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.

Size Price Stock Quantity  
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

Choose Selective FLT3 Inhibitors

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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 M2Xvb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnSyTWM2OD1yLkS0PUDPxE1? MnfVNlUzODJyN{O=
SupB15-R NUTyWGQ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MofCTWM2OD1yLkW1PEDPxE1? MXiyOVIxOjB5Mx?=
BaF3-pSRα MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVK2N2NVUUN3ME2wMlY3QCEQvF2= Mom3NlUzODJyN{O=
BaF3-p210Bcr-Abl NEXRTmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1nBcWlEPTB;MD62PVIh|ryP M2WxTlI2OjB{MEez
BaF3-p210Bcr-Abl-T315I M{jhWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3jlR2lEPTB;Mj62NlYh|ryP MYiyOVIxOjB5Mx?=
CCRF-CEM MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVz6bJBSUUN3ME2wMlM6QCEQvF2= NX\yeFZpOjV{MEKwO|I>
CEM/C2 NVfTVG5VT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PtW2lEPTB;MT6xNlUh|ryP NITVeoozPTJyMkC3Ni=>
Nalm-6 NVjGUmdUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFqwcWFKSzVyPUCuN|gzKM7:TR?= NV7KV29HOjV{MEKwO|I>
SEM-K2 MlPTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmqwTWM2OD1yLkCyNkDPxE1? NVvMfXppOjV{MEKwO|I>
HB-1119 M3vTTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHvENIpKSzVyPUCuNFI5KM7:TR?= MWiyOVIxOjB5Mh?=
RS4:11 Ml62S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV3JR|UxRTJwOEGg{txO MkTtNlUzODJyN{K=
Nalm-6 M1zQSGFxd3C2b4Ppd{BCe3OjeR?= MU[yJO69VQ>? NYXJcHhtOjRxNEigbC=> NGLLV4hqdmS3Y3XzJIFxd3C2b4Ppd{Bz\XO3bITpcochcW5iYXLveZQhPzJnIH;mJINmdGxiZHXheIgh[W[2ZYKgNlQhcCC2cnXheI1mdnRiYX7kJFgyLSCjZoTldkA1QCCq NUfrfW1GOjV{MEKwO|I>
SEM-K2 NGHYOVhCeG:ydH;zbZMhSXO|YYm= NELiWY0xNjFxMTFOwG0> MWiyOEBp NUD6Z4dMcW6mdXPld{Bm[XKueTDhdI9xfG:|aYOgc4YhW0WPLVuyJINmdGy|IHH0JFAvOSEQvF2gZYZ1\XJiMkSgbC=> M1HRfFI2OjB{MEey
HCT-116 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXrJR|UxRTNwMEWwMlU5KM7:TR?= MVeyOFQ6PTd3MB?=
HT-29 NIGwNVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjLdW9KSzVyPUWuNlEvQTNizszN NFL2[ngzPDR7NUe1NC=>
SW-480 MljDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYW5[JRmUUN3ME20MlM{OC52NzFOwG0> NYnGfZpTOjR2OUW3OVA>
CaCO2 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWTONGpOUUN3ME2zMlI{OC54NDFOwG0> NHzsXowzPDR7NUe1NC=>
LS174T M2ToZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXnQdZl7UUN3ME20MlM{OC52NzFOwG0> MYKyOFQ6PTd3MB?=
HEC-1A NFz3SYFHfW6ldHnvckBCe3OjeR?= NI\yR5AxNjB3L{CuNU8xNjVizszN M{L5NFczKGh? MljOZ4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> NI\tN2QzPDR7NUe1NC=>
AN3CA NI\Hd|BHfW6ldHnvckBCe3OjeR?= M2X3ZVAvODVxMD6xM|AvPSEQvF2= NIj6RmE4OiCq M3;TWoNifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v NGe3OnozPDR7NUe1NC=>
MFE-296  NXzZbIhQTnWwY4Tpc44hSXO|YYm= NYSybnRNOC5yNT:wMlEwOC53IN88US=> MmTWO|IhcA>? NVThTplG[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? NUfYPHE6OjR2OUW3OVA>
