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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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 NXu4TmI3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MorDTWM2OD1yLkS0PUDPxE1? NYq2WXlxOjV{MEKwO|M>
SupB15-R MnLmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3W3NWlEPTB;MD61OVgh|ryP NE\ZUmgzPTJyMkC3Ny=>
BaF3-pSRα NWm4bG44T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIPhO4RKSzVyPUCuOlY5KM7:TR?= MluyNlUzODJyN{O=
BaF3-p210Bcr-Abl NUnHXYVrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYTofXlmUUN3ME2wMlY6OiEQvF2= M{LpXVI2OjB{MEez
BaF3-p210Bcr-Abl-T315I NV;LU4FFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnGbnI3UUN3ME2yMlYzPiEQvF2= MY[yOVIxOjB5Mx?=
CCRF-CEM NWPRV3JkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfOe4JKSzVyPUCuN|k5KM7:TR?= MYWyOVIxOjB5Mh?=
CEM/C2 NG\TT5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH\1WmlKSzVyPUGuNVI2KM7:TR?= NXHITWF4OjV{MEKwO|I>
Nalm-6 NUDYU4lsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH35cXpKSzVyPUCuN|gzKM7:TR?= NWrCN49kOjV{MEKwO|I>
SEM-K2 MoruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2f2SmlEPTB;MD6wNlIh|ryP NGD4TmYzPTJyMkC3Ni=>
HB-1119 NVrpSZM4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmP1TWM2OD1yLkCyPEDPxE1? MUKyOVIxOjB5Mh?=
RS4:11 M1HSR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGjCe3pKSzVyPUKuPFEh|ryP MnntNlUzODJyN{K=
Nalm-6 NFnubm1CeG:ydH;zbZMhSXO|YYm= M3XWSVIh|ryP NHjrR|IzPC92ODDo MX3pcoR2[2W|IHHwc5B1d3OrczDy[ZN2dHSrbnegbY4h[WKxdYSgO|ImKG:oIHPlcIwh\GWjdHigZYZ1\XJiMkSgbEB1emWjdH3lcpQh[W6mIEixKUBi\nSncjC0PEBp MYqyOVIxOjB5Mh?=
SEM-K2 MYDBdI9xfG:|aYOgRZN{[Xl? M37TS|AvOS9zIN88US=> MXOyOEBp M2jOTYlv\HWlZYOg[YFzdHliYYDvdJRwe2m|IH;mJHNGVS2NMjDj[YxteyCjdDCwMlEh|ryPIHHmeIVzKDJ2IHi= M17tOlI2OjB{MEey
HCT-116 NVnOfIc6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHLtcXNKSzVyPUOuNFUxNjV6IN88US=> MXKyOFQ6PTd3MB?=
HT-29 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml\UTWM2OD13LkKxMlk{KM7:TR?= NEXaNGMzPDR7NUe1NC=>
SW-480 M4r2PGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTRwM{OwMlQ4KM7:TR?= M3nZflI1PDl3N{Ww
CaCO2 MontS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1i4UWlEPTB;Mz6yN|AvPjRizszN NWLnTVNPOjR2OUW3OVA>
LS174T NHraPVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmOyTWM2OD12LkOzNE41PyEQvF2= NFf2O4UzPDR7NUe1NC=>
HEC-1A NHH3Z5hHfW6ldHnvckBCe3OjeR?= Mn\mNE4xPS9yLkGvNE42KM7:TR?= MVG3NkBp NXXOcnl{[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? MV:yOFQ6PTd3MB?=
AN3CA NWi0SWg6TnWwY4Tpc44hSXO|YYm= NHr2N4YxNjB3L{CuNU8xNjVizszN M4K4UlczKGh? M13ESYNifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v NEHqS4szPDR7NUe1NC=>
MFE-296  M3[3SGZ2dmO2aX;uJGF{e2G7 MUewMlA2NzBwMT:wMlUh|ryP NYDIOIk{PzJiaB?= NEfrTFNk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? NGjwdHQzPDR7NUe1NC=>
UMC3 MVnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3X5OFEuOTBizszN M3q2SFczKGh? M1jvNolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MWSyOFMzPTR4MR?=
5637 NH:3SotE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MoiyNU0yOCEQvF2= M{Tqb|czKGh? NVr0bIc1cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mn\ONlQ{OjV2NkG=
HU456 NWDZVnJCS2WubDDWbYFjcWyrdImgRZN{[Xl? NUK5bWMzOS1zMDFOwG0> NXnwTJI6PzJiaB?= NWjSZ41VcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mnr0NlQ{OjV2NkG=
MGHU4 NHfsPWtE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M2nkZ|EuOTBizszN MY[3NkBp MWXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M1m5NlI1OzJ3NE[x
HT1376 NHfLfoRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MWOxMVExKM7:TR?= NFnFWYQ4OiCq M3jmPIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M{fSO|I1OzJ3NE[x
RT112 NXWzTIN7S2WubDDWbYFjcWyrdImgRZN{[Xl? Ml:wNU0yOCEQvF2= NH:zV5k4OiCq MmjzbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M3TJO|I1OzJ3NE[x
T24 M2roTmNmdGxiVnnhZoltcXS7IFHzd4F6 MmnVNU0yOCEQvF2= MnniO|IhcA>? NGCzUXdqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MmHhNlQ{OjV2NkG=
BFTC905 NGfqcIdE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M3P0XFEuOTBizszN NH:zfpM4OiCq M4K1folvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NIDPO5YzPDN{NUS2NS=>
TCC-SUP MmLCR4VtdCCYaXHibYxqfHliQYPzZZk> Mk[3NU0yOCEQvF2= M4nSU|czKGh? NGrPeFVqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MnW0NlQ{OjV2NkG=
RT4 NX7VdHJYS2WubDDWbYFjcWyrdImgRZN{[Xl? NIi5cnYyNTFyIN88US=> NEPke5E4OiCq M3TpVYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MWiyOFMzPTR4MR?=
HONE1 MnTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zpPFAvOS1zMDFOwG0> NXu2cIxXPDkEoHi= M1XC[4lv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MkXhNlQzOzhyOUS=
HNE1 NWi4VG1TT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrjTYZYOC5zLUGwJO69VQ>? MVe0POKhcA>? M3XBfIlv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NUfNWIpTOjR{M{iwPVQ>
CNE2  MnXQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEez[20xNjFvMUCg{txO MkK3OFjDqGh? NWnOVWE1cW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NY[y[Fg4OjR{M{iwPVQ>
C666-1 NUDhWJFnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYiwMlEuOTBizszN NHjX[mw1QMLiaB?= NX7kfVE{cW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M4m4c|I1OjN6MEm0
HeLa Mn3QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnvtNE4yNTFyIN88US=> MmGxNlQhcA>? NHfJeGZqdmS3Y3XzJGczN01iYYLy[ZN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz Mmr5NlQzOzhyOUS=
Hep3B MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3jSol5OC5zLUGwJO69VQ>? MXiyOEBp M4jMNolv\HWlZYOgS|LDqGG{cnXzeOKh Mn32NlQzOzhyOUS=
HepG2 M3PaXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHHqbG01QCCq NIf0V3lKSzVyPUKuO|I4KMLzIECuOFI6KM7:TR?= NIC2PXQzOzV2NkW5NS=>
Hep3B M{XtOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkfEOFghcA>? MVrJR|UxRTRwMkKzJOKyKDBwOEO5JO69VQ>? NI\PSZgzOzV2NkW5NS=>
PLC/PRF5 M4DCW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4TLVFQ5KGh? NGntO21KSzVyPUG2MlEzOCEEsTC0MlAxOSEQvF2= MkDzNlM2PDZ3OUG=
Huh7 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrGeVQ1QCCq MlT2TWM2OD1zNT6wNFchyrFiNz6zN|Qh|ryP NYjzRVF[OjN3NE[1PVE>
HepG2 NVnhcmpFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfUO|IhcA>? NHPURopKSzVyPUGuNlAxKMLzIECuNlI3KM7:TR?= NFnKV2gzOzV2NkW5NS=>
Hep3B MnO4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUm3NkBp M3nv[WlEPTB;MD64PVIhyrFiMD6wOFQh|ryP NX;kPWFwOjN3NE[1PVE>
PLC/PRF5 NVTqOJRXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mkm5O|IhcA>? NVLrV3l6UUN3ME2zMlEyOCEEsTCwMlM{PyEQvF2= M1m0ZVI{PTR4NUmx
Huh7 NYDwTWFGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlroO|IhcA>? M1XmPGlEPTB;Mz65PFAhyrFiMD64NFMh|ryP NVXwdmsxOjN3NE[1PVE>
MFE280 NVvZbFJ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWXJR|UxRTBwNEKgxtEhOC5yNjFOwG0> NYnj[G5DOjN2NEO4NFU>
AN3CA NEjBS5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2LqVGlEPTB;MD61NEDDuSByLkGwJO69VQ>? M2r6dlI{PDR|OEC1
HEC155 MmG2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmO5TWM2OD1yLk[2JOKyKDBwMEmg{txO NH\xUZkzOzR2M{iwOS=>
MFE296 NXOxN|h5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVK1[lNYUUN3ME2wMlY3KMLzIECuNVkh|ryP M4TieVI{PDR|OEC1
SPAC1S M1f0Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlqzTWM2OD1yLke3JOKyKDBwMEig{txO MkfONlM1PDN6MEW=
RL952 NG\oVlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFzhSFRKSzVyPUCuPVMhyrFiMD6wNUDPxE1? NVfxeZRXOjN2NEO4NFU>
EN1 NUTWdIppT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoTrTWM2OD1zLkCyJOKyKDBwMkWg{txO NX;hSI9UOjN2NEO4NFU>
SNGII NXzG[VZsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHW1UFdKSzVyPUGuNlQhyrFiMD6yPEDPxE1? NHvndpEzOzR2M{iwOS=>
ISHIKAWA NV71TFNUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTFwM{CgxtEhOC5zMTFOwG0> M2fqXVI{PDR|OEC1
HEC1A MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{DCVmlEPTB;MT6zOEDDuSByLkOwJO69VQ>? MWWyN|Q1OzhyNR?=
KLE NXrVNlRiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTFwM{egxtEhOC5yMjFOwG0> NGLhe4czOzR2M{iwOS=>
SNGM NG\DZVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXBTWM2OD1zLkSyJOKyKDBwMUOg{txO M37DfFI{PDR|OEC1
USPC2 Mkn4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\jZ3JSUUN3ME2xMlYzKMLzIECuNFEh|ryP MnjKNlM1PDN6MEW=
EN MmDFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLOco1KSzVyPUGuOlYhyrFiMD6wNUDPxE1? M{D4fFI{PDR|OEC1
MFE319 NF\1OmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTFwOEegxtEhOC52NTFOwG0> M1L3OFI{PDR|OEC1
EFE184 MmjTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX7JR|UxRTJwMESgxtEhOC5zMzFOwG0> NHntRXgzOzR2M{iwOS=>
ECC1 MkTHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7ZSW9KSzVyPUKuNFchyrFiMD6wNUDPxE1? NHPGTlUzOzR2M{iwOS=>
HEC1B NHvEUVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn;DTWM2OD1{LkW3JOKyKDBwMkOg{txO NHPvPJEzOzR2M{iwOS=>
USPC1 NV3MWJl3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUjJR|UxRTJwNkCgxtEhOC5zMzFOwG0> Ml\ENlM1PDN6MEW=
SPAC1L M3OzfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoXTTWM2OD1|LkC2JOKyKDFwMUSg{txO MWmyN|Q1OzhyNR?=
HUVEC MV7D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NULrXYJHOC1{NTFOwG0> NWj6VYVqPzJiaB?= NEDy[GxFVVOR NV3ONHVTcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NUXU[ohTOjN{MkiwNVc>
HMVEC MV;D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NUTTVpVqOC1{NTFOwG0> MkfOO|IhcA>? NUjMOXpNTE2VTx?= MnTibY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MWOyN|IzQDBzNx?=
MHCC-97H MYPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MWqwMVI2KM7:TR?= NILBWVM4OiCq M4\zOmROW09? NG[5RWpqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M4XxbFI{OjJ6MEG3
SMMC7721 NH3vS4FE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NGrmV20xNTJ3IN88US=> NFT2W444OiCq NVm1THpnTE2VTx?= NFrJfYNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MoXWNlMzOjhyMUe=
Huh-7 M1rEVmFxd3C2b4Ppd{BCe3OjeR?= MW[wMVEzNjVizszN MoLCNlQhcA>? MoXzSG1UV8Li NXTuT5pUe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? MYGyNlI{ODR5OR?=
Sk-Hep1 NVTsfGgxSXCxcITvd4l{KEG|c3H5 NHPRdJkxNTF{LkWg{txO MkjsNlQhcA>? MmXNSG1UV8Li MmXFd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NILVPZgzOjJ|MES3PS=>
Hep3B NFXW[3lCeG:ydH;zbZMhSXO|YYm= NGLLSVIxNTF{LkWg{txO MX6yOEBp MWnEUXNQyqB? MXfz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NX\TTmtROjJ{M{C0O|k>
PLC5 M322ZWFxd3C2b4Ppd{BCe3OjeR?= M2S5ZVAuOTJwNTFOwG0> Mn;BNlQhcA>? MkCzSG1UV8Li NEHWOIp{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz NVLOU|RROjJ{M{C0O|k>
PLC5 MX3D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MYiwMVE2KM7:TR?= NFniXVU4OiCq NFH3Xmhz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= M2rYNFIzOThyM{C4
Hep3B MWTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1TLbFAuOTVizszN MmPhO|IhcA>? MULy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NGHSeGwzOjF6MEOwPC=>
Sk-Hep1 NEDDXHRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NEP3PW0xNTF3IN88US=> MlXHO|IhcA>? Mn3pdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M1zXcVIzOThyM{C4
Huh-7 NVvxOHlWS2WubDDWbYFjcWyrdImgRZN{[Xl? NVS3UoIxOC1zNTFOwG0> NVruTJBFPzJiaB?= MVny[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NXXlVGxLOjJzOECzNFg>
PLC5 MX;BdI9xfG:|aYOgRZN{[Xl? MVWwMVE2KM7:TR?= MUGyOEBp M4DrS4lv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MkfLNlIyQDB|MEi=
Hep3B NYDQb3ZTSXCxcITvd4l{KEG|c3H5 NYDiU29EOC1zNTFOwG0> MUiyOEBp M1jCOIlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M1LIeFIzOThyM{C4
Sk-Hep1 MUPBdI9xfG:|aYOgRZN{[Xl? NI[zflExNTF3IN88US=> NUDF[XoyOjRiaB?= MYXpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? MUmyNlE5ODNyOB?=
Huh-7 NVvUWYdoSXCxcITvd4l{KEG|c3H5 NHL6bWYxNTF3IN88US=> MWiyOEBp NFPQWlNqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MmixNlIyQDB|MEi=
PLC5 MVzGeY5kfGmxbjDBd5NigQ>? MYKwMVExKM7:TR?= NWjoTppSOjRiaB?= MYPjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> M363flIzOThyM{C4
Hep3B MVjGeY5kfGmxbjDBd5NigQ>? M13wXFAuOTBizszN NH3mfGgzPCCq NYHjU4p[[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w MmrHNlIyQDB|MEi=
Sk-Hep1 MnfxSpVv[3Srb36gRZN{[Xl? MU[wMVExKM7:TR?= MXqyOEBp MYrjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> MnjkNlIyQDB|MEi=
Huh-7 MmTpSpVv[3Srb36gRZN{[Xl? MkC1NE0yOCEQvF2= MnzONlQhcA>? NFvjWXBk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? M{GxNlIzOThyM{C4
SW780 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWHWeHQ{PSCm NXvIVY5[UUN3ME21NEBvVQ>? MmjjNlEyOTl4NkG=
RT112 MnjYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmLiOUBl MmPrTWM2OD1zNTDuUS=> M2jsXlIyOTF7Nk[x
RT4 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLwOUBl NFnienRKSzVyPUWgcm0> M3G1PFIyOTF7Nk[x
JMSU1 NV3Y[Y05T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYK1JIQ> NXrYblY3UUN3ME21NEBvVQ>? Mm\QNlEyOTl4NkG=
J82 NXfNRo5lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjySI42KGR? NVPpWo9tUUN3ME2xOFAxKG6P MmLvNlEyOTl4NkG=
97-7 Mof6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1H4bFUh\A>? Mnj0TWM2OD1zMECwJI5O M4nZO|IyOTF7Nk[x
RT112 Mlv2SpVv[3Srb36gRZN{[Xl? MlPkOVAxKG6P Mn;rNlQhcA>? MkTybY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NXn2bJZkOjFzMUm2OlE>
RT4 Mk[ySpVv[3Srb36gRZN{[Xl? NHe4TWU2ODBibl2= MmX3NlQhcA>? NHPDbHRqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MV[yNVEyQTZ4MR?=
MGH-U3 NV24eYVmTnWwY4Tpc44hSXO|YYm= NW\scGRYPTByIH7N MlXxNlQhcA>? M3fuS4lv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MWGyNVEyQTZ4MR?=
SW780 Ml3jSpVv[3Srb36gRZN{[Xl? NFL3NIs2ODBibl2= NXTtbW91OjRiaB?= M4i2[olv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MWmyNVEyQTZ4MR?=
97-7 MkjpSpVv[3Srb36gRZN{[Xl? MWS1NFAhdk1? MnPvNlQhcA>? MoK3bY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| MofqNlEyOTl4NkG=
 J807C M1fPWWNmdGxiVnnhZoltcXS7IFHzd4F6 M3LxWlAuPDByIH7N NHjWXYo1QCCq Mo\HbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MomyNVU2QTh6MUS=
Y373C NUCyUHBuS2WubDDWbYFjcWyrdImgRZN{[Xl? MoHzNE01ODBibl2= NV64VoJOPDhiaB?= NGT6eJRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NVvIdY9XOTV3OUi4NVQ>
K650E MVrD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NF\B[WExNTRyMDDuUS=> MVW0PEBp NVz6dXpMcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NGX2UW8yPTV7OEixOC=>
G384D NEP2fYFE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NUOxV5dxOC12MECgcm0> NWfsWo06PDhiaB?= MXLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NHvicYsyPTV7OEixOC=>
F384L NI\WUWFE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MYmwMVQxOCCwTR?= NHLOOGk1QCCq NX\DfoZxcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MoXZNVU2QTh6MUS=
KMS11 M1jaTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1y2UlczKGh? NIPK[2RKSzVyPUmwJI5O MU[xOVU6QDhzNB?=
KMS18 M4H6Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkO0O|IhcA>? MWLJR|UxRTV3MDDuUS=> NX;CVo0yOTV3OUi4NVQ>
OPM2 NE[4emlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXTib3VZPzJiaB?= M2LST2lEPTB;OUCgcm0> MXyxOVU6QDhzNB?=
H929 NHzzW21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\VUHc5PzJiaB?= M3ziPWlEPTB-IEK1NFAhdk1? M4Tr[|E2PTl6OEG0
8226 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3rLdlczKGh? M2rESWlEPTB-IEK1NFAhdk1? MWCxOVU6QDhzNB?=
U266 M2LnOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUi3NkBp MVXJR|UxRiB{NUCwJI5O NUjGXY1QOTV3OUi4NVQ>

... 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
in solvent
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

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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