{nKbWZ2dmO2aX;uJGF{e2G7 M4PMdFAuOTBizszN NVHv[4pROjRiaB?= MW\jZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> MXiyNlE5ODNyOB?=
Sk-Hep1 NIjmZphHfW6ldHnvckBCe3OjeR?= NH\sW4kxNTFyIN88US=> MV:yOEBp MVzjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> MXWyNlE5ODNyOB?=
Huh-7 Mmf3SpVv[3Srb36gRZN{[Xl? M3LpcFAuOTBizszN MUCyOEBp NVnJ[2Zv[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w MXeyNlE5ODNyOB?=
SW780 NFf5TVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvLOUBl NVGye2R2UUN3ME21NEBvVQ>? NYrXZlFtOjFzMUm2OlE>
RT112 NEflfHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3XPWlUh\A>? NWrxWpRPUUN3ME2xOUBvVQ>? MoH5NlEyOTl4NkG=
RT4 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlX2OUBl NYD0d5pQUUN3ME21JI5O NX76[m1TOjFzMUm2OlE>
JMSU1 NHnNR|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF\HfnM2KGR? MYnJR|UxRTVyIH7N NF\1dY0zOTFzOU[2NS=>
J82 NFfDcHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLEOUBl NVjtTpI2UUN3ME2xOFAxKG6P NH3pVZczOTFzOU[2NS=>
97-7 NIfFeZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVG1JIQ> MXvJR|UxRTFyMECgcm0> NGPzO2EzOTFzOU[2NS=>
RT112 M{nvXGZ2dmO2aX;uJGF{e2G7 NXO4UFJvPTByIH7N M2KwfFI1KGh? MUjpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? MojTNlEyOTl4NkG=
RT4 M4\0UmZ2dmO2aX;uJGF{e2G7 M1K0[|UxOCCwTR?= MW[yOEBp Mnm5bY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NIX1doIzOTFzOU[2NS=>
MGH-U3 MYDGeY5kfGmxbjDBd5NigQ>? MmjOOVAxKG6P NGHMT|EzPCCq NIDVNZVqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MYCyNVEyQTZ4MR?=
SW780 NGPIVWtHfW6ldHnvckBCe3OjeR?= NVrnenRNPTByIH7N NWH5bZExOjRiaB?= MoTubY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| M2DVWFIyOTF7Nk[x
97-7 NETGRlhHfW6ldHnvckBCe3OjeR?= NWjnVWltPTByIH7N MlLMNlQhcA>? M{TYWIlv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= Mn3PNlEyOTl4NkG=
 J807C M3yySWNmdGxiVnnhZoltcXS7IFHzd4F6 NUDufGE{OC12MECgcm0> MnnoOFghcA>? NH;wW41qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M3f0ZVE2PTl6OEG0
Y373C MYfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MWSwMVQxOCCwTR?= NVP3VI1HPDhiaB?= NUmxd4FmcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M3S4blE2PTl6OEG0
K650E NYHmTHJCS2WubDDWbYFjcWyrdImgRZN{[Xl? M2jNXVAuPDByIH7N MV:0PEBp MV7pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> Mn7JNVU2QTh6MUS=
G384D NYC5Z2RDS2WubDDWbYFjcWyrdImgRZN{[Xl? MYSwMVQxOCCwTR?= NYPtPWw1PDhiaB?= NFHGdIlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MojGNVU2QTh6MUS=
F384L M2TuVWNmdGxiVnnhZoltcXS7IFHzd4F6 Mkn0NE01ODBibl2= NXjlenJHPDhiaB?= MUnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NUXYWGoyOTV3OUi4NVQ>
KMS11 NHvGUo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVi0NnV1PzJiaB?= M2DGOmlEPTB;OUCgcm0> NETvZoEyPTV7OEixOC=>
KMS18 NF\p[5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\WO|IhcA>? Mn3vTWM2OD13NUCgcm0> NGTY[lgyPTV7OEixOC=>
OPM2 NV3UV3ZWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{H4dFczKGh? MnHSTWM2OD17MDDuUS=> NIG4NVEyPTV7OEixOC=>
H929 NYTVbVJ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfy[Ww4OiCq M4jqZWlEPTB-IEK1NFAhdk1? MoHRNVU2QTh6MUS=
8226 NIjZU4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\IO|IhcA>? MoTlTWM2OD5iMkWwNEBvVQ>? M2TvTVE2PTl6OEG0
U266 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{DPNlczKGh? NInrOpFKSzVyPjCyOVAxKG6P M{jVNlE2PTl6OEG0

... 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
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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
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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
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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 <1 mg/mL
Ethanol <1 mg/mL
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* 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
in solvent
Synonyms N/A

Bio Calculators

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
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 Active, not recruiting 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
NCT01972750 Active, not recruiting First or Second Recurrence of Glioblastoma PD Dr. Martin Glas|University Hospital, Bonn October 2013 Phase 1

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