UMC3 MmP1R4VtdCCYaXHibYxqfHliQYPzZZk> NX76OZdpOS1zMDFOwG0> MXK3NkBp NGDkfZhqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MVuyOFMzPTR4MR?=
5637 Mo\RR4VtdCCYaXHibYxqfHliQYPzZZk> MXOxMVExKM7:TR?= NEm5dZc4OiCq M2HabYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NEG5UmwzPDN{NUS2NS=>
HU456 M3rNTWNmdGxiVnnhZoltcXS7IFHzd4F6 M37JR|EuOTBizszN M2rp[FczKGh? MWrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M2Xo[VI1OzJ3NE[x
MGHU4 NFWySo1E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NGDDV2wyNTFyIN88US=> MkPYO|IhcA>? MUXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NWTlSGd1OjR|MkW0OlE>
HT1376 NYflPIVWS2WubDDWbYFjcWyrdImgRZN{[Xl? M1vWblEuOTBizszN M{T0bFczKGh? NVX2dHdLcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NGTjb|YzPDN{NUS2NS=>
RT112 M3rYRWNmdGxiVnnhZoltcXS7IFHzd4F6 M3TMTVEuOTBizszN MkDlO|IhcA>? NUW0[WhVcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MnfPNlQ{OjV2NkG=
T24 M4jse2NmdGxiVnnhZoltcXS7IFHzd4F6 MVixMVExKM7:TR?= Ml\WO|IhcA>? NF3nSZlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Ml3iNlQ{OjV2NkG=
BFTC905 NEHPbJRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MV:xMVExKM7:TR?= NGjkZ|k4OiCq NFG5WXRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NX2wfZlTOjR|MkW0OlE>
TCC-SUP NU\VWHpzS2WubDDWbYFjcWyrdImgRZN{[Xl? MV[xMVExKM7:TR?= NIXLWY44OiCq NFjCcnJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NEXVc|AzPDN{NUS2NS=>
RT4 NIq3VY5E\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1nZR|EuOTBizszN MonqO|IhcA>? MnH6bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NUfme3lFOjR|MkW0OlE>
HONE1 NUfsc4l4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2ruXlAvOS1zMDFOwG0> MlTrOFjDqGh? MX;pcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MnPxNlQzOzhyOUS=
HNE1 NFvCOG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYnLR3Z[OC5zLUGwJO69VQ>? NEnqN5Y1QMLiaB?= MWTpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= M4riUVI1OjN6MEm0
CNE2  NY\tbFh2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWqwMlEuOTBizszN NFzUSIE1QMLiaB?= NUDKUWZYcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M3nvVFI1OjN6MEm0
C666-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorENE4yNTFyIN88US=> M{T6dVQ5yqCq MXrpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= NXzWPIpQOjR{M{iwPVQ>
HeLa NVfudHh4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{PiXFAvOS1zMDFOwG0> Mon0NlQhcA>? NVjGfItScW6mdXPld{BIOi:PIHHydoV{fCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M3j1Z|I1OjN6MEm0
Hep3B NFXMTphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn;LNE4yNTFyIN88US=> MXSyOEBp MUXpcoR2[2W|IFeyxsBienKnc4VCpC=> M1nkVFI1OjN6MEm0
HepG2 M3rEOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWDxdYNIPDhiaB?= MVjJR|UxRTJwN{K3JOKyKDBwNEK5JO69VQ>? NU\NUYN7OjN3NE[1PVE>
Hep3B NEf0[4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojMOFghcA>? NVT3S2lXUUN3ME20MlIzOyEEsTCwMlg{QSEQvF2= MWSyN|U1PjV7MR?=
PLC/PRF5 NGHGbHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPnO|c1QCCq MkP0TWM2OD1zNj6xNlAhyrFiND6wNFEh|ryP M3TlflI{PTR4NUmx
Huh7 M3XKTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3K5R|Q5KGh? MXLJR|UxRTF3LkCwO{DDuSB5LkOzOEDPxE1? MlvUNlM2PDZ3OUG=
HepG2 M2rjSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MljhO|IhcA>? M1O3WmlEPTB;MT6yNFAhyrFiMD6yNlYh|ryP M3HGV|I{PTR4NUmx
Hep3B M1T3Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXrOdpA4PzJiaB?= M{HLXmlEPTB;MD64PVIhyrFiMD6wOFQh|ryP MYiyN|U1PjV7MR?=
PLC/PRF5 Mn\JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mny5O|IhcA>? Mnj0TWM2OD1|LkGxNEDDuSByLkOzO{DPxE1? M3:2eVI{PTR4NUmx
Huh7 NWjRV3ZET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnuO|IhcA>? M1PrOWlEPTB;Mz65PFAhyrFiMD64NFMh|ryP NWHUdY5WOjN3NE[1PVE>
MFE280 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXvJR|UxRTBwNEKgxtEhOC5yNjFOwG0> M1nKelI{PDR|OEC1
AN3CA NUPZOmtbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3r1UmlEPTB;MD61NEDDuSByLkGwJO69VQ>? NFfZXHozOzR2M{iwOS=>
HEC155 Ml\YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHNXmFsUUN3ME2wMlY3KMLzIECuNFkh|ryP MlHhNlM1PDN6MEW=
MFE296 NUGwdIFYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEe0[4JKSzVyPUCuOlYhyrFiMD6xPUDPxE1? MmnzNlM1PDN6MEW=
SPAC1S MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4O0fGlEPTB;MD63O{DDuSByLkC4JO69VQ>? MXOyN|Q1OzhyNR?=
RL952 NXzvbYhHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1jqSmlEPTB;MD65N{DDuSByLkCxJO69VQ>? NHPKUWMzOzR2M{iwOS=>
EN1 MkHmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3f5dWlEPTB;MT6wNkDDuSByLkK1JO69VQ>? MV:yN|Q1OzhyNR?=
SNGII NWG2[ZZOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYHJR|UxRTFwMkSgxtEhOC5{ODFOwG0> NHfqR|EzOzR2M{iwOS=>
ISHIKAWA MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVvJR|UxRTFwM{CgxtEhOC5zMTFOwG0> MWGyN|Q1OzhyNR?=
HEC1A MnLuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYDsUW1PUUN3ME2xMlM1KMLzIECuN|Ah|ryP NU\sdpRWOjN2NEO4NFU>
KLE NHzKSXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3PSVGlEPTB;MT6zO{DDuSByLkCyJO69VQ>? M3jLXlI{PDR|OEC1
SNGM NHzsSmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXzvPVhUUUN3ME2xMlQzKMLzIECuNVMh|ryP NWftNlFtOjN2NEO4NFU>
USPC2 NHvCb25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV3pNo1IUUN3ME2xMlYzKMLzIECuNFEh|ryP NFPRWmozOzR2M{iwOS=>
EN NHiyW5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYLJR|UxRTFwNk[gxtEhOC5yMTFOwG0> MkDqNlM1PDN6MEW=
MFE319 M3jydGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2HvVWlEPTB;MT64O{DDuSByLkS1JO69VQ>? MXSyN|Q1OzhyNR?=
EFE184 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF\IdVdKSzVyPUKuNFQhyrFiMD6xN{DPxE1? M3HRfVI{PDR|OEC1
ECC1 NEjhSJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTJwMEegxtEhOC5yMTFOwG0> MlHHNlM1PDN6MEW=
HEC1B MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnLoTWM2OD1{LkW3JOKyKDBwMkOg{txO MWmyN|Q1OzhyNR?=
USPC1 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3O1cmlEPTB;Mj62NEDDuSByLkGzJO69VQ>? MW[yN|Q1OzhyNR?=
SPAC1L NUfBWnJvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWOwZndtUUN3ME2zMlA3KMLzIEGuNVQh|ryP NFj2fY8zOzR2M{iwOS=>
HUVEC NWTnVXlnS2WubDDWbYFjcWyrdImgRZN{[Xl? M{KwU|AuOjVizszN MXW3NkBp NU\OPZpNTE2VTx?= MVnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M{PTTFI{OjJ6MEG3
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Huh-7 M4HoNGFxd3C2b4Ppd{BCe3OjeR?= NHjDdo4xNTF{LkWg{txO MXWyOEBp NYO0c28xTE2VT9Mg MVPz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NVTpVYViOjJ{M{C0O|k>
Sk-Hep1 NVvBfVM{SXCxcITvd4l{KEG|c3H5 MVGwMVEzNjVizszN MorZNlQhcA>? MnjhSG1UV8Li M2O3N5NmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> M1XnO|IzOjNyNEe5
Hep3B NX7S[FJnSXCxcITvd4l{KEG|c3H5 MYSwMVEzNjVizszN MYWyOEBp NIrUcYVFVVORwrC= MmDjd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> MlLwNlIzOzB2N{m=
PLC5 M{nZSGFxd3C2b4Ppd{BCe3OjeR?= Mnz5NE0yOi53IN88US=> MV:yOEBp NGLScmVFVVORwrC= M4e2bpNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NWjRTmI4OjJ{M{C0O|k>
PLC5 Ml\NR4VtdCCYaXHibYxqfHliQYPzZZk> NY\MTHZQOC1zNTFOwG0> NULicGNWPzJiaB?= MUPy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MonmNlIyQDB|MEi=
Hep3B NVjER|lxS2WubDDWbYFjcWyrdImgRZN{[Xl? M4njOFAuOTVizszN M33PSlczKGh? NUHXfFNEemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg NIHRUHgzOjF6MEOwPC=>
Sk-Hep1 MV\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NX33PJJwOC1zNTFOwG0> NEDYU|c4OiCq M3HKTJJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NUXsZZF[OjJzOECzNFg>
Huh-7 NHW4XFZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MoLXNE0yPSEQvF2= M1r1bFczKGh? MlzPdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NHfrR3YzOjF6MEOwPC=>
PLC5 MoS3RZBweHSxc3nzJGF{e2G7 M{O4[lAuOTVizszN MYCyOEBp NIrzWFBqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NGDMNYEzOjF6MEOwPC=>
Hep3B NWPxdXhQSXCxcITvd4l{KEG|c3H5 M1\UflAuOTVizszN M362NVI1KGh? M1\mNolv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M4\2T|IzOThyM{C4
Sk-Hep1 MoD4RZBweHSxc3nzJGF{e2G7 MV:wMVE2KM7:TR?= NGfQbWwzPCCq M{e1N4lv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NVL5RnQ2OjJzOECzNFg>
Huh-7 M176XmFxd3C2b4Ppd{BCe3OjeR?= NVjRNYJ{OC1zNTFOwG0> Ml\nNlQhcA>? MlrIbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MWSyNlE5ODNyOB?=
PLC5 M{X3Z2Z2dmO2aX;uJGF{e2G7 NHXFe|kxNTFyIN88US=> Mk\rNlQhcA>? NX7xcHV4[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w MWCyNlE5ODNyOB?=
Hep3B MlPkSpVv[3Srb36gRZN{[Xl? NX\KRWZPOC1zMDFOwG0> NFvyOGszPCCq NULiRpBY[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NV[yWodEOjJzOECzNFg>
Sk-Hep1 NFfGdG1HfW6ldHnvckBCe3OjeR?= Mn;mNE0yOCEQvF2= MlnoNlQhcA>? MULjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> MXqyNlE5ODNyOB?=
Huh-7 NVHNWWdVTnWwY4Tpc44hSXO|YYm= NFTUcYcxNTFyIN88US=> M1\jOlI1KGh? NH;SUHVk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NGLu[WwzOjF6MEOwPC=>
SW780 M2e2bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWfURXFPPSCm NUjDRVZpUUN3ME21NEBvVQ>? M1Lqd|IyOTF7Nk[x
