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 MnPYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PFOWlEPTB;MD60OFkh|ryP NIHuPGQzPTJyMkC3Ny=>
SupB15-R NVjzeohST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDDZ4RRUUN3ME2wMlU2QCEQvF2= NFPPOWgzPTJyMkC3Ny=>
BaF3-pSRα MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPFTWM2OD1yLk[2PEDPxE1? M1L5VVI2OjB{MEez
BaF3-p210Bcr-Abl M3;Ccmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzHSZVKSzVyPUCuOlkzKM7:TR?= MnzDNlUzODJyN{O=
BaF3-p210Bcr-Abl-T315I M{jKb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NW\jd5h{UUN3ME2yMlYzPiEQvF2= NWiyRpN5OjV{MEKwO|M>
CCRF-CEM NWrweItjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjLUFJKSzVyPUCuN|k5KM7:TR?= NUXlXnQzOjV{MEKwO|I>
CEM/C2 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX3JR|UxRTFwMUK1JO69VQ>? NXX2NJdHOjV{MEKwO|I>
Nalm-6 MmDFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTBwM{iyJO69VQ>? MoD3NlUzODJyN{K=
SEM-K2 MlzqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\FTWM2OD1yLkCyNkDPxE1? NEG0eo4zPTJyMkC3Ni=>
HB-1119 NV;6OZZDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYfJR|UxRTBwMEK4JO69VQ>? NXjF[FBzOjV{MEKwO|I>
RS4:11 NXrhbJB4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHNSnZyUUN3ME2yMlgyKM7:TR?= M1f3WlI2OjB{MEey
Nalm-6 MUTBdI9xfG:|aYOgRZN{[Xl? MnXMNkDPxE1? M2n6WFI1NzR6IHi= MlzabY5lfWOnczDhdI9xfG:|aYOgdoV{fWy2aX7nJIlvKGGkb4X0JFczLSCxZjDj[YxtKGSnYYToJIFnfGW{IEK0JIghfHKnYYTt[Y51KGGwZDC4NUUh[W[2ZYKgOFghcA>? NF\jXJczPTJyMkC3Ni=>
SEM-K2 MoK4RZBweHSxc3nzJGF{e2G7 MYmwMlEwOSEQvF2= MVKyOEBp NVSySWJPcW6mdXPld{Bm[XKueTDhdI9xfG:|aYOgc4YhW0WPLVuyJINmdGy|IHH0JFAvOSEQvF2gZYZ1\XJiMkSgbC=> NH60RnkzPTJyMkC3Ni=>
HCT-116 M3TaWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUDydIY6UUN3ME2zMlA2OC53ODFOwG0> NY\B[VVKOjR2OUW3OVA>
HT-29 MlfBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXzJR|UxRTVwMkGuPVMh|ryP NV3XclBSOjR2OUW3OVA>
SW-480 NHiwcWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX7nR2dSUUN3ME20MlM{OC52NzFOwG0> MYWyOFQ6PTd3MB?=
CaCO2 MmHOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3y1PWlEPTB;Mz6yN|AvPjRizszN M1v6OVI1PDl3N{Ww
LS174T NEjJcZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY[wcHZjUUN3ME20MlM{OC52NzFOwG0> MkfUNlQ1QTV5NUC=
HEC-1A M3HWTGZ2dmO2aX;uJGF{e2G7 NWLi[HpCOC5yNT:wMlEwOC53IN88US=> MnrmO|IhcA>? M{HtSINifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v M4\tblI1PDl3N{Ww
AN3CA NWiyXW5QTnWwY4Tpc44hSXO|YYm= Ml3iNE4xPS9yLkGvNE42KM7:TR?= NXq1[XV2PzJiaB?= MnvmZ4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> MYCyOFQ6PTd3MB?=
MFE-296  MXjGeY5kfGmxbjDBd5NigQ>? NUPLU|lwOC5yNT:wMlEwOC53IN88US=> MoD3O|IhcA>? MUjjZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> MorwNlQ1QTV5NUC=
UMC3 MXPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MX6xMVExKM7:TR?= M4m2UlczKGh? MUDpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NHLuUYgzPDN{NUS2NS=>
5637 M2\IdmNmdGxiVnnhZoltcXS7IFHzd4F6 MkPRNU0yOCEQvF2= MnvBO|IhcA>? MYnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MV:yOFMzPTR4MR?=
HU456 Ml7HR4VtdCCYaXHibYxqfHliQYPzZZk> MXyxMVExKM7:TR?= M2TRT|czKGh? Mn3HbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MXiyOFMzPTR4MR?=
MGHU4 NF7ZOGVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NIXRd2cyNTFyIN88US=> MmPyO|IhcA>? MWrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MVGyOFMzPTR4MR?=
HT1376 NHX6W4dE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1jlNlEuOTBizszN NVy5V|N1PzJiaB?= Mo\0bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NVPKeY1UOjR|MkW0OlE>
RT112 M3TGNmNmdGxiVnnhZoltcXS7IFHzd4F6 NUjlO|ZHOS1zMDFOwG0> NFn5WY84OiCq M1jyOolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M4jNOlI1OzJ3NE[x
T24 NYW1fopFS2WubDDWbYFjcWyrdImgRZN{[Xl? NGroZ48yNTFyIN88US=> M1\4dlczKGh? Mnv5bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MnH5NlQ{OjV2NkG=
BFTC905 MX;D[YxtKF[rYXLpcIl1gSCDc4PhfS=> M{XBblEuOTBizszN M2X6WFczKGh? NFS0dpdqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M3v2[lI1OzJ3NE[x
TCC-SUP NVHnPFRVS2WubDDWbYFjcWyrdImgRZN{[Xl? NVvlc3loOS1zMDFOwG0> MYC3NkBp M3fE[YlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NFXjPGQzPDN{NUS2NS=>
RT4 MV7D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NF3KZ3kyNTFyIN88US=> M{DHV|czKGh? M374U4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MW[yOFMzPTR4MR?=
HONE1 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDFNE4yNTFyIN88US=> M{HyWFQ5yqCq MXrpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= NHLOdmwzPDJ|OEC5OC=>
HNE1 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MofYNE4yNTFyIN88US=> Mme1OFjDqGh? MXrpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MXuyOFI{QDB7NB?=
CNE2  NFHZRW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYTZepNiOC5zLUGwJO69VQ>? M321e|Q5yqCq MkHXbY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy NFL6Z|AzPDJ|OEC5OC=>
C666-1 MkOwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV2wMlEuOTBizszN M370VVQ5yqCq MWfpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= NV\1OJNPOjR{M{iwPVQ>
HeLa NEXJdplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXi4Z2ZqOC5zLUGwJO69VQ>? NUP1cINnOjRiaB?= NYjyV3hXcW6mdXPld{BIOi:PIHHydoV{fCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M2Xye|I1OjN6MEm0
Hep3B NE[2WY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH\wflExNjFvMUCg{txO NUTTO2hvOjRiaB?= MX7pcoR2[2W|IFeyxsBienKnc4VCpC=> MYGyOFI{QDB7NB?=
HepG2 NVzjTFM3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{T3dlQ5KGh? NIT6b45KSzVyPUKuO|I4KMLzIECuOFI6KM7:TR?= M2nnOFI{PTR4NUmx
Hep3B M13wbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2\ZXFQ5KGh? M3PHNGlEPTB;ND6yNlMhyrFiMD64N|kh|ryP MnLJNlM2PDZ3OUG=
PLC/PRF5 M1zCTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NELUVJQ1QCCq NV3UXnY1UUN3ME2xOk4yOjBiwsGgOE4xODFizszN NFvXTGEzOzV2NkW5NS=>
Huh7 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2fqfFQ5KGh? MUXJR|UxRTF3LkCwO{DDuSB5LkOzOEDPxE1? NXzYfZJ2OjN3NE[1PVE>
HepG2 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Moq3O|IhcA>? M{DzW2lEPTB;MT6yNFAhyrFiMD6yNlYh|ryP NIToVIszOzV2NkW5NS=>
Hep3B M4ji[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1PtblczKGh? NIH4cJFKSzVyPUCuPFkzKMLzIECuNFQ1KM7:TR?= MUKyN|U1PjV7MR?=
PLC/PRF5 M4jDcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWK3NkBp NFjZSYVKSzVyPUOuNVExKMLzIECuN|M4KM7:TR?= NGK3R4gzOzV2NkW5NS=>
Huh7 NVHT[nM6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4DYN|czKGh? MVXJR|UxRTNwOUiwJOKyKDBwOECzJO69VQ>? MofJNlM2PDZ3OUG=
MFE280 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{e5SmlEPTB;MD60NkDDuSByLkC2JO69VQ>? Mnv2NlM1PDN6MEW=
AN3CA MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrSTWM2OD1yLkWwJOKyKDBwMUCg{txO MmLVNlM1PDN6MEW=
HEC155 NE\VWlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXxTWM2OD1yLk[2JOKyKDBwMEmg{txO MnzJNlM1PDN6MEW=
MFE296 M1vpVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfsNnAyUUN3ME2wMlY3KMLzIECuNVkh|ryP MYOyN|Q1OzhyNR?=
SPAC1S MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnWxTWM2OD1yLke3JOKyKDBwMEig{txO MYeyN|Q1OzhyNR?=
RL952 NWS0UJgyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{PnNWlEPTB;MD65N{DDuSByLkCxJO69VQ>? NWjPbFdEOjN2NEO4NFU>
EN1 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjjfmVGUUN3ME2xMlAzKMLzIECuNlUh|ryP Mk\LNlM1PDN6MEW=
SNGII MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTFwMkSgxtEhOC5{ODFOwG0> MlTjNlM1PDN6MEW=
ISHIKAWA MnHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUPJR|UxRTFwM{CgxtEhOC5zMTFOwG0> NVq0RXE1OjN2NEO4NFU>
HEC1A NVjIPJZWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlXrTWM2OD1zLkO0JOKyKDBwM{Cg{txO M4LHRlI{PDR|OEC1
KLE MmHMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUGzXmg3UUN3ME2xMlM4KMLzIECuNFIh|ryP NVq1dY5JOjN2NEO4NFU>
SNGM NHX1[IlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYDCfpNwUUN3ME2xMlQzKMLzIECuNVMh|ryP MljCNlM1PDN6MEW=
USPC2 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYGyXHRVUUN3ME2xMlYzKMLzIECuNFEh|ryP NX;ZcYJYOjN2NEO4NFU>
EN NWjN[5Z2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlXGTWM2OD1zLk[2JOKyKDBwMEGg{txO NI\aWYgzOzR2M{iwOS=>
MFE319 MkHHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTFwOEegxtEhOC52NTFOwG0> MoPsNlM1PDN6MEW=
EFE184 NY[1Npp4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTJwMESgxtEhOC5zMzFOwG0> MUOyN|Q1OzhyNR?=
ECC1 NED6T3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF7Z[JpKSzVyPUKuNFchyrFiMD6wNUDPxE1? MlHBNlM1PDN6MEW=
HEC1B MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGm2VIlKSzVyPUKuOVchyrFiMD6yN{DPxE1? NIT5V4IzOzR2M{iwOS=>
USPC1 NUHZeotOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1y5bGlEPTB;Mj62NEDDuSByLkGzJO69VQ>? M3Pwe|I{PDR|OEC1
SPAC1L NUjOWoNxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2XUU2lEPTB;Mz6wOkDDuSBzLkG0JO69VQ>? MUWyN|Q1OzhyNR?=
HUVEC MYnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1j5flAuOjVizszN NFP6bYg4OiCq NYLCc3BHTE2VTx?= NIToRlJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NHWxT3gzOzJ{OECxOy=>
HMVEC NEGzc4xE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NWDJfXhvOC1{NTFOwG0> M2f4N|czKGh? NXfiSVZ2TE2VTx?= M3\yRYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz Ml;1NlMzOjhyMUe=
MHCC-97H NFvRS2dE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NUO5[48zOC1{NTFOwG0> MkXWO|IhcA>? NYHCclZpTE2VTx?= MlXabY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MUSyN|IzQDBzNx?=
SMMC7721 NIfLN5FE\WyuIG\pZYJqdGm2eTDBd5NigQ>? Ml:0NE0zPSEQvF2= NIfxW2M4OiCq NF:0NpBFVVOR MWHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M{npcVI{OjJ6MEG3
Huh-7 MnjCRZBweHSxc3nzJGF{e2G7 NInnd2IxNTF{LkWg{txO NUnCd|dkOjRiaB?= MXfEUXNQyqB? NYDkVXdZe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? MWWyNlI{ODR5OR?=
Sk-Hep1 NYDCe|VnSXCxcITvd4l{KEG|c3H5 NV7wTYNIOC1zMj61JO69VQ>? NHy4cGozPCCq NFW1XmlFVVORwrC= MXnz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M2e0NVIzOjNyNEe5
Hep3B M2DQVGFxd3C2b4Ppd{BCe3OjeR?= M3rvc|AuOTJwNTFOwG0> MoXSNlQhcA>? MlPrSG1UV8Li NH;VT4F{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz M2X4Z|IzOjNyNEe5
PLC5 NVXkOZVYSXCxcITvd4l{KEG|c3H5 MmnjNE0yOi53IN88US=> MWSyOEBp MmPsSG1UV8Li NGnZ[ph{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz M1vweFIzOjNyNEe5
PLC5 M2TY[mNmdGxiVnnhZoltcXS7IFHzd4F6 MUCwMVE2KM7:TR?= NXmyNFhCPzJiaB?= NXXMcWhFemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg M1HhdlIzOThyM{C4
Hep3B MY\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MYewMVE2KM7:TR?= NW[yNVk2PzJiaB?= MljydoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MlPMNlIyQDB|MEi=
Sk-Hep1 MYnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MoT6NE0yPSEQvF2= MnTZO|IhcA>? MVLy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MnmyNlIyQDB|MEi=
Huh-7 MXnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NUTjZ2ZTOC1zNTFOwG0> MXW3NkBp MWny[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? Mn7QNlIyQDB|MEi=
PLC5 NYfJVmE6SXCxcITvd4l{KEG|c3H5 NWmxOVhLOC1zNTFOwG0> NWD0[W9WOjRiaB?= M4jPWolv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NYHG[ldzOjJzOECzNFg>
Hep3B NYnyWZdESXCxcITvd4l{KEG|c3H5 MVKwMVE2KM7:TR?= M3nXOVI1KGh? NFrnV|RqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NVqwOVV7OjJzOECzNFg>
Sk-Hep1 NUThPWczSXCxcITvd4l{KEG|c3H5 NFXHOHkxNTF3IN88US=> Moj5NlQhcA>? MV\pcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? NXLS[W5mOjJzOECzNFg>
Huh-7 MmfURZBweHSxc3nzJGF{e2G7 MnW2NE0yPSEQvF2= NHH6ZZMzPCCq NU\TV5ZNcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= M3;j[FIzOThyM{C4
PLC5 MmfKSpVv[3Srb36gRZN{[Xl? NGDLTJcxNTFyIN88US=> NY\5ZldzOjRiaB?= M2rreYNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? NY\wUXA5OjJzOECzNFg>
Hep3B MXTGeY5kfGmxbjDBd5NigQ>? MmXxNE0yOCEQvF2= NVrySWRHOjRiaB?= NIn3bYdk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? MXqyNlE5ODNyOB?=
Sk-Hep1 NF31PJhHfW6ldHnvckBCe3OjeR?= NIexRXoxNTFyIN88US=> M3XzNVI1KGh? MXrjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> M4G1bFIzOThyM{C4
Huh-7 M{DW[2Z2dmO2aX;uJGF{e2G7 NYDaR3BWOC1zMDFOwG0> NGrlUmszPCCq NIDnVHBk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NInlW|QzOjF6MEOwPC=>
SW780 NITLNHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY\xbpduPSCm MVPJR|UxRTVyIH7N NYjXNm57OjFzMUm2OlE>
