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 NEHLfIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWfCeoZDUUN3ME2wMlQ1QSEQvF2= MoXDNlUzODJyN{O=
SupB15-R NHjOd4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIfOeIxKSzVyPUCuOVU5KM7:TR?= NYGwW|hHOjV{MEKwO|M>
BaF3-pSRα NUjLc2IzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGjqWnZKSzVyPUCuOlY5KM7:TR?= NXyxVmtzOjV{MEKwO|M>
BaF3-p210Bcr-Abl M1;YfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkDFTWM2OD1yLk[5NkDPxE1? NUDaOXRMOjV{MEKwO|M>
BaF3-p210Bcr-Abl-T315I MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH73U3hKSzVyPUKuOlI3KM7:TR?= NGHZeHIzPTJyMkC3Ny=>
CCRF-CEM MmfOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLzeHF[UUN3ME2wMlM6QCEQvF2= Mm\5NlUzODJyN{K=
CEM/C2 NVLjcIdNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn;aTWM2OD1zLkGyOUDPxE1? MnPMNlUzODJyN{K=
Nalm-6 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWfJR|UxRTBwM{iyJO69VQ>? NFLMV3EzPTJyMkC3Ni=>
SEM-K2 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nLTmlEPTB;MD6wNlIh|ryP NFPSRpEzPTJyMkC3Ni=>
HB-1119 Mn6xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnHnTWM2OD1yLkCyPEDPxE1? NIrxd4kzPTJyMkC3Ni=>
RS4:11 M3vHZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjEZXE1UUN3ME2yMlgyKM7:TR?= M2HsblI2OjB{MEey
Nalm-6 M3PJOGFxd3C2b4Ppd{BCe3OjeR?= MWOyJO69VQ>? M17UPVI1NzR6IHi= M{T1ZYlv\HWlZYOgZZBweHSxc3nzJJJme3WudHnu[{BqdiCjYn;1eEA4OiVib3[gZ4VtdCCmZXH0bEBi\nSncjCyOEBpKHS{ZXH0cYVvfCCjbnSgPFEmKGGodHXyJFQ5KGh? NEfCRY0zPTJyMkC3Ni=>
SEM-K2 MWLBdI9xfG:|aYOgRZN{[Xl? MVqwMlEwOSEQvF2= MmG0NlQhcA>? MX\pcoR2[2W|IHXhdox6KGGyb4D0c5NqeyCxZjDTSW0uUzJiY3XscJMh[XRiMD6xJO69VSCjZoTldkAzPCCq MkfCNlUzODJyN{K=
HCT-116 NVTzPGpiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYjJR|UxRTNwMEWwMlU5KM7:TR?= MViyOFQ6PTd3MB?=
HT-29 MkL3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTVwMkGuPVMh|ryP MnzUNlQ1QTV5NUC=
SW-480 MnjWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4OwV2lEPTB;ND6zN|AvPDdizszN MV2yOFQ6PTd3MB?=
CaCO2 NEn4[IJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnXTYhKSzVyPUOuNlMxNjZ2IN88US=> Mn60NlQ1QTV5NUC=
LS174T MlTQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DXSGlEPTB;ND6zN|AvPDdizszN MmjjNlQ1QTV5NUC=
HEC-1A NIm0Rm1HfW6ldHnvckBCe3OjeR?= MYOwMlA2NzBwMT:wMlUh|ryP NGLmVlI4OiCq M{LPToNifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v M2PJNVI1PDl3N{Ww
AN3CA Mo\MSpVv[3Srb36gRZN{[Xl? MXqwMlA2NzBwMT:wMlUh|ryP MUG3NkBp M17S[4NifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v MlzNNlQ1QTV5NUC=
MFE-296  MYDGeY5kfGmxbjDBd5NigQ>? MWWwMlA2NzBwMT:wMlUh|ryP M1LZO|czKGh? NHPw[ZFk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? NF;XOpAzPDR7NUe1NC=>
UMC3 NIC3dmVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MknJNU0yOCEQvF2= NWPjSI9RPzJiaB?= NW\DW3NlcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MV2yOFMzPTR4MR?=
5637 MXrD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NF\LOmcyNTFyIN88US=> MnjVO|IhcA>? MUnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M1nYOlI1OzJ3NE[x
