Dovitinib (TKI-258, CHIR-258)

Catalog No.S1018

Dovitinib (TKI-258, CHIR-258) Chemical Structure

Molecular Weight(MW): 392.43

Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.

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In DMSO USD 191 In stock
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7 Customer Reviews

  • In vitro assays on CUX1-FGFR1-expressing Ba/F3 cells. a. IL-3 deprivation of Ba/F3 cells transduced with CUX1-FGFR1 resulted in transformation to growth factor independent growth. The mean growth ±SEM of three separate measurements over four consecutive days is presented. b. The dose-response curves of CUX1-FGFR1-transduced Ba/F3 cells, treated with TKI258 and PKC412 for 48 hours in the absence or presence of IL-3 (2 ng/ml) are presented. Points represent the average results of two experiments done in triplicate plotted with the curve-fitting GraphPad Prism 5 software; bars, SD. The calculated IC50 for each inhibitor is indicated. c. Western blot analyses of CUX1-FGFR1-transformed Ba/F3 cells after treatment with PKC412 and TKI258. Phosphorylation of CUX1-FGFR1 and its downstream effectors STAT5 and RPS6K decreased with increasing inhibitor concentrations. Expression of total CUX1-FGFR1, STAT5 and RPS6K remained unaffected. d. Effect of PKC412 and TKI258 on apoptosis of CUX1-FGFR1-expressing Ba/F3 cells after treatment for 48 hours. The percentage of apoptotic plus necrotic CUX1-FGFR1-transduced Ba/F3 cells is indicated.

    haematologica 2011 96, 922-926. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

    RT112 cells were exposed to PD173074 (PD) (500 nM) for 0-24 h, TKI-258 (TK) (500 nM) or SU5402 (SU) (5 nM) for 1 h. Cells were lysed, FGFR3 was immunoprecipitated (immunoprecipitated, IP) and blots (immunoblot, IB) were probed for phospho-tyrosine and reprobed for FGFR3 or probed for phospho-ERK and reprobed for total ERK.

    Brit J Cancer 2010 104, 75-82. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Cells were exposed to PD173074 or TKI-258 (500 nM) for 24 h. Cell cycle profile was analysed using the Guava Easycyte Plus flow cytometry system.

    Brit J Cancer 2010 104, 75-82. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

     

    Orthotopic xenografts of HNSCC cell lines (A) SCC-1 and (B) OSC-19 were treated with dovitinib (20 mg/kg/day). In addition, the OSC-19 xenografts were treated with +/ radiation therapy. Marker, mean for triplicate; bars, SE. Statistical significance by unpaired t-test, p < 0.05.

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Treatments were initiated at time of orthotopic implantation. Growth stabilization was seen by day 8 of treatment (Fig. B). On day 17, tumors were har-vested and histological analysis was performed (Fig. C). Following Ki67 staining, tumors from control xenografts were found to have a higher percentage of proliferating cells (62%) compared to those treated with dovitinib (14%; p = 0.005). The incidence of lymph nodes metastasis was greater in the control cohort ( n = 15) com-pared to those treated with dovitinib (n = 5).

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

    Dose–response curves for HNSCC cells and fibroblasts treated in vitro with dovitinib (0–1000 nM). Boxes, mean for triplicate; bars, SE

    Oral Oncol 2012 48, 1242-9. Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

  • Ba/F3 cell lines expressing the recombinant TEL/kinase domain fusion protein for FGFR1-4 .Cells were grown in RPMI 1640 containing 10% FBS and 500 ng/mL puromycin. The parental Ba/F3 cell line transduced with an empty vector was grown in 10 ng/mL IL-3 (R & D systems). Cell viability was assessed at 72 hours using the Cell Titer 96 Aqueous One Solution (Promega). Data were plotted as percent viability relative to vehicle-treated cells and are shown as mean (±SD) from 3 experiments.

    AACR 2011 Dovitinib (TKI-258, CHIR-258) purchased from Selleck.

Purity & Quality Control

Choose Selective FLT3 Inhibitors

Biological Activity

Description Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.
Targets
FLT3 [1]
(Cell-free assay)
c-Kit [1]
(Cell-free assay)
FGFR1 [1]
(Cell-free assay)
VEGFR3/FLT4 [1]
(Cell-free assay)
FGFR3 [1]
(Cell-free assay)
1 nM 2 nM 8 nM 8 nM 9 nM
In vitro

Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 of 25 nM. In addition, Dovitinib inhibits proliferation of B9 cells expressing each of the various activated mutants of FGFR3. Interestingly, there are minimal observed differences in the sensitivity of the different FGFR3 mutations to Dovitinib, with the IC50 ranging from 70 to 90 nM for each of the various mutations. IL-6-dependent B9 cells containing vector only (B9-MINV cells are resistant to the inhibitory activity of Dovitinib at concentrations up to 1 μM. Dovitinib inhibits cell proliferation of KMS11 (FGFR3-Y373C), OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells with IC50 of 90 nM (KMS11 and OPM2) and 550 nM, respectively. Dovitinib inhibits FGF-mediated ERK1/2 phosphorylation and induces cytotoxicity in FGFR3-expressing primary MM cells. BMSCs does confer a modest degree of resistance with 44.6% growth inhibition for cells treated with 500 nM Dovitinib and cultured on stroma compared with 71.6% growth inhibition for cells grown without BMSCs. Dovitinib inhibits proliferation of M-NFS-60, an M-CSF growth-driven mouse myeloblastic cell line with a median effective concentration (EC50) of 220 nM. [1] Treatment of SK-HEP1 cells with Dovitinib results in a dose-dependent reduction in cell number and G2/M phase arrest with reduction in the G0/G1 and S phases, inhibition of anchorage-independent growth and blockage of bFGF-induced cell motility. The IC50 for Dovitinib in SK-HEP1 cells is approximately 1.7 μM. Dovitinib also significantly reduces the basal phosphorylation levels of FGFR-1, FGFR substrate 2α (FRS2-α) and ERK1/2 but not Akt in both SK-HEP1 and 21-0208 cells. In 21-0208 HCC cells, Dovitinib significantly inhibits bFGF-induced phosphorylation of FGFR-1, FRS2-α, ERK1/2 but not Akt. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SupB15 M2HiVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV7JR|UxRTBwNES5JO69VQ>? M3;WN|I2OjB{MEez
SupB15-R M3zTfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFrhepRKSzVyPUCuOVU5KM7:TR?= M1PPOVI2OjB{MEez
BaF3-pSRα M{TKT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXvJR|UxRTBwNk[4JO69VQ>? MXmyOVIxOjB5Mx?=
BaF3-p210Bcr-Abl MljlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVjJR|UxRTBwNkmyJO69VQ>? MXKyOVIxOjB5Mx?=
BaF3-p210Bcr-Abl-T315I M4L0emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXezTFJbUUN3ME2yMlYzPiEQvF2= NU\GUmZ4OjV{MEKwO|M>
CCRF-CEM M3HBc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;0VVdKSzVyPUCuN|k5KM7:TR?= MmrFNlUzODJyN{K=
CEM/C2 M2GxbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETzNFBKSzVyPUGuNVI2KM7:TR?= M1rSO|I2OjB{MEey
Nalm-6 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUW4eI5lUUN3ME2wMlM5OiEQvF2= M3Hh[FI2OjB{MEey
SEM-K2 NGPhUWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXiUlFnUUN3ME2wMlAzOiEQvF2= MVyyOVIxOjB5Mh?=
HB-1119 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTBwMEK4JO69VQ>? MluyNlUzODJyN{K=
RS4:11 NX;yPHM2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7POZBKSzVyPUKuPFEh|ryP NVuyfZFxOjV{MEKwO|I>
Nalm-6 MmfERZBweHSxc3nzJGF{e2G7 NIHzSXAzKM7:TR?= MoDGNlQwPDhiaB?= MUDpcoR2[2W|IHHwc5B1d3OrczDy[ZN2dHSrbnegbY4h[WKxdYSgO|ImKG:oIHPlcIwh\GWjdHigZYZ1\XJiMkSgbEB1emWjdH3lcpQh[W6mIEixKUBi\nSncjC0PEBp NFrSW|IzPTJyMkC3Ni=>
SEM-K2 NYXYWHdiSXCxcITvd4l{KEG|c3H5 MoXFNE4yNzFizszN NHrsOHgzPCCq MUHpcoR2[2W|IHXhdox6KGGyb4D0c5NqeyCxZjDTSW0uUzJiY3XscJMh[XRiMD6xJO69VSCjZoTldkAzPCCq M362Z|I2OjB{MEey
HCT-116 M3HSdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2X4U2lEPTB;Mz6wOVAvPThizszN M33kTlI1PDl3N{Ww
HT-29 M{fO[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUSyVpY5UUN3ME21MlIyNjl|IN88US=> NVHDdJNyOjR2OUW3OVA>
SW-480 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTnWFZ4UUN3ME20MlM{OC52NzFOwG0> MYqyOFQ6PTd3MB?=
CaCO2 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWrJR|UxRTNwMkOwMlY1KM7:TR?= M1f1N|I1PDl3N{Ww
LS174T NVX6XVh1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2nhSmlEPTB;ND6zN|AvPDdizszN M1HHTFI1PDl3N{Ww
HEC-1A NVfkclJ1TnWwY4Tpc44hSXO|YYm= M3fMZVAvODVxMD6xM|AvPSEQvF2= NH7HdHo4OiCq M{XM[4NifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v M17Ib|I1PDl3N{Ww
AN3CA MXzGeY5kfGmxbjDBd5NigQ>? M4[0U|AvODVxMD6xM|AvPSEQvF2= NXXqS|gyPzJiaB?= NH7rWGFk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? NGHYVWszPDR7NUe1NC=>
MFE-296  NHm4W3FHfW6ldHnvckBCe3OjeR?= NXHle4h6OC5yNT:wMlEwOC53IN88US=> MmDGO|IhcA>? MUnjZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> NF20[YgzPDR7NUe1NC=>
UMC3 M1e0ZWNmdGxiVnnhZoltcXS7IFHzd4F6 NIPHcI0yNTFyIN88US=> NWTiVWpqPzJiaB?= MYLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NEnKdJQzPDN{NUS2NS=>
5637 MlmyR4VtdCCYaXHibYxqfHliQYPzZZk> MXOxMVExKM7:TR?= MVi3NkBp MYXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M3TwTFI1OzJ3NE[x
HU456 Mk\iR4VtdCCYaXHibYxqfHliQYPzZZk> NUn5c3RWOS1zMDFOwG0> Mme4O|IhcA>? MnLRbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MlizNlQ{OjV2NkG=
MGHU4 MXLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M2\UTlEuOTBizszN MUK3NkBp NH\rSmxqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MlS0NlQ{OjV2NkG=
HT1376 MnfPR4VtdCCYaXHibYxqfHliQYPzZZk> NVnWdY9MOS1zMDFOwG0> MWm3NkBp NX3MSG4zcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MlXjNlQ{OjV2NkG=
RT112 MlPhR4VtdCCYaXHibYxqfHliQYPzZZk> NYHGeGdlOS1zMDFOwG0> MUG3NkBp MmHnbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M{\kZ|I1OzJ3NE[x
T24 Mlq0R4VtdCCYaXHibYxqfHliQYPzZZk> Ml31NU0yOCEQvF2= MkS5O|IhcA>? MW\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MWCyOFMzPTR4MR?=
BFTC905 MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MX2xMVExKM7:TR?= MmK4O|IhcA>? Mn\2bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NXnx[pl[OjR|MkW0OlE>
TCC-SUP MVjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NHPTRVkyNTFyIN88US=> MXu3NkBp NYT4fWI5cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mln6NlQ{OjV2NkG=
RT4 MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NFfFTlMyNTFyIN88US=> MVu3NkBp M1PNWYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NF3wXGozPDN{NUS2NS=>
HONE1 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7V[ZVlOC5zLUGwJO69VQ>? NXr6R2o6PDkEoHi= NF[xSZNqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NXHE[2dMOjR{M{iwPVQ>
HNE1 M4DwVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWCwMlEuOTBizszN M1viTFQ5yqCq MYTpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MVKyOFI{QDB7NB?=
CNE2  M3XsV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX7JZ2pqOC5zLUGwJO69VQ>? M2XLR|Q5yqCq Mk\pbY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy MUWyOFI{QDB7NB?=
C666-1 M1\YZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV[wMlEuOTBizszN NFjTNoY1QMLiaB?= Mkj5bY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy NIjBeG0zPDJ|OEC5OC=>
HeLa M4LGXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTZNE4yNTFyIN88US=> MkfSNlQhcA>? MnflbY5lfWOnczDHNk9OKGG{cnXzeEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MU[yOFI{QDB7NB?=
Hep3B NXPzN2p3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEPpeHYxNjFvMUCg{txO MUGyOEBp MW\pcoR2[2W|IFeyxsBienKnc4VCpC=> MX2yOFI{QDB7NB?=
HepG2 NVTRRm5YT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PCWVQ5KGh? M4rLNGlEPTB;Mj63NlchyrFiMD60Nlkh|ryP MWGyN|U1PjV7MR?=
Hep3B MkToS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjTSoM1QCCq MVzJR|UxRTRwMkKzJOKyKDBwOEO5JO69VQ>? MUKyN|U1PjV7MR?=
PLC/PRF5 NF3vUo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnnNI41QCCq M3nNPGlEPTB;MU[uNVIxKMLzIESuNFAyKM7:TR?= MoXlNlM2PDZ3OUG=
Huh7 NG\xWlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkC4OFghcA>? NGThN3RKSzVyPUG1MlAxPyEEsTC3MlM{PCEQvF2= NEToOm4zOzV2NkW5NS=>
HepG2 MkjYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVPlXXpyPzJiaB?= MlvpTWM2OD1zLkKwNEDDuSByLkKyOkDPxE1? MYSyN|U1PjV7MR?=
Hep3B NIfW[ndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkC2O|IhcA>? M3LoPGlEPTB;MD64PVIhyrFiMD6wOFQh|ryP M1PpWVI{PTR4NUmx
PLC/PRF5 NHixbGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVu3[nBTPzJiaB?= MYnJR|UxRTNwMUGwJOKyKDBwM{O3JO69VQ>? NED0RmwzOzV2NkW5NS=>
Huh7 NIjLeZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY[yUJNNPzJiaB?= M3XMS2lEPTB;Mz65PFAhyrFiMD64NFMh|ryP NYLFVXJMOjN3NE[1PVE>
MFE280 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmGzTWM2OD1yLkSyJOKyKDBwME[g{txO NIOwTJIzOzR2M{iwOS=>
AN3CA NEnuXXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHGxZZlKSzVyPUCuOVAhyrFiMD6xNEDPxE1? MYKyN|Q1OzhyNR?=
HEC155 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVnVd|ByUUN3ME2wMlY3KMLzIECuNFkh|ryP NFmy[3MzOzR2M{iwOS=>
MFE296 MnWxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHqTWM2OD1yLk[2JOKyKDBwMUmg{txO Ml;MNlM1PDN6MEW=
SPAC1S NXWyfodET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTBwN{egxtEhOC5yODFOwG0> MVSyN|Q1OzhyNR?=
RL952 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV7I[|dHUUN3ME2wMlk{KMLzIECuNFEh|ryP NVLBTGVwOjN2NEO4NFU>
EN1 MkDBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYTMb2F{UUN3ME2xMlAzKMLzIECuNlUh|ryP NXXkUYhvOjN2NEO4NFU>
SNGII MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkXOTWM2OD1zLkK0JOKyKDBwMkig{txO MkLLNlM1PDN6MEW=
ISHIKAWA MorqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYnJR|UxRTFwM{CgxtEhOC5zMTFOwG0> MXeyN|Q1OzhyNR?=
HEC1A MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYro[JJIUUN3ME2xMlM1KMLzIECuN|Ah|ryP NGT5S5MzOzR2M{iwOS=>
KLE Mm\qS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fnd2lEPTB;MT6zO{DDuSByLkCyJO69VQ>? M1frPFI{PDR|OEC1
SNGM MkftS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M17OTmlEPTB;MT60NkDDuSByLkGzJO69VQ>? MXWyN|Q1OzhyNR?=
USPC2 M1q1dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTFwNkKgxtEhOC5yMTFOwG0> M1TkflI{PDR|OEC1
EN NW[0cndbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MonxTWM2OD1zLk[2JOKyKDBwMEGg{txO NHfuN4czOzR2M{iwOS=>
MFE319 M3\Wc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTFwOEegxtEhOC52NTFOwG0> NIqxNZgzOzR2M{iwOS=>
EFE184 MnHIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnTtTWM2OD1{LkC0JOKyKDBwMUOg{txO MWqyN|Q1OzhyNR?=
ECC1 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1fn[mlEPTB;Mj6wO{DDuSByLkCxJO69VQ>? M2jNb|I{PDR|OEC1
HEC1B MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkTpTWM2OD1{LkW3JOKyKDBwMkOg{txO MofzNlM1PDN6MEW=
USPC1 M4O4bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIHLZW9KSzVyPUKuOlAhyrFiMD6xN{DPxE1? MnHDNlM1PDN6MEW=
SPAC1L M4DYO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnfFTWM2OD1|LkC2JOKyKDFwMUSg{txO MUeyN|Q1OzhyNR?=
HUVEC MW\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NF7LfFkxNTJ3IN88US=> MX63NkBp NYnyXGo3TE2VTx?= NELmVFdqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NXXUbGVKOjN{MkiwNVc>
HMVEC NH3ReWhE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NEH3TlUxNTJ3IN88US=> NIP3fZY4OiCq NV:ycXFtTE2VTx?= MW\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> Mmr6NlMzOjhyMUe=
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Sk-Hep1 NFfrRWtCeG:ydH;zbZMhSXO|YYm= MUCwMVEzNjVizszN NYTWS|FuOjRiaB?= NWnqVYp1TE2VT9Mg NXLHUYc3e2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? MUeyNlI{ODR5OR?=
Hep3B NULoZXpCSXCxcITvd4l{KEG|c3H5 MW[wMVEzNjVizszN NXfaeJpNOjRiaB?= M{PKWmROW00EoB?= NXjmbXNCe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NFPke|czOjJ|MES3PS=>
PLC5 MmHKRZBweHSxc3nzJGF{e2G7 NH2wcIoxNTF{LkWg{txO NEXOV2YzPCCq NES5VWhFVVORwrC= Ml\0d4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> M1vxVVIzOjNyNEe5
PLC5 NYHLOFB6S2WubDDWbYFjcWyrdImgRZN{[Xl? NXP3foVGOC1zNTFOwG0> MUS3NkBp Mlf5doVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MmewNlIyQDB|MEi=
Hep3B NXLPWGdkS2WubDDWbYFjcWyrdImgRZN{[Xl? NIP4WYoxNTF3IN88US=> NW\qb2N3PzJiaB?= MYLy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MlOzNlIyQDB|MEi=
Sk-Hep1 NHTHV2JE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NEfwdnQxNTF3IN88US=> M4X2R|czKGh? MYTy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NITMcnkzOjF6MEOwPC=>
Huh-7 M{HQUWNmdGxiVnnhZoltcXS7IFHzd4F6 MnT6NE0yPSEQvF2= MYO3NkBp MmnvdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M3\vUVIzOThyM{C4
PLC5 NUjIXml4SXCxcITvd4l{KEG|c3H5 MYiwMVE2KM7:TR?= NGLwXmMzPCCq NVnmOIFLcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MVOyNlE5ODNyOB?=
Hep3B NXP2[WJ5SXCxcITvd4l{KEG|c3H5 MmW5NE0yPSEQvF2= M2PYUFI1KGh? NIjWb25qdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= M1vJWFIzOThyM{C4
Sk-Hep1 M3fudGFxd3C2b4Ppd{BCe3OjeR?= Mk\kNE0yPSEQvF2= MnfMNlQhcA>? NXPpZnM6cW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= M1rCdVIzOThyM{C4
Huh-7 Moj3RZBweHSxc3nzJGF{e2G7 MnT0NE0yPSEQvF2= M37EVlI1KGh? MoLsbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MkPGNlIyQDB|MEi=
PLC5 M3jtSWZ2dmO2aX;uJGF{e2G7 NWrh[XhlOC1zMDFOwG0> NXrnSoZ5OjRiaB?= NHX6SIpk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NUTBXFd[OjJzOECzNFg>
Hep3B MUDGeY5kfGmxbjDBd5NigQ>? NYTJW29WOC1zMDFOwG0> NF;lV5EzPCCq M3XFRoNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? NWfLWWZZOjJzOECzNFg>
Sk-Hep1 MY\GeY5kfGmxbjDBd5NigQ>? NX3pdJFCOC1zMDFOwG0> MlizNlQhcA>? M4PMOoNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? NXXZ[pZ5OjJzOECzNFg>
Huh-7 NUjWO216TnWwY4Tpc44hSXO|YYm= MmHQNE0yOCEQvF2= MlLQNlQhcA>? M3TxPYNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? M1LEZVIzOThyM{C4
SW780 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXe1JIQ> M1iyUmlEPTB;NUCgcm0> NGnr[m8zOTFzOU[2NS=>
RT112 NH7JRlBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mlj0OUBl MkOxTWM2OD1zNTDuUS=> MmL4NlEyOTl4NkG=
RT4 M2nwVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4roOFUh\A>? MVLJR|UxRTVibl2= MYSyNVEyQTZ4MR?=
JMSU1 M4HC[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjPeFFNPSCm M1PGTmlEPTB;NUCgcm0> NIKwc48zOTFzOU[2NS=>
J82 M{mxWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nSW|Uh\A>? NFS4WGpKSzVyPUG0NFAhdk1? M{PzTFIyOTF7Nk[x
97-7 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrUepg2KGR? MlviTWM2OD1zMECwJI5O Mn;sNlEyOTl4NkG=
RT112 M1\nZWZ2dmO2aX;uJGF{e2G7 NYTXNot7PTByIH7N MUOyOEBp MoTqbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| Mle5NlEyOTl4NkG=
RT4 MnzPSpVv[3Srb36gRZN{[Xl? M1HEfFUxOCCwTR?= NH\vc2IzPCCq MVXpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? MYKyNVEyQTZ4MR?=
MGH-U3 NVu0c4pGTnWwY4Tpc44hSXO|YYm= MXu1NFAhdk1? M1flO|I1KGh? NYr2Umx6cW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz MWKyNVEyQTZ4MR?=
SW780 MmrmSpVv[3Srb36gRZN{[Xl? MkXUOVAxKG6P M3rnWFI1KGh? MmfjbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| M2H4[lIyOTF7Nk[x
97-7 NGXqRY1HfW6ldHnvckBCe3OjeR?= NYXDXoZOPTByIH7N M2HGZ|I1KGh? NIrY[5ZqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= NYHvVJhEOjFzMUm2OlE>
 J807C NVHsRnVKS2WubDDWbYFjcWyrdImgRZN{[Xl? MWGwMVQxOCCwTR?= NIH5OYw1QCCq Mn;obY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NUHEXXpIOTV3OUi4NVQ>
Y373C NHXveoFE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MY[wMVQxOCCwTR?= M2nJVFQ5KGh? MknWbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NXnyfGY6OTV3OUi4NVQ>
K650E NG\BRWFE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M2LZUlAuPDByIH7N MVi0PEBp Ml\NbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NWjVZ5BiOTV3OUi4NVQ>
G384D M3X3XWNmdGxiVnnhZoltcXS7IFHzd4F6 Ml:3NE01ODBibl2= NHz3[ZE1QCCq M1LHe4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NEPWVYoyPTV7OEixOC=>
F384L MWPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MkTxNE01ODBibl2= NXHje41GPDhiaB?= MknFbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NFXjXlUyPTV7OEixOC=>
KMS11 NGPwW4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17xO|czKGh? MojCTWM2OD17MDDuUS=> MXyxOVU6QDhzNB?=
KMS18 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYG3NkBp NVjGbpBOUUN3ME21OVAhdk1? M3jmNlE2PTl6OEG0
OPM2 M{\CZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjBO|IhcA>? MXPJR|UxRTlyIH7N NF3lcVQyPTV7OEixOC=>
H929 NWPpbIlVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mo[0O|IhcA>? NInpTWpKSzVyPjCyOVAxKG6P NF\CZnAyPTV7OEixOC=>
8226 M3XHcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;XZlczKGh? NUHSSo05UUN3ME6gNlUxOCCwTR?= NEDrXI0yPTV7OEixOC=>
U266 MnqyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUC3NkBp Mn\wTWM2OD5iMkWwNEBvVQ>? M3r3VFE2PTl6OEG0

... 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 slightly soluble or insoluble
Ethanol slightly soluble or insoluble
In vivo Add solvents individually and in order:
30% PEG400+0.5% Tween80+5% propylene glycol
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 392.43
Formula

C21H21FN6O

CAS No. 405169-16-6
Storage powder
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