RT112 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTJOUBl M3PnO2lEPTB;MUWgcm0> NG[wVFQzOTFzOU[2NS=>
RT4 MlnpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlvMOUBl MUDJR|UxRTVibl2= NVXR[2tLOjFzMUm2OlE>
JMSU1 NWPSNIduT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHLuTIo2KGR? M17HZ2lEPTB;NUCgcm0> M1:wd|IyOTF7Nk[x
J82 M3frWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX61JIQ> NGLDclJKSzVyPUG0NFAhdk1? M4r0NlIyOTF7Nk[x
97-7 NXftVVNtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkHROUBl MXTJR|UxRTFyMECgcm0> NHvrRnEzOTFzOU[2NS=>
RT112 NYHTT20zTnWwY4Tpc44hSXO|YYm= NEKwO|c2ODBibl2= MmjkNlQhcA>? MknHbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NGPrcWozOTFzOU[2NS=>
RT4 NWDMPJNpTnWwY4Tpc44hSXO|YYm= MUe1NFAhdk1? MX2yOEBp NV\0cmFFcW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz MoLXNlEyOTl4NkG=
MGH-U3 Ml:1SpVv[3Srb36gRZN{[Xl? NHWzXHI2ODBibl2= M3y2VFI1KGh? NGPscXBqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= NHrMZ3YzOTFzOU[2NS=>
SW780 M1j0VGZ2dmO2aX;uJGF{e2G7 M3ezZVUxOCCwTR?= M3PETVI1KGh? MoDlbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NHT4elAzOTFzOU[2NS=>
97-7 MmPVSpVv[3Srb36gRZN{[Xl? MnPvOVAxKG6P NYmxSYYzOjRiaB?= MXnpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? MojONlEyOTl4NkG=
 J807C M{TRRWNmdGxiVnnhZoltcXS7IFHzd4F6 M{e3cVAuPDByIH7N MnywOFghcA>? MlvhbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MnrRNVU2QTh6MUS=
Y373C MmPmR4VtdCCYaXHibYxqfHliQYPzZZk> NULjcnIxOC12MECgcm0> MUi0PEBp M1P2XIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NULGTXE6OTV3OUi4NVQ>
K650E MoTaR4VtdCCYaXHibYxqfHliQYPzZZk> NYixV3loOC12MECgcm0> NXrIeoc5PDhiaB?= Mn3zbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M1jsPVE2PTl6OEG0
G384D M{nmXWNmdGxiVnnhZoltcXS7IFHzd4F6 NF\KXGkxNTRyMDDuUS=> NGjSdok1QCCq NFPTS4NqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NUWwbVFnOTV3OUi4NVQ>
F384L MnHLR4VtdCCYaXHibYxqfHliQYPzZZk> MX[wMVQxOCCwTR?= MYm0PEBp M{fRRYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MUSxOVU6QDhzNB?=
KMS11 NHjFV3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1HqWlczKGh? NF\TO25KSzVyPUmwJI5O MmG2NVU2QTh6MUS=
KMS18 MmTlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;2OmNGPzJiaB?= M2TOS2lEPTB;NUWwJI5O MYGxOVU6QDhzNB?=
OPM2 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWi3NkBp MYPJR|UxRTlyIH7N Ml\sNVU2QTh6MUS=
H929 MonKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlj4O|IhcA>? M37mSWlEPTB-IEK1NFAhdk1? MkS5NVU2QTh6MUS=
8226 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\vS3RHPzJiaB?= NIfJVGhKSzVyPjCyOVAxKG6P MV2xOVU6QDhzNB?=
U266 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{KzZ|czKGh? M32zWGlEPTB-IEK1NFAhdk1? Mli2NVU2QTh6MUS=

... 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 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
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
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

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