HU456 M4nzUWNmdGxiVnnhZoltcXS7IFHzd4F6 NV7Xdo97OS1zMDFOwG0> NWT5fno2PzJiaB?= MVrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NGmye4wzPDN{NUS2NS=>
MGHU4 MUDD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NEi3eVUyNTFyIN88US=> NHXON2M4OiCq M2TzSYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MmHYNlQ{OjV2NkG=
HT1376 MWrD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3LDVVEuOTBizszN NVuzdZJIPzJiaB?= NVnhSI05cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NHXIZWUzPDN{NUS2NS=>
RT112 MmXsR4VtdCCYaXHibYxqfHliQYPzZZk> MnPNNU0yOCEQvF2= Mm\3O|IhcA>? M{jIfYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MVGyOFMzPTR4MR?=
T24 MYLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MmLNNU0yOCEQvF2= MX63NkBp NGfqRZNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MoPYNlQ{OjV2NkG=
BFTC905 NG[wc3VE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MoTBNU0yOCEQvF2= M4\kXVczKGh? M1z6fYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MmG0NlQ{OjV2NkG=
TCC-SUP NHG4PZVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVzTUZZYOS1zMDFOwG0> NETidlA4OiCq Mnr5bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NVrLc496OjR|MkW0OlE>
RT4 NWnROlZOS2WubDDWbYFjcWyrdImgRZN{[Xl? MlLjNU0yOCEQvF2= NWq5b5FqPzJiaB?= NFTiVYtqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M1TqOlI1OzJ3NE[x
HONE1 M4DNUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPBeJkxNjFvMUCg{txO MUC0POKhcA>? NFXtNmdqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NGHyR|gzPDJ|OEC5OC=>
HNE1 MmDkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmq2NE4yNTFyIN88US=> NV:5eZJiPDkEoHi= MnTEbY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy MnnFNlQzOzhyOUS=
CNE2  Mo\LS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkO0NE4yNTFyIN88US=> NISzT2Q1QMLiaB?= NIjnXFhqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MVGyOFI{QDB7NB?=
C666-1 NGL3TWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M37vSVAvOS1zMDFOwG0> NG\BR2k1QMLiaB?= NE\EdndqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NGOyWpUzPDJ|OEC5OC=>
HeLa MkLMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmLiNE4yNTFyIN88US=> NVPNT3BNOjRiaB?= M3fBU4lv\HWlZYOgS|IwVSCjcoLld5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NX3FeHBKOjR{M{iwPVQ>
Hep3B M4HZWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGH3U2wxNjFvMUCg{txO M1TyeFI1KGh? NWLNXGJ3cW6mdXPld{BIOsLiYYLy[ZN1yqB? MnruNlQzOzhyOUS=
HepG2 NUPidHRQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlTYOFghcA>? NWKwU3lCUUN3ME2yMlczPyEEsTCwMlQzQSEQvF2= M33HR|I{PTR4NUmx
Hep3B MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXX4cpVUPDhiaB?= M2nud2lEPTB;ND6yNlMhyrFiMD64N|kh|ryP MnXLNlM2PDZ3OUG=
PLC/PRF5 MmWzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlPZOFghcA>? NGXlSmxKSzVyPUG2MlEzOCEEsTC0MlAxOSEQvF2= NEPDfJgzOzV2NkW5NS=>
Huh7 Mkj6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUS0PEBp NXzwZZRrUUN3ME2xOU4xODdiwsGgO{4{OzRizszN Mn\BNlM2PDZ3OUG=
HepG2 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXrBc3JbPzJiaB?= MYHJR|UxRTFwMkCwJOKyKDBwMkK2JO69VQ>? NVjkT5Z3OjN3NE[1PVE>
Hep3B MljiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4ewSFczKGh? MXXJR|UxRTBwOEmyJOKyKDBwMES0JO69VQ>? NFLJT5ozOzV2NkW5NS=>
PLC/PRF5 NVnaWFU6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrrUIw5PzJiaB?= NH;qXGhKSzVyPUOuNVExKMLzIECuN|M4KM7:TR?= M373RVI{PTR4NUmx
Huh7 M4LJU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnjUlA4OiCq NUfGV5F1UUN3ME2zMlk5OCEEsTCwMlgxOyEQvF2= MVyyN|U1PjV7MR?=
MFE280 MnftS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWrUbJhwUUN3ME2wMlQzKMLzIECuNFYh|ryP M3ftN|I{PDR|OEC1
AN3CA NGLYXVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXyzTnF3UUN3ME2wMlUxKMLzIECuNVAh|ryP MWWyN|Q1OzhyNR?=
HEC155 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mm\MTWM2OD1yLk[2JOKyKDBwMEmg{txO NXvIWZZVOjN2NEO4NFU>
MFE296 M{fiXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXvrcHNkUUN3ME2wMlY3KMLzIECuNVkh|ryP M3i0SVI{PDR|OEC1
SPAC1S NEK1c2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkTjTWM2OD1yLke3JOKyKDBwMEig{txO NWWzd5gxOjN2NEO4NFU>
RL952 M2nQWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnab|NKSzVyPUCuPVMhyrFiMD6wNUDPxE1? NYLWR3JyOjN2NEO4NFU>
EN1 M4fVTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFKzTZJKSzVyPUGuNFIhyrFiMD6yOUDPxE1? NVTRTnpPOjN2NEO4NFU>
SNGII NYfySY1FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3qxNWlEPTB;MT6yOEDDuSByLkK4JO69VQ>? MlvGNlM1PDN6MEW=
ISHIKAWA M3X2U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTFwM{CgxtEhOC5zMTFOwG0> NX;nRldIOjN2NEO4NFU>
HEC1A MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1PFPWlEPTB;MT6zOEDDuSByLkOwJO69VQ>? NHLWSmgzOzR2M{iwOS=>
KLE NFviVWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIHNXmZKSzVyPUGuN|chyrFiMD6wNkDPxE1? MVmyN|Q1OzhyNR?=
SNGM NEjmNYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIfmV|ZKSzVyPUGuOFIhyrFiMD6xN{DPxE1? MX[yN|Q1OzhyNR?=
USPC2 NVLBcXNwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;nfItXUUN3ME2xMlYzKMLzIECuNFEh|ryP NVnQfYZGOjN2NEO4NFU>
EN M2njTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NELyTFhKSzVyPUGuOlYhyrFiMD6wNUDPxE1? M1PpTVI{PDR|OEC1
MFE319 NUjLO25YT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHyySGRKSzVyPUGuPFchyrFiMD60OUDPxE1? NXLue4duOjN2NEO4NFU>
EFE184 NFHJ[nNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmjzTWM2OD1{LkC0JOKyKDBwMUOg{txO NVnk[nk4OjN2NEO4NFU>
ECC1 NUnKZ2h[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\LdXFKSzVyPUKuNFchyrFiMD6wNUDPxE1? MYqyN|Q1OzhyNR?=
HEC1B MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmG1TWM2OD1{LkW3JOKyKDBwMkOg{txO NXniR29LOjN2NEO4NFU>
USPC1 NGPIdWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPu[ZZyUUN3ME2yMlYxKMLzIECuNVMh|ryP NXLnfmJtOjN2NEO4NFU>
SPAC1L MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX;JR|UxRTNwME[gxtEhOS5zNDFOwG0> M4qyS|I{PDR|OEC1
HUVEC NIj4TJZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M2fsSlAuOjVizszN NVzqXXBDPzJiaB?= NF;sRmRFVVOR MV3pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NEX3V|YzOzJ{OECxOy=>
HMVEC Ml;hR4VtdCCYaXHibYxqfHliQYPzZZk> MUKwMVI2KM7:TR?= NFf4fo04OiCq MlrZSG1UVw>? MV;pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MkTZNlMzOjhyMUe=
MHCC-97H MWjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MnvuNE0zPSEQvF2= MXK3NkBp M2XlXmROW09? NGnSeIFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M2LTTVI{OjJ6MEG3
SMMC7721 NVXkblQxS2WubDDWbYFjcWyrdImgRZN{[Xl? MnXhNE0zPSEQvF2= NEK1Zmg4OiCq M3PDb2ROW09? NVWwZ2plcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MUKyN|IzQDBzNx?=
Huh-7 MY\BdI9xfG:|aYOgRZN{[Xl? NXfZUJIxOC1zMj61JO69VQ>? NXrnWoo5OjRiaB?= M4mxSWROW00EoB?= MWfz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NI[wPW4zOjJ|MES3PS=>
Sk-Hep1 MojBRZBweHSxc3nzJGF{e2G7 MorsNE0yOi53IN88US=> NWTx[2FnOjRiaB?= MWrEUXNQyqB? NFXLU5p{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz MW[yNlI{ODR5OR?=
Hep3B Mn7nRZBweHSxc3nzJGF{e2G7 MVGwMVEzNjVizszN NHz0OY8zPCCq MXTEUXNQyqB? Mn;td4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> M1;UdVIzOjNyNEe5
PLC5 NYeyPIs6SXCxcITvd4l{KEG|c3H5 M4HRVFAuOTJwNTFOwG0> NH[2SYczPCCq NUe3doJlTE2VT9Mg Mn;Ld4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> MmTJNlIzOzB2N{m=
PLC5 NVLFbopkS2WubDDWbYFjcWyrdImgRZN{[Xl? NYnrUmhIOC1zNTFOwG0> NH;FZoM4OiCq M{Pu[ZJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NF3ObZEzOjF6MEOwPC=>
Hep3B MYfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NHj0clcxNTF3IN88US=> M{X4eFczKGh? M2Sy[JJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MVOyNlE5ODNyOB?=
Sk-Hep1 M2jjdWNmdGxiVnnhZoltcXS7IFHzd4F6 NFjiNWMxNTF3IN88US=> M4TyXVczKGh? MULy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MlX0NlIyQDB|MEi=
Huh-7 M3rKdmNmdGxiVnnhZoltcXS7IFHzd4F6 MWSwMVE2KM7:TR?= NYDmbmM{PzJiaB?= NES1UZNz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NVGwToFDOjJzOECzNFg>
PLC5 NIrrTmFCeG:ydH;zbZMhSXO|YYm= NYLEd|hMOC1zNTFOwG0> M1:yZVI1KGh? NVnzXnFLcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MXSyNlE5ODNyOB?=
Hep3B M4ni[2Fxd3C2b4Ppd{BCe3OjeR?= M4XofFAuOTVizszN NGTEN2ozPCCq M2LD[Ilv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MWmyNlE5ODNyOB?=
Sk-Hep1 MmHwRZBweHSxc3nzJGF{e2G7 MnvUNE0yPSEQvF2= M3ToO|I1KGh? NUPwfYk3cW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MWmyNlE5ODNyOB?=
Huh-7 M3Lp[2Fxd3C2b4Ppd{BCe3OjeR?= Mk[wNE0yPSEQvF2= NGnSbG4zPCCq MXTpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? M1P0[FIzOThyM{C4
PLC5 MX;GeY5kfGmxbjDBd5NigQ>? MV2wMVExKM7:TR?= NFriOI8zPCCq MmfIZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v MW[yNlE5ODNyOB?=
Hep3B NInuUlJHfW6ldHnvckBCe3OjeR?= MnrlNE0yOCEQvF2= NYHsXpFIOjRiaB?= NH24OINk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? MWKyNlE5ODNyOB?=
Sk-Hep1 M13FdmZ2dmO2aX;uJGF{e2G7 NIfYUYsxNTFyIN88US=> NF\4SYQzPCCq NFnZeHJk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? Ml7iNlIyQDB|MEi=
Huh-7 M4LPc2Z2dmO2aX;uJGF{e2G7 M{f1XFAuOTBizszN M1v3TlI1KGh? M2m1V4NifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? Moi0NlIyQDB|MEi=
SW780 M2rNZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV21JIQ> Mk\ZTWM2OD13MDDuUS=> MUiyNVEyQTZ4MR?=
RT112 NWjhRYR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrWPXN7PSCm MmXSTWM2OD1zNTDuUS=> M2LBXVIyOTF7Nk[x
RT4 NVLsfWYyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH76O5M2KGR? M2XPZmlEPTB;NTDuUS=> NHHa[lkzOTFzOU[2NS=>
JMSU1 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVjmZ|V{PSCm NIHPXW5KSzVyPUWwJI5O MXKyNVEyQTZ4MR?=
J82 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzYT4c2KGR? MY\JR|UxRTF2MECgcm0> NFP3ZmwzOTFzOU[2NS=>
97-7 NIKxV3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVy1JIQ> M3XTeWlEPTB;MUCwNEBvVQ>? MUmyNVEyQTZ4MR?=
RT112 NGO2dXFHfW6ldHnvckBCe3OjeR?= NHqxeoo2ODBibl2= NYTGbG1iOjRiaB?= NVrXRmx[cW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz NWnGSnN1OjFzMUm2OlE>
RT4 MXXGeY5kfGmxbjDBd5NigQ>? MnfaOVAxKG6P NX\RVWFtOjRiaB?= M1frZ4lv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= NUfiO|hUOjFzMUm2OlE>
MGH-U3 M{\zV2Z2dmO2aX;uJGF{e2G7 MoPqOVAxKG6P MlWxNlQhcA>? MnfSbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NH;TOHozOTFzOU[2NS=>
SW780 MnrYSpVv[3Srb36gRZN{[Xl? NEjoVIw2ODBibl2= MmPGNlQhcA>? MWTpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NEfBO|EzOTFzOU[2NS=>
97-7 NX[5VZpCTnWwY4Tpc44hSXO|YYm= MXK1NFAhdk1? MknkNlQhcA>? NILNVIlqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= NHnic24zOTFzOU[2NS=>
 J807C NUjEb21VS2WubDDWbYFjcWyrdImgRZN{[Xl? NVXqNWt3OC12MECgcm0> NWfSb4k6PDhiaB?= MVTpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MVyxOVU6QDhzNB?=
Y373C NH7odGZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NXPs[mhSOC12MECgcm0> NH\tT3g1QCCq MnK3bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MVKxOVU6QDhzNB?=
K650E M2H2WmNmdGxiVnnhZoltcXS7IFHzd4F6 NITmeo0xNTRyMDDuUS=> M1\yflQ5KGh? MXzpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MWSxOVU6QDhzNB?=
G384D NYrBeWNXS2WubDDWbYFjcWyrdImgRZN{[Xl? MkTUNE01ODBibl2= MVe0PEBp M3zFc4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NGrxcG8yPTV7OEixOC=>
F384L NVjv[XFuS2WubDDWbYFjcWyrdImgRZN{[Xl? M4TQb|AuPDByIH7N NEjrWHI1QCCq NFW1WmFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M3fPNFE2PTl6OEG0
KMS11 NX20d4pXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVq3NkBp NX\5VGJRUUN3ME25NEBvVQ>? MmXCNVU2QTh6MUS=
KMS18 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX65UZkzPzJiaB?= NF3xRWxKSzVyPUW1NEBvVQ>? NIH4W5YyPTV7OEixOC=>
OPM2 MlO5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV[3NkBp MWLJR|UxRTlyIH7N NEfrcWMyPTV7OEixOC=>
H929 MoraS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7pXGc4OiCq NIqy[5FKSzVyPjCyOVAxKG6P MWWxOVU6QDhzNB?=
8226 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUfiS5E{PzJiaB?= NILkb|VKSzVyPjCyOVAxKG6P MorZNVU2QTh6MUS=
U266 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlnSO|IhcA>? NUPHS49mUUN3ME6gNlUxOCCwTR?= NH3le4kyPTV7OEixOC=>

... 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
NCT02268435 Withdrawn Gastrointestinal Stromal Tumors Asan Medical Center March 2015 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
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 28 2014 Phase 2|Phase 3
NCT01994590 Terminated Prostate Cancer M.D. Anderson Cancer Center|Novartis May 19 2014 Phase 2
NCT01972750 Unknown status First or Second Recurrence of Glioblastoma PD Dr. Martin Glas|University Hospital Bonn October 2013 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