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

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 M1jH[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfoU5JVUUN3ME2wMlQ1QSEQvF2= MXGyOVIxOjB5Mx?=
SupB15-R MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVWxS4FvUUN3ME2wMlU2QCEQvF2= NUHhbGRiOjV{MEKwO|M>
BaF3-pSRα NUnqR2lOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NInJSXFKSzVyPUCuOlY5KM7:TR?= MVqyOVIxOjB5Mx?=
BaF3-p210Bcr-Abl NInxVIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXnJR|UxRTBwNkmyJO69VQ>? MkfwNlUzODJyN{O=
BaF3-p210Bcr-Abl-T315I NIri[VFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTJwNkK2JO69VQ>? M4KwfFI2OjB{MEez
CCRF-CEM M3fUcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTBwM{m4JO69VQ>? MVeyOVIxOjB5Mh?=
CEM/C2 M3L1V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmfiTWM2OD1zLkGyOUDPxE1? M{TLTFI2OjB{MEey
Nalm-6 M4nQd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnkWHFKSzVyPUCuN|gzKM7:TR?= NWXJUo1DOjV{MEKwO|I>
SEM-K2 NYX0Nmk2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTjTXJKSzVyPUCuNFIzKM7:TR?= NULRNnpoOjV{MEKwO|I>
HB-1119 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEHrWlhKSzVyPUCuNFI5KM7:TR?= MYOyOVIxOjB5Mh?=
RS4:11 MlvCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjKfHNKSzVyPUKuPFEh|ryP NVuze5pNOjV{MEKwO|I>
Nalm-6 NGXtVoJCeG:ydH;zbZMhSXO|YYm= M4ThS|Ih|ryP MWWyOE81QCCq MX\pcoR2[2W|IHHwc5B1d3OrczDy[ZN2dHSrbnegbY4h[WKxdYSgO|ImKG:oIHPlcIwh\GWjdHigZYZ1\XJiMkSgbEB1emWjdH3lcpQh[W6mIEixKUBi\nSncjC0PEBp MmDTNlUzODJyN{K=
SEM-K2 MXjBdI9xfG:|aYOgRZN{[Xl? NVTFNYJSOC5zL{Gg{txO NWLCU|dKOjRiaB?= Mk[2bY5lfWOnczDlZZJtgSCjcH;weI9{cXNib3[gV2VONUt{IHPlcIx{KGG2IECuNUDPxE1iYX\0[ZIhOjRiaB?= M3PHdFI2OjB{MEey
HCT-116 MkDSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVXT[2p1UUN3ME2zMlA2OC53ODFOwG0> NVHhO|V6OjR2OUW3OVA>
HT-29 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTVwMkGuPVMh|ryP M3\NSlI1PDl3N{Ww
SW-480 MmDQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2r0T2lEPTB;ND6zN|AvPDdizszN M{LiTFI1PDl3N{Ww
CaCO2 MnLjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWG2OJR{UUN3ME2zMlI{OC54NDFOwG0> MYGyOFQ6PTd3MB?=
LS174T Mo\US5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHXIZ4xKSzVyPUSuN|MxNjR5IN88US=> NUDxNGE6OjR2OUW3OVA>
HEC-1A MmPqSpVv[3Srb36gRZN{[Xl? MW[wMlA2NzBwMT:wMlUh|ryP NHLud4o4OiCq NGLUc|dk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? MWKyOFQ6PTd3MB?=
AN3CA NXfsfHY4TnWwY4Tpc44hSXO|YYm= NEXmNlcxNjB3L{CuNU8xNjVizszN MWe3NkBp NWrIUVlp[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? MnThNlQ1QTV5NUC=
MFE-296  MX7GeY5kfGmxbjDBd5NigQ>? M2DVXlAvODVxMD6xM|AvPSEQvF2= MofrO|IhcA>? NG[4U3Vk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? NGjIfmYzPDR7NUe1NC=>
UMC3 MUTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NWPlS3g3OS1zMDFOwG0> MVK3NkBp M3z0PYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz Mn;XNlQ{OjV2NkG=
5637 Ml\zR4VtdCCYaXHibYxqfHliQYPzZZk> NITnOJMyNTFyIN88US=> NFW3S2M4OiCq M2DGbIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NIL1U5UzPDN{NUS2NS=>
HU456 MkTGR4VtdCCYaXHibYxqfHliQYPzZZk> NF3DUGoyNTFyIN88US=> NVPxc3dZPzJiaB?= M4XLOYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NEDoZ|AzPDN{NUS2NS=>
MGHU4 M4GyNWNmdGxiVnnhZoltcXS7IFHzd4F6 MoTpNU0yOCEQvF2= MlnQO|IhcA>? NWjmeFVtcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NWP6Z4p2OjR|MkW0OlE>
HT1376 M4jXdmNmdGxiVnnhZoltcXS7IFHzd4F6 M17Cb|EuOTBizszN MWm3NkBp Mn;xbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MkjXNlQ{OjV2NkG=
RT112 NYjvN2oxS2WubDDWbYFjcWyrdImgRZN{[Xl? NWKzWWkzOS1zMDFOwG0> NVfz[JFiPzJiaB?= NGDMc3RqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NV;lT2F5OjR|MkW0OlE>
T24 NX;IU4s4S2WubDDWbYFjcWyrdImgRZN{[Xl? NXjYWG97OS1zMDFOwG0> MVe3NkBp MV\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MVyyOFMzPTR4MR?=
BFTC905 MVjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4DkZ|EuOTBizszN NGnRV2I4OiCq M4TnNIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NEfu[W0zPDN{NUS2NS=>
TCC-SUP NU\xR5BkS2WubDDWbYFjcWyrdImgRZN{[Xl? NEj1cGcyNTFyIN88US=> MV:3NkBp MYnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MoTLNlQ{OjV2NkG=
RT4 MWrD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MWOxMVExKM7:TR?= NH;EenY4OiCq NVPlSFNrcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MoLXNlQ{OjV2NkG=
HONE1 NFz3RY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;5cm0xNjFvMUCg{txO NFj2XGw1QMLiaB?= NYnZWnpGcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NF;MSXczPDJ|OEC5OC=>
HNE1 MluxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWGwMlEuOTBizszN NYOwbYI3PDkEoHi= M1fLbolv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> M{XES|I1OjN6MEm0
CNE2  NV3KXVlpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoSyNE4yNTFyIN88US=> Mn34OFjDqGh? NHrDXXFqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MoPsNlQzOzhyOUS=
C666-1 Mnm4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrONE4yNTFyIN88US=> MWO0POKhcA>? M1zwVIlv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NFvJSnIzPDJ|OEC5OC=>
HeLa M{S4N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mm\zNE4yNTFyIN88US=> MVmyOEBp NWT1O3U{cW6mdXPld{BIOi:PIHHydoV{fCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MlXNNlQzOzhyOUS=
Hep3B Ml[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M13KeFAvOS1zMDFOwG0> NXLRdXptOjRiaB?= NUe4Z2FTcW6mdXPld{BIOsLiYYLy[ZN1yqB? MnLXNlQzOzhyOUS=
HepG2 NX\lS3FsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MljMOFghcA>? NEf5PIZKSzVyPUKuO|I4KMLzIECuOFI6KM7:TR?= M2GyXVI{PTR4NUmx
Hep3B MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmj0OFghcA>? NGXKT45KSzVyPUSuNlI{KMLzIECuPFM6KM7:TR?= NEDLV5MzOzV2NkW5NS=>
PLC/PRF5 MkXLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYm0PEBp NUnj[IRwUUN3ME2xOk4yOjBiwsGgOE4xODFizszN M1;sVVI{PTR4NUmx
Huh7 M1XUTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUGzXY97PDhiaB?= MX3JR|UxRTF3LkCwO{DDuSB5LkOzOEDPxE1? NFfWSpQzOzV2NkW5NS=>
HepG2 M4rJPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWm3NkBp NFLpRlVKSzVyPUGuNlAxKMLzIECuNlI3KM7:TR?= Mli1NlM2PDZ3OUG=
Hep3B NWHRToY6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFTwOGc4OiCq NEHYellKSzVyPUCuPFkzKMLzIECuNFQ1KM7:TR?= NETkb2czOzV2NkW5NS=>
PLC/PRF5 M1u5XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmj3O|IhcA>? NY[3WJJWUUN3ME2zMlEyOCEEsTCwMlM{PyEQvF2= MonuNlM2PDZ3OUG=
Huh7 MkPsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXvOR442PzJiaB?= NXywcGJTUUN3ME2zMlk5OCEEsTCwMlgxOyEQvF2= M4e5eVI{PTR4NUmx
MFE280 M4nvTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVTkdGJVUUN3ME2wMlQzKMLzIECuNFYh|ryP NEfRemQzOzR2M{iwOS=>
AN3CA NGPycWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\ON4ljUUN3ME2wMlUxKMLzIECuNVAh|ryP M2HtZ|I{PDR|OEC1
HEC155 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\TU404UUN3ME2wMlY3KMLzIECuNFkh|ryP NUDHOYNuOjN2NEO4NFU>
MFE296 NEDKdZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mki3TWM2OD1yLk[2JOKyKDBwMUmg{txO MVKyN|Q1OzhyNR?=
SPAC1S NXXPc3RwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXoN|lKSzVyPUCuO|chyrFiMD6wPEDPxE1? MVqyN|Q1OzhyNR?=
RL952 MorRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrmR21CUUN3ME2wMlk{KMLzIECuNFEh|ryP M2DUdFI{PDR|OEC1
EN1 Mn\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVrZXoNqUUN3ME2xMlAzKMLzIECuNlUh|ryP Mo\tNlM1PDN6MEW=
SNGII MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjVZow3UUN3ME2xMlI1KMLzIECuNlgh|ryP M3Kwe|I{PDR|OEC1
ISHIKAWA MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmr0TWM2OD1zLkOwJOKyKDBwMUGg{txO MXqyN|Q1OzhyNR?=
HEC1A MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MojBTWM2OD1zLkO0JOKyKDBwM{Cg{txO M4rkOlI{PDR|OEC1
KLE M2TOT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvrSoh[UUN3ME2xMlM4KMLzIECuNFIh|ryP MViyN|Q1OzhyNR?=
SNGM MmXzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlP5TWM2OD1zLkSyJOKyKDBwMUOg{txO MVWyN|Q1OzhyNR?=
USPC2 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlThTWM2OD1zLk[yJOKyKDBwMEGg{txO MViyN|Q1OzhyNR?=
EN MlvQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPLTWM2OD1zLk[2JOKyKDBwMEGg{txO NYrpS41kOjN2NEO4NFU>
MFE319 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\ZToFQUUN3ME2xMlg4KMLzIECuOFUh|ryP NVq2eWtYOjN2NEO4NFU>
EFE184 M1vHR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoX1TWM2OD1{LkC0JOKyKDBwMUOg{txO MkO1NlM1PDN6MEW=
ECC1 MmHFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrWV4h6UUN3ME2yMlA4KMLzIECuNFEh|ryP MmLaNlM1PDN6MEW=
HEC1B NUS2d|RGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1nVOmlEPTB;Mj61O{DDuSByLkKzJO69VQ>? M3LXV|I{PDR|OEC1
USPC1 MkW1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU\JR|UxRTJwNkCgxtEhOC5zMzFOwG0> NXvP[4pHOjN2NEO4NFU>
SPAC1L NH;hNJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLXTWM2OD1|LkC2JOKyKDFwMUSg{txO MWOyN|Q1OzhyNR?=
HUVEC MWjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NV3RU3B6OC1{NTFOwG0> NXnNRodJPzJiaB?= MVXEUXNQ NFHhU2pqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MmrFNlMzOjhyMUe=
HMVEC M2rtUGNmdGxiVnnhZoltcXS7IFHzd4F6 Mom3NE0zPSEQvF2= NV;RTHk3PzJiaB?= NHe5blRFVVOR Mn;EbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> Mle5NlMzOjhyMUe=
MHCC-97H NXPSSWxGS2WubDDWbYFjcWyrdImgRZN{[Xl? Mle3NE0zPSEQvF2= M1vHUFczKGh? NFvwSpFFVVOR MWLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M3XVclI{OjJ6MEG3
SMMC7721 NXfwfG5VS2WubDDWbYFjcWyrdImgRZN{[Xl? MYKwMVI2KM7:TR?= NGO5[pI4OiCq NIDuO3VFVVOR MV3pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NYLMeWE2OjN{MkiwNVc>
Huh-7 NXPFWHRYSXCxcITvd4l{KEG|c3H5 MWewMVEzNjVizszN NIPhdFEzPCCq MmGwSG1UV8Li NFj1VJJ{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz MUSyNlI{ODR5OR?=
Sk-Hep1 MYHBdI9xfG:|aYOgRZN{[Xl? NIHlfogxNTF{LkWg{txO M1:xRlI1KGh? MnvuSG1UV8Li MkPVd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NV7K[IFiOjJ{M{C0O|k>
Hep3B NXniWWVmSXCxcITvd4l{KEG|c3H5 NF;kT|MxNTF{LkWg{txO NFHWZoEzPCCq M{XH[GROW00EoB?= MYDz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NWXlPY1DOjJ{M{C0O|k>
PLC5 NHjUdlBCeG:ydH;zbZMhSXO|YYm= NHyyfmwxNTF{LkWg{txO NGHEVJYzPCCq MXHEUXNQyqB? M2T2WJNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> Moj2NlIzOzB2N{m=
PLC5 NXjGV5NWS2WubDDWbYFjcWyrdImgRZN{[Xl? NXroV4d7OC1zNTFOwG0> MVe3NkBp NFu4OWFz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= Mo\UNlIyQDB|MEi=
Hep3B MVzD[YxtKF[rYXLpcIl1gSCDc4PhfS=> Mly1NE0yPSEQvF2= NYHDSYV7PzJiaB?= NIjHTolz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NGHEOHAzOjF6MEOwPC=>
Sk-Hep1 NFnYbVFE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NXj4Snh6OC1zNTFOwG0> M1X5XlczKGh? MVny[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? M2HrRVIzOThyM{C4
Huh-7 M4X6cGNmdGxiVnnhZoltcXS7IFHzd4F6 NX7wOYFlOC1zNTFOwG0> MYm3NkBp NWHJ[Jh2emWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg NGPNR2gzOjF6MEOwPC=>
PLC5 MofDRZBweHSxc3nzJGF{e2G7 MXmwMVE2KM7:TR?= NVnIcW53OjRiaB?= NYPYd3dpcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NXzwO|FtOjJzOECzNFg>
Hep3B NVzKWWNXSXCxcITvd4l{KEG|c3H5 MUKwMVE2KM7:TR?= MUWyOEBp NIDTT2xqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NFO0VGUzOjF6MEOwPC=>
Sk-Hep1 M2nDXmFxd3C2b4Ppd{BCe3OjeR?= Mo\ZNE0yPSEQvF2= M1LCWVI1KGh? NEHFNlRqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MWeyNlE5ODNyOB?=
Huh-7 MofaRZBweHSxc3nzJGF{e2G7 NIiyVGUxNTF3IN88US=> M2HCd|I1KGh? MY\pcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? NXfmNnZFOjJzOECzNFg>
PLC5 NFO2T3FHfW6ldHnvckBCe3OjeR?= M3nKWlAuOTBizszN NIrMR4ozPCCq MnzkZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v NIC3So0zOjF6MEOwPC=>
Hep3B MlOxSpVv[3Srb36gRZN{[Xl? MYWwMVExKM7:TR?= Ml;JNlQhcA>? NXPjVnBX[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NV;vRppjOjJzOECzNFg>
Sk-Hep1 MlHwSpVv[3Srb36gRZN{[Xl? NWLwXHFQOC1zMDFOwG0> MVGyOEBp MorhZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v MVuyNlE5ODNyOB?=
Huh-7 MYrGeY5kfGmxbjDBd5NigQ>? M{LOTVAuOTBizszN MnLCNlQhcA>? M{nLboNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? MYqyNlE5ODNyOB?=
SW780 NXHvdnpQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIe0XFI2KGR? MkHKTWM2OD13MDDuUS=> M1jmRVIyOTF7Nk[x
RT112 MnPXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzEPHdSPSCm NVTR[Ho2UUN3ME2xOUBvVQ>? NYTYSVNNOjFzMUm2OlE>
RT4 NYDZUXhlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXG1JIQ> NH;ENG5KSzVyPUWgcm0> MViyNVEyQTZ4MR?=
JMSU1 NYXETFBQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkDlOUBl Mn71TWM2OD13MDDuUS=> Mn3DNlEyOTl4NkG=
J82 MkfOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXq1JIQ> MoH5TWM2OD1zNECwJI5O MWOyNVEyQTZ4MR?=
97-7 NF[2e5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fpWFUh\A>? M1n2OmlEPTB;MUCwNEBvVQ>? MVOyNVEyQTZ4MR?=
RT112 M1POU2Z2dmO2aX;uJGF{e2G7 Mk[3OVAxKG6P Mk\LNlQhcA>? MU\pcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? Moq5NlEyOTl4NkG=
RT4 MV\GeY5kfGmxbjDBd5NigQ>? NUfpRVhGPTByIH7N NF7RPI0zPCCq M122bolv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MlewNlEyOTl4NkG=
MGH-U3 MWPGeY5kfGmxbjDBd5NigQ>? NFO4WHc2ODBibl2= M13HOVI1KGh? M3qzS4lv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= NIG1V|czOTFzOU[2NS=>
SW780 NGO1R5RHfW6ldHnvckBCe3OjeR?= MXy1NFAhdk1? MnexNlQhcA>? M1HKd4lv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MVSyNVEyQTZ4MR?=
97-7 MV;GeY5kfGmxbjDBd5NigQ>? MYe1NFAhdk1? NGPKbIIzPCCq MXjpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? MnThNlEyOTl4NkG=
 J807C MVzD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MnjZNE01ODBibl2= Mn\MOFghcA>? MYDpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NF\WSVAyPTV7OEixOC=>
Y373C M1TSZWNmdGxiVnnhZoltcXS7IFHzd4F6 NE[3NosxNTRyMDDuUS=> MoLQOFghcA>? MUXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M1v3WFE2PTl6OEG0
K650E MlfxR4VtdCCYaXHibYxqfHliQYPzZZk> MVmwMVQxOCCwTR?= M{XPNFQ5KGh? MYHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NH3WeWoyPTV7OEixOC=>
G384D M2nkT2NmdGxiVnnhZoltcXS7IFHzd4F6 MmfoNE01ODBibl2= Mn7JOFghcA>? NXnLXnpwcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MYexOVU6QDhzNB?=
F384L M2jKOGNmdGxiVnnhZoltcXS7IFHzd4F6 MkfFNE01ODBibl2= NED0bmI1QCCq MmftbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NFTOSpYyPTV7OEixOC=>
KMS11 NVzHSm9QT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYG3NkBp NGrO[3ZKSzVyPUmwJI5O Mn7ONVU2QTh6MUS=
KMS18 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoOxO|IhcA>? MWPJR|UxRTV3MDDuUS=> M2mycVE2PTl6OEG0
OPM2 NVnnfnFkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1jhXlczKGh? NEG5UY1KSzVyPUmwJI5O MXuxOVU6QDhzNB?=
H929 Mm\lS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVyyV|RkPzJiaB?= NG\DcppKSzVyPjCyOVAxKG6P M4fCc|E2PTl6OEG0
8226 Mlj3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWC3NkBp MkC1TWM2OD5iMkWwNEBvVQ>? MkH2NVU2QTh6MUS=
U266 NEH2[G5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXK3NkBp MWfJR|UxRiB{NUCwJI5O Mn;FNVU2QTh6MUS=

... 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]
+ 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 <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

Tech Support

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID