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 NXvOO5FmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17BWmlEPTB;MD60OFkh|ryP NGjZOpkzPTJyMkC3Ny=>
SupB15-R M33tWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnexTWM2OD1yLkW1PEDPxE1? M17lfFI2OjB{MEez
BaF3-pSRα NXvCcZpGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV\hW4ltUUN3ME2wMlY3QCEQvF2= MVmyOVIxOjB5Mx?=
BaF3-p210Bcr-Abl NHHDNYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmDmTWM2OD1yLk[5NkDPxE1? MlXDNlUzODJyN{O=
BaF3-p210Bcr-Abl-T315I M1\zR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYLJR|UxRTJwNkK2JO69VQ>? MX2yOVIxOjB5Mx?=
CCRF-CEM MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;qdGlEPTB;MD6zPVgh|ryP NFjnNoUzPTJyMkC3Ni=>
CEM/C2 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\FeZdKSzVyPUGuNVI2KM7:TR?= MVqyOVIxOjB5Mh?=
Nalm-6 M{HCU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTBwM{iyJO69VQ>? M1fIUlI2OjB{MEey
SEM-K2 M4LreWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3PENWlEPTB;MD6wNlIh|ryP NGDKdoozPTJyMkC3Ni=>
HB-1119 MnnlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXnZV2JXUUN3ME2wMlAzQCEQvF2= MXmyOVIxOjB5Mh?=
RS4:11 NIjWSZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWLvfZc5UUN3ME2yMlgyKM7:TR?= NYryVFIyOjV{MEKwO|I>
Nalm-6 M2[0SmFxd3C2b4Ppd{BCe3OjeR?= NEH1UlIzKM7:TR?= MX[yOE81QCCq NFi0cmJqdmS3Y3XzJIFxd3C2b4Ppd{Bz\XO3bITpcochcW5iYXLveZQhPzJnIH;mJINmdGxiZHXheIgh[W[2ZYKgNlQhcCC2cnXheI1mdnRiYX7kJFgyLSCjZoTldkA1QCCq MmDpNlUzODJyN{K=
SEM-K2 M2HCRmFxd3C2b4Ppd{BCe3OjeR?= Mo\6NE4yNzFizszN MmWwNlQhcA>? NUf6N3lOcW6mdXPld{Bm[XKueTDhdI9xfG:|aYOgc4YhW0WPLVuyJINmdGy|IHH0JFAvOSEQvF2gZYZ1\XJiMkSgbC=> MkjQNlUzODJyN{K=
HCT-116 M3rpcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFqyUXRKSzVyPUOuNFUxNjV6IN88US=> NVG1NnFwOjR2OUW3OVA>
HT-29 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmTPTWM2OD13LkKxMlk{KM7:TR?= NWfSPZY1OjR2OUW3OVA>
SW-480 MnzGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVrSb|NnUUN3ME20MlM{OC52NzFOwG0> NXLUNFZFOjR2OUW3OVA>
CaCO2 M1\rTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{C2WGlEPTB;Mz6yN|AvPjRizszN M4TQO|I1PDl3N{Ww
LS174T MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\JWI4{UUN3ME20MlM{OC52NzFOwG0> MYiyOFQ6PTd3MB?=
HEC-1A MXzGeY5kfGmxbjDBd5NigQ>? MlzjNE4xPS9yLkGvNE42KM7:TR?= NWjyO296PzJiaB?= NIrzXIpk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? Ml7CNlQ1QTV5NUC=
AN3CA NVTwT2xqTnWwY4Tpc44hSXO|YYm= M1frb|AvODVxMD6xM|AvPSEQvF2= MYq3NkBp NVnsOYVC[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? NXP4PWxPOjR2OUW3OVA>
MFE-296  NYjHRndxTnWwY4Tpc44hSXO|YYm= MUSwMlA2NzBwMT:wMlUh|ryP NWLUWVk5PzJiaB?= NGi4ZlZk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? MUSyOFQ6PTd3MB?=
UMC3 NVfke2p4S2WubDDWbYFjcWyrdImgRZN{[Xl? M4qzOVEuOTBizszN NHzLOXk4OiCq MlrGbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NXrEZ5FqOjR|MkW0OlE>
5637 MV7D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NFHYR3AyNTFyIN88US=> NGLQOnM4OiCq MmXubY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NEDJcFUzPDN{NUS2NS=>
HU456 MmCzR4VtdCCYaXHibYxqfHliQYPzZZk> MUOxMVExKM7:TR?= NH7hbVg4OiCq M1P1W4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NGrHUYUzPDN{NUS2NS=>
MGHU4 MWjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MnG1NU0yOCEQvF2= MV:3NkBp M2fwRYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NUjBem5xOjR|MkW0OlE>
HT1376 NIDQdpdE\WyuIG\pZYJqdGm2eTDBd5NigQ>? Mn3PNU0yOCEQvF2= NGfpUI84OiCq MoDLbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NWW1V3dTOjR|MkW0OlE>
RT112 NV:5c2VbS2WubDDWbYFjcWyrdImgRZN{[Xl? NFPjcIUyNTFyIN88US=> MnXSO|IhcA>? NInkS4tqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MWCyOFMzPTR4MR?=
T24 M1PTVGNmdGxiVnnhZoltcXS7IFHzd4F6 Mm\hNU0yOCEQvF2= MnfxO|IhcA>? NIi1XG9qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NIr3RWIzPDN{NUS2NS=>
BFTC905 MUPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MYWxMVExKM7:TR?= MW[3NkBp M4XhZYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MYOyOFMzPTR4MR?=
TCC-SUP NGLZOFhE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M3TTVVEuOTBizszN NXLGcWRjPzJiaB?= NYfJRpR2cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MnLhNlQ{OjV2NkG=
RT4 NHf3SIVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NYPEcJNUOS1zMDFOwG0> NUn1WlllPzJiaB?= MVXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NUG5Zpg6OjR|MkW0OlE>
HONE1 M2DG[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M324OFAvOS1zMDFOwG0> MXS0POKhcA>? NF\sNJVqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> M3vjOlI1OjN6MEm0
HNE1 M{DodGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{fRcVAvOS1zMDFOwG0> M2fKSVQ5yqCq NX7XdY9bcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M3;lV|I1OjN6MEm0
CNE2  NFjES5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrZS5lDOC5zLUGwJO69VQ>? M{fwVFQ5yqCq NULndpYycW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz Ml73NlQzOzhyOUS=
C666-1 MmLwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHnYfpExNjFvMUCg{txO NVrBcYFYPDkEoHi= MVTpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MVKyOFI{QDB7NB?=
HeLa NV63NZZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrDbYIyOC5zLUGwJO69VQ>? NFyyZlUzPCCq Mn7ibY5lfWOnczDHNk9OKGG{cnXzeEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> M1Lac|I1OjN6MEm0
Hep3B NHTVdZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MljJNE4yNTFyIN88US=> MWCyOEBp MkfTbY5lfWOnczDHNuKh[XK{ZYP0xsA> NX73W2FROjR{M{iwPVQ>
HepG2 M4ezO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVXYVI5XPDhiaB?= NF\qToFKSzVyPUKuO|I4KMLzIECuOFI6KM7:TR?= MmjqNlM2PDZ3OUG=
Hep3B M3rxVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV60PEBp MWTJR|UxRTRwMkKzJOKyKDBwOEO5JO69VQ>? NXvFOYlsOjN3NE[1PVE>
PLC/PRF5 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXSzWZdIPDhiaB?= NIHUR4FKSzVyPUG2MlEzOCEEsTC0MlAxOSEQvF2= NHTqVlUzOzV2NkW5NS=>
Huh7 NWeyTmo2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NG\3WFQ1QCCq MmjKTWM2OD1zNT6wNFchyrFiNz6zN|Qh|ryP NYXVNIdsOjN3NE[1PVE>
HepG2 MlnKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUKxZldHPzJiaB?= MXzJR|UxRTFwMkCwJOKyKDBwMkK2JO69VQ>? MmC4NlM2PDZ3OUG=
Hep3B NV:0[ZE2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPiW5k4OiCq MnK4TWM2OD1yLki5NkDDuSByLkC0OEDPxE1? MmPBNlM2PDZ3OUG=
PLC/PRF5 NVvFS5RrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGHuTo44OiCq MV;JR|UxRTNwMUGwJOKyKDBwM{O3JO69VQ>? MoPFNlM2PDZ3OUG=
Huh7 M3\lbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLDO|IhcA>? MnTFTWM2OD1|Lkm4NEDDuSByLkiwN{DPxE1? NXvFcppGOjN3NE[1PVE>
MFE280 MnHVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NID0cVhKSzVyPUCuOFIhyrFiMD6wOkDPxE1? MXqyN|Q1OzhyNR?=
AN3CA MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlHQTWM2OD1yLkWwJOKyKDBwMUCg{txO NV3G[pVOOjN2NEO4NFU>
HEC155 NX3xOoRxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFWwUHJKSzVyPUCuOlYhyrFiMD6wPUDPxE1? NHL5U4IzOzR2M{iwOS=>
MFE296 Mne1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3v2[GlEPTB;MD62OkDDuSByLkG5JO69VQ>? NFX1SWEzOzR2M{iwOS=>
SPAC1S MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M37xPWlEPTB;MD63O{DDuSByLkC4JO69VQ>? NX;tdpVoOjN2NEO4NFU>
RL952 MlTHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIWwbW1KSzVyPUCuPVMhyrFiMD6wNUDPxE1? MV2yN|Q1OzhyNR?=
EN1 NUm1[HJuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXjwPHhoUUN3ME2xMlAzKMLzIECuNlUh|ryP NXezOGRCOjN2NEO4NFU>
SNGII NVfxSoxCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvzTWM2OD1zLkK0JOKyKDBwMkig{txO NF;lXJMzOzR2M{iwOS=>
ISHIKAWA M2XlVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmfUTWM2OD1zLkOwJOKyKDBwMUGg{txO M1vDcFI{PDR|OEC1
HEC1A NV7XWpprT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXjXd4UxUUN3ME2xMlM1KMLzIECuN|Ah|ryP M{HFUVI{PDR|OEC1
KLE NHq1fIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTFwM{egxtEhOC5yMjFOwG0> NXTs[ZhJOjN2NEO4NFU>
SNGM M{jVTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHe4ZpRKSzVyPUGuOFIhyrFiMD6xN{DPxE1? MnKzNlM1PDN6MEW=
USPC2 M1zzfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXZfVFKSzVyPUGuOlIhyrFiMD6wNUDPxE1? M4LCcFI{PDR|OEC1
EN NWXaVYl1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{jX[GlEPTB;MT62OkDDuSByLkCxJO69VQ>? MXOyN|Q1OzhyNR?=
MFE319 MkPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfyR29JUUN3ME2xMlg4KMLzIECuOFUh|ryP Mmi3NlM1PDN6MEW=
EFE184 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHMTWM2OD1{LkC0JOKyKDBwMUOg{txO MnOxNlM1PDN6MEW=
ECC1 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTUTWM2OD1{LkC3JOKyKDBwMEGg{txO NGrjd3AzOzR2M{iwOS=>
HEC1B M{\oemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\jTWM2OD1{LkW3JOKyKDBwMkOg{txO MYmyN|Q1OzhyNR?=
USPC1 M{PNXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFHheW9KSzVyPUKuOlAhyrFiMD6xN{DPxE1? NWXaOYRZOjN2NEO4NFU>
SPAC1L NV\HPXJNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDQfW5KSzVyPUOuNFYhyrFiMT6xOEDPxE1? Mmn3NlM1PDN6MEW=
HUVEC NG\MSoRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M2TMNFAuOjVizszN M3LpPVczKGh? Mn:1SG1UVw>? M37HTIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MYKyN|IzQDBzNx?=
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Sk-Hep1 M3zTW2Fxd3C2b4Ppd{BCe3OjeR?= MkDmNE0yOi53IN88US=> NVTjXWlQOjRiaB?= NFLVOnlFVVORwrC= MWrz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M1\ZdFIzOjNyNEe5
Hep3B MUXBdI9xfG:|aYOgRZN{[Xl? MoTVNE0yOi53IN88US=> M171NVI1KGh? M13xfmROW00EoB?= NWnH[mxLe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? MVqyNlI{ODR5OR?=
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PLC5 NX;XdlJYS2WubDDWbYFjcWyrdImgRZN{[Xl? NV;TeZVvOC1zNTFOwG0> NWTYVFUyPzJiaB?= NF\xOWlz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NHzyTYczOjF6MEOwPC=>
Hep3B NEDUeGhE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M{O5d|AuOTVizszN M2HRUlczKGh? NHm5OXZz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MYKyNlE5ODNyOB?=
Sk-Hep1 MnrTR4VtdCCYaXHibYxqfHliQYPzZZk> NEjveZkxNTF3IN88US=> MXW3NkBp MkPXdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi Mn;nNlIyQDB|MEi=
Huh-7 M2DXRmNmdGxiVnnhZoltcXS7IFHzd4F6 NIXhTXgxNTF3IN88US=> NFe1c2k4OiCq NFnWeY9z\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NHzwRXQzOjF6MEOwPC=>
PLC5 NXvCO4t{SXCxcITvd4l{KEG|c3H5 M3rCelAuOTVizszN MlTMNlQhcA>? MoTmbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NYrhTnRUOjJzOECzNFg>
Hep3B M{\ubGFxd3C2b4Ppd{BCe3OjeR?= NWTCbZFtOC1zNTFOwG0> NWLQVnR6OjRiaB?= MlHYbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? Mlr3NlIyQDB|MEi=
Sk-Hep1 Mo[3RZBweHSxc3nzJGF{e2G7 MkfVNE0yPSEQvF2= MV[yOEBp M1fSSIlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NEDmZXMzOjF6MEOwPC=>
Huh-7 MX3BdI9xfG:|aYOgRZN{[Xl? MYmwMVE2KM7:TR?= M1nKWlI1KGh? M2rSNYlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NVz3cllPOjJzOECzNFg>
PLC5 M4LvN2Z2dmO2aX;uJGF{e2G7 NUPKXVRWOC1zMDFOwG0> MlzWNlQhcA>? NHu1bmRk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? M1rsW|IzOThyM{C4
Hep3B NFPySVFHfW6ldHnvckBCe3OjeR?= MmrPNE0yOCEQvF2= NWrlZlZ1OjRiaB?= Ml;vZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v Mn:wNlIyQDB|MEi=
Sk-Hep1 MUPGeY5kfGmxbjDBd5NigQ>? MWCwMVExKM7:TR?= NEeybFkzPCCq NGrjWYNk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NVH2dG1QOjJzOECzNFg>
Huh-7 NX7ue4p[TnWwY4Tpc44hSXO|YYm= NEj2bnUxNTFyIN88US=> NHnWd5AzPCCq M17BWYNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? NUnUVZJJOjJzOECzNFg>
SW780 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlzpOUBl NFvOdZFKSzVyPUWwJI5O NFPPbokzOTFzOU[2NS=>
RT112 NX;MWpdjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkT0OUBl M4i4V2lEPTB;MUWgcm0> NV3qOIY5OjFzMUm2OlE>
RT4 M{DrNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXnNW82KGR? NHKxeG1KSzVyPUWgcm0> NX2ySpFCOjFzMUm2OlE>
JMSU1 NHq1S4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY\HS5M6PSCm MlnRTWM2OD13MDDuUS=> NYPnNFhYOjFzMUm2OlE>
J82 NUTSZ3J{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW[1JIQ> NHjscFdKSzVyPUG0NFAhdk1? M3XPTFIyOTF7Nk[x
97-7 M1f1Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVzFV2dCPSCm M{PyOmlEPTB;MUCwNEBvVQ>? M4DrUVIyOTF7Nk[x
RT112 MXPGeY5kfGmxbjDBd5NigQ>? M{S2dlUxOCCwTR?= NHLjfIMzPCCq NF7J[2dqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= M{\FVFIyOTF7Nk[x
RT4 NUTnXY14TnWwY4Tpc44hSXO|YYm= MXW1NFAhdk1? NE\sb2QzPCCq MXnpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? MnX5NlEyOTl4NkG=
MGH-U3 MnzuSpVv[3Srb36gRZN{[Xl? NF7WUW42ODBibl2= NWjFeFlsOjRiaB?= M{fQVYlv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= NXTYUFN[OjFzMUm2OlE>
SW780 NFK4WXFHfW6ldHnvckBCe3OjeR?= NXzxSGtIPTByIH7N MWGyOEBp MYTpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NGj5ZXEzOTFzOU[2NS=>
97-7 NFLV[Y5HfW6ldHnvckBCe3OjeR?= M{jOTlUxOCCwTR?= NWPFeGVzOjRiaB?= M{HsR4lv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= M3HneFIyOTF7Nk[x
 J807C NVniS3IxS2WubDDWbYFjcWyrdImgRZN{[Xl? M4PE[FAuPDByIH7N MYS0PEBp MXzpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MXOxOVU6QDhzNB?=
Y373C NYjWN4hlS2WubDDWbYFjcWyrdImgRZN{[Xl? NFLJSJUxNTRyMDDuUS=> NV64ZoM5PDhiaB?= MVHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NXf0R5NLOTV3OUi4NVQ>
K650E MmnCR4VtdCCYaXHibYxqfHliQYPzZZk> NHm1NYMxNTRyMDDuUS=> NHzmO5U1QCCq NW\XRXZGcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NYL0NVhZOTV3OUi4NVQ>
G384D NV31[5FnS2WubDDWbYFjcWyrdImgRZN{[Xl? NXLzNItjOC12MECgcm0> M13ZbFQ5KGh? NE\ZSpNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NIi4fIwyPTV7OEixOC=>
F384L Mm\3R4VtdCCYaXHibYxqfHliQYPzZZk> M{\nU|AuPDByIH7N MXG0PEBp M2THZolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MYGxOVU6QDhzNB?=
KMS11 M4T2TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH3pdFE4OiCq NEXCO4RKSzVyPUmwJI5O MUSxOVU6QDhzNB?=
KMS18 NEPmVllIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLCfIszPzJiaB?= MmLsTWM2OD13NUCgcm0> MnnFNVU2QTh6MUS=
OPM2 M{LKZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXjlepp{PzJiaB?= M1f3cWlEPTB;OUCgcm0> NFmyc2UyPTV7OEixOC=>
H929 M1\R[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE\ER3Q4OiCq NXHrdYE1UUN3ME6gNlUxOCCwTR?= NWXoT2k1OTV3OUi4NVQ>
8226 NUDseW85T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnyxO|IhcA>? MYPJR|UxRiB{NUCwJI5O NXTXUFJ[OTV3OUi4NVQ>
U266 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWe3NkBp NH\zbZpKSzVyPjCyOVAxKG6P NGrOR|MyPTV7OEixOC=>

... 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(Data is from Selleck tests instead of citations):
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
NCT00831792 Completed Prostate Cancer M.D. Anderson Cancer Center|Novartis April 7 2010 Phase 2
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
NCT02116803 Completed Solid Tumors Novartis Pharmaceuticals|Novartis May 28 2014 Phase 2|Phase 3
NCT01262027 Active not recruiting Breast Cancer M.D. Anderson Cancer Center|Novartis January 27 2012 Phase 2
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

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