RT112 MkTHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfvUJE2KGR? MX3JR|UxRTF3IH7N M2f0VVIyOTF7Nk[x
RT4 M3e3SGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlnZOUBl NEDsOo1KSzVyPUWgcm0> MoXKNlEyOTl4NkG=
JMSU1 NYHlZoFvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUm1JIQ> M{e0WWlEPTB;NUCgcm0> M3iyflIyOTF7Nk[x
J82 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2e2UVUh\A>? NH\ZZYFKSzVyPUG0NFAhdk1? MYiyNVEyQTZ4MR?=
97-7 NYTqW|M{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NELSNWc2KGR? M1Hw[mlEPTB;MUCwNEBvVQ>? M4W4NlIyOTF7Nk[x
RT112 M2fqU2Z2dmO2aX;uJGF{e2G7 NXnDfIRbPTByIH7N NFnveXEzPCCq MknYbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NEDmfpIzOTFzOU[2NS=>
RT4 NXfUUmpuTnWwY4Tpc44hSXO|YYm= MU[1NFAhdk1? NH;YOYUzPCCq NUnURpRRcW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz MVqyNVEyQTZ4MR?=
MGH-U3 NWKyZYJvTnWwY4Tpc44hSXO|YYm= NIDMSXk2ODBibl2= M1rYflI1KGh? M3rKXYlv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MoT6NlEyOTl4NkG=
SW780 NX\NOZByTnWwY4Tpc44hSXO|YYm= M3n4NFUxOCCwTR?= MV2yOEBp M4HDbolv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= NILqZlMzOTFzOU[2NS=>
97-7 M4HFTWZ2dmO2aX;uJGF{e2G7 NHTlT4Q2ODBibl2= M2PoVFI1KGh? MUfpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NGn1S44zOTFzOU[2NS=>
 J807C NGH1ZWhE\WyuIG\pZYJqdGm2eTDBd5NigQ>? Mn3yNE01ODBibl2= NFnnXFM1QCCq NGHpPGJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MYWxOVU6QDhzNB?=
Y373C MmfzR4VtdCCYaXHibYxqfHliQYPzZZk> NIjWXpoxNTRyMDDuUS=> MmPDOFghcA>? MmLrbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NVXNUmtWOTV3OUi4NVQ>
K650E MUjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NH\KWXQxNTRyMDDuUS=> M3r5d|Q5KGh? M3XSVolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NWjHNFlUOTV3OUi4NVQ>
G384D NFnzcGlE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MkK2NE01ODBibl2= NWLododyPDhiaB?= M1\JdIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MlrTNVU2QTh6MUS=
F384L NHzPZW5E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NETnS4kxNTRyMDDuUS=> M2T4fFQ5KGh? MlmxbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M4SydFE2PTl6OEG0
KMS11 Mo\mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWe0dlI5PzJiaB?= M4nMNGlEPTB;OUCgcm0> NWn6XGx{OTV3OUi4NVQ>
KMS18 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1:zRVczKGh? MojwTWM2OD13NUCgcm0> NFfBNHUyPTV7OEixOC=>
OPM2 M2Pvd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUG3NkBp MkLuTWM2OD17MDDuUS=> MlPaNVU2QTh6MUS=
H929 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWi3NkBp MYrJR|UxRiB{NUCwJI5O MljwNVU2QTh6MUS=
8226 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4rUUFczKGh? M2\TTGlEPTB-IEK1NFAhdk1? M{Kze|E2PTl6OEG0
U266 M{jMVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXv5SohbPzJiaB?= MV\JR|UxRiB{NUCwJI5O MYexOVU6QDhzNB?=

... 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 <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
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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID