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 M1;BUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1ThXGlEPTB;MD60OFkh|ryP MVqyOVIxOjB5Mx?=
SupB15-R NHrodmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXTJR|UxRTBwNUW4JO69VQ>? NIPnZmgzPTJyMkC3Ny=>
BaF3-pSRα MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY\JR|UxRTBwNk[4JO69VQ>? M1jJ[FI2OjB{MEez
BaF3-p210Bcr-Abl MoDJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoryTWM2OD1yLk[5NkDPxE1? M{DC[|I2OjB{MEez
BaF3-p210Bcr-Abl-T315I NFTFeo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVT1WlJoUUN3ME2yMlYzPiEQvF2= M17pfFI2OjB{MEez
CCRF-CEM NISyc2ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\ZTo1KSzVyPUCuN|k5KM7:TR?= NFrlTogzPTJyMkC3Ni=>
CEM/C2 MlOyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHr0SZVKSzVyPUGuNVI2KM7:TR?= NFLKNI0zPTJyMkC3Ni=>
Nalm-6 NEDRS|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVyyXHB7UUN3ME2wMlM5OiEQvF2= M3XKclI2OjB{MEey
SEM-K2 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXnwUHZFUUN3ME2wMlAzOiEQvF2= MlfnNlUzODJyN{K=
HB-1119 NIjTeGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGrYRXpKSzVyPUCuNFI5KM7:TR?= M3XLdVI2OjB{MEey
RS4:11 NESycHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\o[5NKSzVyPUKuPFEh|ryP NGSxTVkzPTJyMkC3Ni=>
Nalm-6 NXTKOFRxSXCxcITvd4l{KEG|c3H5 MkLtNkDPxE1? MnfJNlQwPDhiaB?= MVPpcoR2[2W|IHHwc5B1d3OrczDy[ZN2dHSrbnegbY4h[WKxdYSgO|ImKG:oIHPlcIwh\GWjdHigZYZ1\XJiMkSgbEB1emWjdH3lcpQh[W6mIEixKUBi\nSncjC0PEBp MWCyOVIxOjB5Mh?=
SEM-K2 NYHNeXRXSXCxcITvd4l{KEG|c3H5 NVrPZ5hNOC5zL{Gg{txO MljxNlQhcA>? M2W4XIlv\HWlZYOg[YFzdHliYYDvdJRwe2m|IH;mJHNGVS2NMjDj[YxteyCjdDCwMlEh|ryPIHHmeIVzKDJ2IHi= MknHNlUzODJyN{K=
HCT-116 MlTSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWrJR|UxRTNwMEWwMlU5KM7:TR?= MYeyOFQ6PTd3MB?=
HT-29 Mmf0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MorVTWM2OD13LkKxMlk{KM7:TR?= NWjIc|V[OjR2OUW3OVA>
SW-480 M2\VbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrPSpU4UUN3ME20MlM{OC52NzFOwG0> MVKyOFQ6PTd3MB?=
CaCO2 NYnQZmNbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTNwMkOwMlY1KM7:TR?= M4PDdlI1PDl3N{Ww
LS174T MnTMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXvJR|UxRTRwM{OwMlQ4KM7:TR?= M3T3XVI1PDl3N{Ww
HEC-1A M1f1e2Z2dmO2aX;uJGF{e2G7 MlLnNE4xPS9yLkGvNE42KM7:TR?= NEnXOlU4OiCq NEHX[mFk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? M2D2RlI1PDl3N{Ww
AN3CA NXnGeIdXTnWwY4Tpc44hSXO|YYm= M3TpfFAvODVxMD6xM|AvPSEQvF2= M1rRRVczKGh? MkjYZ4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> M{LhWlI1PDl3N{Ww
MFE-296  MXvGeY5kfGmxbjDBd5NigQ>? NEDZNo4xNjB3L{CuNU8xNjVizszN MXu3NkBp M3fsUINifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v Mn2zNlQ1QTV5NUC=
UMC3 MYLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NXfmVI5OOS1zMDFOwG0> M1LpeFczKGh? NFLqVI1qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Ml3hNlQ{OjV2NkG=
5637 NE[4UW1E\WyuIG\pZYJqdGm2eTDBd5NigQ>? MnzyNU0yOCEQvF2= NX3sUnp6PzJiaB?= M3jVbYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NXzjfYs6OjR|MkW0OlE>
HU456 NIPmR5JE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MojKNU0yOCEQvF2= M1znTFczKGh? Mne5bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M3LicFI1OzJ3NE[x
MGHU4 MYHD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1;aelEuOTBizszN MXy3NkBp NV;hOopkcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NEXvPVYzPDN{NUS2NS=>
HT1376 NGfHbJBE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1fiNVEuOTBizszN M2rXclczKGh? NUHXNmw{cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NI\CenMzPDN{NUS2NS=>
RT112 MoL2R4VtdCCYaXHibYxqfHliQYPzZZk> NHK2fosyNTFyIN88US=> NVK0UWw4PzJiaB?= M3vPZYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NF\L[FMzPDN{NUS2NS=>
T24 NFf3XHZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MYWxMVExKM7:TR?= M4jKRlczKGh? MYrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NXq0OodsOjR|MkW0OlE>
BFTC905 M2TXZ2NmdGxiVnnhZoltcXS7IFHzd4F6 MkPqNU0yOCEQvF2= NFX1eZM4OiCq MYfpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MUSyOFMzPTR4MR?=
TCC-SUP MYXD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NIW4[2gyNTFyIN88US=> NF;xOWU4OiCq MYDpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M4rNflI1OzJ3NE[x
RT4 MljZR4VtdCCYaXHibYxqfHliQYPzZZk> M2DLSVEuOTBizszN NHnLUIw4OiCq MmL3bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NXPFd5B{OjR|MkW0OlE>
HONE1 NGjNdIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkPGNE4yNTFyIN88US=> NYe1c3VxPDkEoHi= M4nKbYlv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> Mlz1NlQzOzhyOUS=
HNE1 NGTJT2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIDqSWQxNjFvMUCg{txO NFLufnE1QMLiaB?= NXS2OlY{cW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M4jDdVI1OjN6MEm0
CNE2  MkD6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXvZe|NPOC5zLUGwJO69VQ>? NWPkfIdMPDkEoHi= M2PTbYlv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MWeyOFI{QDB7NB?=
C666-1 M1\jV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX6wMlEuOTBizszN NHvQTlc1QMLiaB?= MnT2bY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy MleyNlQzOzhyOUS=
HeLa MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWKwMlEuOTBizszN M{XYdlI1KGh? M120folv\HWlZYOgS|IwVSCjcoLld5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MWeyOFI{QDB7NB?=
Hep3B MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjKb3UxNjFvMUCg{txO NWHlVmxbOjRiaB?= NGf0TW1qdmS3Y3XzJGczyqCjcoLld5TDqA>? MnjINlQzOzhyOUS=
HepG2 MlLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVu0PEBp M3njTWlEPTB;Mj63NlchyrFiMD60Nlkh|ryP M4HHV|I{PTR4NUmx
Hep3B NF3sUpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4nY[|Q5KGh? NFf1dGRKSzVyPUSuNlI{KMLzIECuPFM6KM7:TR?= NYXPUmxlOjN3NE[1PVE>
PLC/PRF5 NEe1cmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVXPPGFbPDhiaB?= NEP1bllKSzVyPUG2MlEzOCEEsTC0MlAxOSEQvF2= MYeyN|U1PjV7MR?=
Huh7 NUnOV21bT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4LDOVQ5KGh? M{W4T2lEPTB;MUWuNFA4KMLzIEeuN|M1KM7:TR?= NIrReFMzOzV2NkW5NS=>
HepG2 M4ezSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnjRO|IhcA>? NV:xdmFCUUN3ME2xMlIxOCEEsTCwMlIzPiEQvF2= NU\oS|FNOjN3NE[1PVE>
Hep3B MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHkO|IhcA>? NV7rZYxPUUN3ME2wMlg6OiEEsTCwMlA1PCEQvF2= NI\JeGYzOzV2NkW5NS=>
PLC/PRF5 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLuZWw2PzJiaB?= NXPCSGhuUUN3ME2zMlEyOCEEsTCwMlM{PyEQvF2= M1XvU|I{PTR4NUmx
Huh7 MlH4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF3qSow4OiCq Ml\pTWM2OD1|Lkm4NEDDuSByLkiwN{DPxE1? Mn;uNlM2PDZ3OUG=
MFE280 NV;0XYdFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTBwNEKgxtEhOC5yNjFOwG0> NWjZUm9COjN2NEO4NFU>
AN3CA MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLQTWM2OD1yLkWwJOKyKDBwMUCg{txO M4C1XlI{PDR|OEC1
HEC155 NX\DZmw2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGnI[HhKSzVyPUCuOlYhyrFiMD6wPUDPxE1? MV2yN|Q1OzhyNR?=
MFE296 M4\zfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX3GfYZCUUN3ME2wMlY3KMLzIECuNVkh|ryP NITHVIYzOzR2M{iwOS=>
SPAC1S NEjXeVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{TSZmlEPTB;MD63O{DDuSByLkC4JO69VQ>? M4nwdlI{PDR|OEC1
RL952 Mo[wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTBwOUOgxtEhOC5yMTFOwG0> MUGyN|Q1OzhyNR?=
EN1 M3vafGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTFwMEKgxtEhOC5{NTFOwG0> M4HXWlI{PDR|OEC1
SNGII MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV7JR|UxRTFwMkSgxtEhOC5{ODFOwG0> MkDUNlM1PDN6MEW=
ISHIKAWA NUf4UFFlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NITDXWlKSzVyPUGuN|AhyrFiMD6xNUDPxE1? NGfrcJIzOzR2M{iwOS=>
HEC1A NE\wfFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHizNZZKSzVyPUGuN|QhyrFiMD6zNEDPxE1? M3j1[FI{PDR|OEC1
KLE NXrIZoJbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXfxT3JIUUN3ME2xMlM4KMLzIECuNFIh|ryP MkXHNlM1PDN6MEW=
SNGM NIXq[IdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX3IVWNEUUN3ME2xMlQzKMLzIECuNVMh|ryP M4n6XFI{PDR|OEC1
USPC2 NXHYd|JlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NE[zeGJKSzVyPUGuOlIhyrFiMD6wNUDPxE1? NI[yeXgzOzR2M{iwOS=>
EN NIDSUZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2LCWmlEPTB;MT62OkDDuSByLkCxJO69VQ>? MlzMNlM1PDN6MEW=
MFE319 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmDrTWM2OD1zLki3JOKyKDBwNEWg{txO NEfYSGUzOzR2M{iwOS=>
EFE184 NIHxZmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonnTWM2OD1{LkC0JOKyKDBwMUOg{txO M3zTVFI{PDR|OEC1
ECC1 Mn\WS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV25VJI2UUN3ME2yMlA4KMLzIECuNFEh|ryP NV:xdnNROjN2NEO4NFU>
HEC1B MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTJwNUegxtEhOC5{MzFOwG0> M3f2b|I{PDR|OEC1
USPC1 NHfqRlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn73TWM2OD1{Lk[wJOKyKDBwMUOg{txO NYLsUIlzOjN2NEO4NFU>
SPAC1L NWLMbYtqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3nIT2lEPTB;Mz6wOkDDuSBzLkG0JO69VQ>? Mlv1NlM1PDN6MEW=
HUVEC MUTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3rWW|AuOjVizszN NHvWWmI4OiCq NX;lblZXTE2VTx?= MoXwbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MW[yN|IzQDBzNx?=
HMVEC MnG5R4VtdCCYaXHibYxqfHliQYPzZZk> MonHNE0zPSEQvF2= MYe3NkBp MWXEUXNQ MWrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NYPRbZhQOjN{MkiwNVc>
MHCC-97H MmrPR4VtdCCYaXHibYxqfHliQYPzZZk> Mn;INE0zPSEQvF2= MVS3NkBp MYLEUXNQ M4HiUYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MoOxNlMzOjhyMUe=
SMMC7721 NIfINVRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVnOT5ZyOC1{NTFOwG0> NEXxfJY4OiCq NVrxVXRkTE2VTx?= M4HBTIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MWqyN|IzQDBzNx?=
Huh-7 M4DzVGFxd3C2b4Ppd{BCe3OjeR?= NX;zeYN5OC1zMj61JO69VQ>? MXqyOEBp M330W2ROW00EoB?= NXLS[Wpve2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? MXOyNlI{ODR5OR?=
Sk-Hep1 MVLBdI9xfG:|aYOgRZN{[Xl? NGXrZ3gxNTF{LkWg{txO MYmyOEBp MomySG1UV8Li M{PudJNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NGTL[5UzOjJ|MES3PS=>
Hep3B MX;BdI9xfG:|aYOgRZN{[Xl? NU\OSXE{OC1zMj61JO69VQ>? NXfBToVLOjRiaB?= NU\YRYNCTE2VT9Mg MkTwd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> Mn\lNlIzOzB2N{m=
PLC5 MUjBdI9xfG:|aYOgRZN{[Xl? M2TyUFAuOTJwNTFOwG0> M2fDW|I1KGh? M1n1cWROW00EoB?= MUnz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NF3pcJAzOjJ|MES3PS=>
PLC5 MkTMR4VtdCCYaXHibYxqfHliQYPzZZk> M3O4e|AuOTVizszN MlTGO|IhcA>? MWjy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? M1GwV|IzOThyM{C4
Hep3B MVPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MV2wMVE2KM7:TR?= NYK5NJNmPzJiaB?= MX7y[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MYCyNlE5ODNyOB?=
Sk-Hep1 MnPIR4VtdCCYaXHibYxqfHliQYPzZZk> NVnHRVRUOC1zNTFOwG0> MmXVO|IhcA>? MoXRdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NVr2XXAyOjJzOECzNFg>
Huh-7 NYG3b3dMS2WubDDWbYFjcWyrdImgRZN{[Xl? NVzrblJ[OC1zNTFOwG0> NGfPOpY4OiCq M4W5XpJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NG\sbWQzOjF6MEOwPC=>
PLC5 NFr4[YlCeG:ydH;zbZMhSXO|YYm= M4H1VFAuOTVizszN MWKyOEBp NXLpcmFscW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NWjHcmtwOjJzOECzNFg>
Hep3B MYrBdI9xfG:|aYOgRZN{[Xl? MX2wMVE2KM7:TR?= MmSxNlQhcA>? MoXubY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NYG1RVRHOjJzOECzNFg>
Sk-Hep1 MnK3RZBweHSxc3nzJGF{e2G7 MYiwMVE2KM7:TR?= NH3rOngzPCCq MVTpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? MXWyNlE5ODNyOB?=
Huh-7 NIn4VHdCeG:ydH;zbZMhSXO|YYm= NXHVUZBkOC1zNTFOwG0> NWK5NpFMOjRiaB?= M{LNN4lv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MoTDNlIyQDB|MEi=
PLC5 M365bWZ2dmO2aX;uJGF{e2G7 NHvRNncxNTFyIN88US=> MVKyOEBp NX\QSWp7[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w M134NFIzOThyM{C4
Hep3B Mk\QSpVv[3Srb36gRZN{[Xl? MkjtNE0yOCEQvF2= MUOyOEBp NFrCbIJk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NGXyd2czOjF6MEOwPC=>
Sk-Hep1 NEX5XGJHfW6ldHnvckBCe3OjeR?= NVn6d4I{OC1zMDFOwG0> M{PjXlI1KGh? MmnRZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v NH7yTVAzOjF6MEOwPC=>
Huh-7 M33aTGZ2dmO2aX;uJGF{e2G7 MUiwMVExKM7:TR?= M375T|I1KGh? NUnKeZg5[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w MUmyNlE5ODNyOB?=
SW780 M2HrbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFf4PIo2KGR? NInScFNKSzVyPUWwJI5O M1qyTFIyOTF7Nk[x
RT112 NIfi[41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XXe|Uh\A>? M4PjW2lEPTB;MUWgcm0> NHy5eG8zOTFzOU[2NS=>
RT4 M3jwNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonsOUBl M132RWlEPTB;NTDuUS=> NH3qW|AzOTFzOU[2NS=>
JMSU1 M1\D[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUnESlV6PSCm NXrxW2trUUN3ME21NEBvVQ>? NYL4cYhHOjFzMUm2OlE>
J82 NXLEdYhIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3LWOFUh\A>? M4PjZWlEPTB;MUSwNEBvVQ>? M17rdVIyOTF7Nk[x
97-7 NEPXXFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkPPOUBl NX\VVINEUUN3ME2xNFAxKG6P NIC2bZIzOTFzOU[2NS=>
RT112 MkGwSpVv[3Srb36gRZN{[Xl? M{jzWVUxOCCwTR?= NXfoZnUyOjRiaB?= MXHpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? M3nkTVIyOTF7Nk[x
RT4 MnO3SpVv[3Srb36gRZN{[Xl? NXzlPGRGPTByIH7N NUT4RWtXOjRiaB?= NEDkWGFqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= Mkj4NlEyOTl4NkG=
MGH-U3 NIq5UopHfW6ldHnvckBCe3OjeR?= NGrKUVI2ODBibl2= M4OwTFI1KGh? NHzofXpqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= NVrWZ3p6OjFzMUm2OlE>
SW780 MlP4SpVv[3Srb36gRZN{[Xl? M2TwN|UxOCCwTR?= M4LxdVI1KGh? MXPpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NFPlZVkzOTFzOU[2NS=>
97-7 Mor3SpVv[3Srb36gRZN{[Xl? NWXybmN1PTByIH7N M{PMRlI1KGh? NFjGTYRqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= M3H5PFIyOTF7Nk[x
 J807C MXPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NWjOVo9KOC12MECgcm0> MXO0PEBp M{n5UYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NUDOXIlzOTV3OUi4NVQ>
Y373C M2LMRWNmdGxiVnnhZoltcXS7IFHzd4F6 NEjGbVkxNTRyMDDuUS=> NYPxSY5NPDhiaB?= NFzNNHdqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NGLmUlIyPTV7OEixOC=>
K650E MVPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4TrRVAuPDByIH7N M3XTTFQ5KGh? NVzhcm5zcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MmXDNVU2QTh6MUS=
G384D NIfB[25E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NV7iXYNFOC12MECgcm0> NWXFOpBZPDhiaB?= NF6yTHNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M4D6TFE2PTl6OEG0
F384L NV;aUZIzS2WubDDWbYFjcWyrdImgRZN{[Xl? M1vYc|AuPDByIH7N Mlr0OFghcA>? Ml75bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MXixOVU6QDhzNB?=
KMS11 NGDQO3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvve45UPzJiaB?= NIq4OGtKSzVyPUmwJI5O NGriRYEyPTV7OEixOC=>
KMS18 NVTDNll[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYW3NkBp MXvJR|UxRTV3MDDuUS=> NH70WoYyPTV7OEixOC=>
OPM2 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\DRVczKGh? MWnJR|UxRTlyIH7N M4jjNlE2PTl6OEG0
H929 Moj1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\hO|IhcA>? MmjQTWM2OD5iMkWwNEBvVQ>? MXOxOVU6QDhzNB?=
8226 NUiwbZZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjxVpo4OiCq M2e3ZmlEPTB-IEK1NFAhdk1? M3iwPFE2PTl6OEG0
U266 NG\qfWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWe3NkBp MkPITWM2OD5iMkWwNEBvVQ>? MUGxOVU6QDhzNB?=

... 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.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID