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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Cited by 9 Publications

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 NFPLUGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3j2U2lEPTB;MD60OFkh|ryP NWfF[HZDOjV{MEKwO|M>
SupB15-R Mn;CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2HKc2lEPTB;MD61OVgh|ryP NIHa[mMzPTJyMkC3Ny=>
BaF3-pSRα NVHYbZpnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfXeolKSzVyPUCuOlY5KM7:TR?= NU\2WHV5OjV{MEKwO|M>
BaF3-p210Bcr-Abl M1:1N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4rwcmlEPTB;MD62PVIh|ryP NUDjOFk6OjV{MEKwO|M>
BaF3-p210Bcr-Abl-T315I M{LOWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4r2XWlEPTB;Mj62NlYh|ryP MoHoNlUzODJyN{O=
CCRF-CEM M1rBT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTBwM{m4JO69VQ>? MljXNlUzODJyN{K=
CEM/C2 NFXNUldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmW1TWM2OD1zLkGyOUDPxE1? M4r0cVI2OjB{MEey
Nalm-6 NXPXXY17T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;D[VhKSzVyPUCuN|gzKM7:TR?= M{nDWFI2OjB{MEey
SEM-K2 NE\POXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmLvTWM2OD1yLkCyNkDPxE1? NFv2VoQzPTJyMkC3Ni=>
HB-1119 Mly2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVOzUW1OUUN3ME2wMlAzQCEQvF2= NX\QO4RrOjV{MEKwO|I>
RS4:11 M4nLSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH7aOZlKSzVyPUKuPFEh|ryP MX:yOVIxOjB5Mh?=
Nalm-6 Mkn5RZBweHSxc3nzJGF{e2G7 M2iwc|Ih|ryP Ml70NlQwPDhiaB?= M33zfIlv\HWlZYOgZZBweHSxc3nzJJJme3WudHnu[{BqdiCjYn;1eEA4OiVib3[gZ4VtdCCmZXH0bEBi\nSncjCyOEBpKHS{ZXH0cYVvfCCjbnSgPFEmKGGodHXyJFQ5KGh? NI\tbZAzPTJyMkC3Ni=>
SEM-K2 NGDVR5JCeG:ydH;zbZMhSXO|YYm= NVTi[Gc4OC5zL{Gg{txO MkfuNlQhcA>? MUXpcoR2[2W|IHXhdox6KGGyb4D0c5NqeyCxZjDTSW0uUzJiY3XscJMh[XRiMD6xJO69VSCjZoTldkAzPCCq MVGyOVIxOjB5Mh?=
HCT-116 MnOxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MorhTWM2OD1|LkC1NE42QCEQvF2= MoDFNlQ1QTV5NUC=
HT-29 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFi2VmNKSzVyPUWuNlEvQTNizszN NXi2SYd3OjR2OUW3OVA>
SW-480 NWrQ[|I3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIfrR3JKSzVyPUSuN|MxNjR5IN88US=> NWTnblNCOjR2OUW3OVA>
CaCO2 M{O2bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TSeGlEPTB;Mz6yN|AvPjRizszN M3rtV|I1PDl3N{Ww
LS174T Mn31S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fp[mlEPTB;ND6zN|AvPDdizszN NYrUXm5OOjR2OUW3OVA>
HEC-1A NV3Bc5JFTnWwY4Tpc44hSXO|YYm= NHzyeYkxNjB3L{CuNU8xNjVizszN MYi3NkBp NHzNZ5Fk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? NYLIVo1ROjR2OUW3OVA>
AN3CA MVzGeY5kfGmxbjDBd5NigQ>? MWmwMlA2NzBwMT:wMlUh|ryP M4nqVlczKGh? NWDQZ|NJ[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? NXz0dXlrOjR2OUW3OVA>
MFE-296  NV;jV3J5TnWwY4Tpc44hSXO|YYm= NUDhdWh5OC5yNT:wMlEwOC53IN88US=> NFjCcXE4OiCq NGPkd5lk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? MWKyOFQ6PTd3MB?=
UMC3 NFfVT2ZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M{TpfVEuOTBizszN MUC3NkBp NGrSPXpqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MWKyOFMzPTR4MR?=
5637 NHjkd5NE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NV:4cJJYOS1zMDFOwG0> MVK3NkBp M2\PVYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MXiyOFMzPTR4MR?=
HU456 MYLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MmflNU0yOCEQvF2= NGDCVJY4OiCq Mm\LbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MnW1NlQ{OjV2NkG=
MGHU4 NIrkbolE\WyuIG\pZYJqdGm2eTDBd5NigQ>? Mnu3NU0yOCEQvF2= MX63NkBp M1THZYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NVvtN4RXOjR|MkW0OlE>
HT1376 NF3ldJNE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NHrmR|MyNTFyIN88US=> NVPvc3BLPzJiaB?= NYDYN2tjcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MX6yOFMzPTR4MR?=
RT112 M2TxWWNmdGxiVnnhZoltcXS7IFHzd4F6 NUjnS2g1OS1zMDFOwG0> MXy3NkBp NUfjZ5ZmcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MnfLNlQ{OjV2NkG=
T24 MUjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3rYOFEuOTBizszN M17oVFczKGh? NYL0SYVkcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MlTSNlQ{OjV2NkG=
BFTC905 M3LZW2NmdGxiVnnhZoltcXS7IFHzd4F6 NHLEdnoyNTFyIN88US=> NVGzflhNPzJiaB?= MVzpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NX34dGVxOjR|MkW0OlE>
TCC-SUP MX\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NVXCcnRXOS1zMDFOwG0> NFL2UWs4OiCq NX3relVEcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MXGyOFMzPTR4MR?=
RT4 MVPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M{PsOFEuOTBizszN MnPOO|IhcA>? MUHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M4\SOlI1OzJ3NE[x
HONE1 MkT2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTMbmoxNjFvMUCg{txO M4fYd|Q5yqCq M1vRO4lv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NGXl[YozPDJ|OEC5OC=>
HNE1 M1P3b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUGwMlEuOTBizszN MnLEOFjDqGh? MkX6bY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy M3H3blI1OjN6MEm0
CNE2  MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1G0NFAvOS1zMDFOwG0> MWK0POKhcA>? M2PkNYlv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> M{f4dFI1OjN6MEm0
C666-1 NHfhVppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2\2NlAvOS1zMDFOwG0> M1vxblQ5yqCq M33Efolv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> NFLtV3MzPDJ|OEC5OC=>
HeLa Mkm1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIPD[WkxNjFvMUCg{txO NHzXVo4zPCCq MVrpcoR2[2W|IFeyM20h[XK{ZYP0JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy M17LelI1OjN6MEm0
Hep3B NEHnZnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUWwMlEuOTBizszN NGTTWmMzPCCq NWHiZ29PcW6mdXPld{BIOsLiYYLy[ZN1yqB? NFLJSnUzPDJ|OEC5OC=>
HepG2 M{TqdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlvKOFghcA>? MlTFTWM2OD1{LkeyO{DDuSByLkSyPUDPxE1? NXja[HNTOjN3NE[1PVE>
Hep3B MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7ISVN1PDhiaB?= M{nw[WlEPTB;ND6yNlMhyrFiMD64N|kh|ryP M3rI[|I{PTR4NUmx
PLC/PRF5 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXm1XWlwPDhiaB?= M{HucWlEPTB;MU[uNVIxKMLzIESuNFAyKM7:TR?= NFK2PJgzOzV2NkW5NS=>
Huh7 NUnGPY9GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2flblQ5KGh? NFLtRWVKSzVyPUG1MlAxPyEEsTC3MlM{PCEQvF2= MmLWNlM2PDZ3OUG=
HepG2 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYm3NkBp MkH4TWM2OD1zLkKwNEDDuSByLkKyOkDPxE1? NEjwbY0zOzV2NkW5NS=>
Hep3B M3XYXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUWxU|lzPzJiaB?= M37We2lEPTB;MD64PVIhyrFiMD6wOFQh|ryP NU\mVFd5OjN3NE[1PVE>
PLC/PRF5 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXu3NkBp NVj0XZFRUUN3ME2zMlEyOCEEsTCwMlM{PyEQvF2= M1OwZ|I{PTR4NUmx
Huh7 M{TSdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYjEcnF7PzJiaB?= Mkn4TWM2OD1|Lkm4NEDDuSByLkiwN{DPxE1? MVyyN|U1PjV7MR?=
MFE280 NFexRVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUXJR|UxRTBwNEKgxtEhOC5yNjFOwG0> NHHTSnYzOzR2M{iwOS=>
AN3CA M4jTNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XUOGlEPTB;MD61NEDDuSByLkGwJO69VQ>? M1PzRVI{PDR|OEC1
HEC155 MlrxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFrLTJlKSzVyPUCuOlYhyrFiMD6wPUDPxE1? M2TZeVI{PDR|OEC1
MFE296 NHjBNnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXjJR|UxRTBwNk[gxtEhOC5zOTFOwG0> M2LDR|I{PDR|OEC1
SPAC1S MlzpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M37rdWlEPTB;MD63O{DDuSByLkC4JO69VQ>? MYeyN|Q1OzhyNR?=
RL952 NX;yTVNoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXP1VpJqUUN3ME2wMlk{KMLzIECuNFEh|ryP NGPuRVYzOzR2M{iwOS=>
EN1 NHXqeG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWrJR|UxRTFwMEKgxtEhOC5{NTFOwG0> MmDxNlM1PDN6MEW=
SNGII MkLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NU\TPXlYUUN3ME2xMlI1KMLzIECuNlgh|ryP NGnnPIkzOzR2M{iwOS=>
ISHIKAWA M1P2UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYnkV3hiUUN3ME2xMlMxKMLzIECuNVEh|ryP M4TaOlI{PDR|OEC1
HEC1A NXXmZ4xnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3nTd2lEPTB;MT6zOEDDuSByLkOwJO69VQ>? M3\jUFI{PDR|OEC1
KLE MlvaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTFwM{egxtEhOC5yMjFOwG0> M2e2fFI{PDR|OEC1
SNGM MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYLtZ3piUUN3ME2xMlQzKMLzIECuNVMh|ryP NETyd4czOzR2M{iwOS=>
USPC2 NE\tPVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIPtO4VKSzVyPUGuOlIhyrFiMD6wNUDPxE1? M3zQe|I{PDR|OEC1
EN MoXGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGX1clFKSzVyPUGuOlYhyrFiMD6wNUDPxE1? NHfDfnUzOzR2M{iwOS=>
MFE319 NXHZdItQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWTJR|UxRTFwOEegxtEhOC52NTFOwG0> M{O3blI{PDR|OEC1
EFE184 MnzvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDqR3JiUUN3ME2yMlA1KMLzIECuNVMh|ryP Mn7WNlM1PDN6MEW=
ECC1 M2KwOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTJwMEegxtEhOC5yMTFOwG0> MnXsNlM1PDN6MEW=
HEC1B M4TyNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmHZTWM2OD1{LkW3JOKyKDBwMkOg{txO Mn\DNlM1PDN6MEW=
USPC1 NXr6ZWcxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHCWFZSUUN3ME2yMlYxKMLzIECuNVMh|ryP M1XFclI{PDR|OEC1
SPAC1L NEjIOm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYDJR|UxRTNwME[gxtEhOS5zNDFOwG0> NVvTPJBTOjN2NEO4NFU>
HUVEC M2X5dmNmdGxiVnnhZoltcXS7IFHzd4F6 MkWwNE0zPSEQvF2= NEPtbZE4OiCq MXzEUXNQ NV7uSodYcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MoDlNlMzOjhyMUe=
HMVEC MmjGR4VtdCCYaXHibYxqfHliQYPzZZk> NXLsXYRNOC1{NTFOwG0> NXXCNodPPzJiaB?= M1jQWWROW09? NXixTpJ1cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NYDWNlJ6OjN{MkiwNVc>
MHCC-97H MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1nxW|AuOjVizszN MlXLO|IhcA>? M{\FeWROW09? NWe3W41qcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MUGyN|IzQDBzNx?=
SMMC7721 MXjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MVKwMVI2KM7:TR?= MofmO|IhcA>? NYj2bJF2TE2VTx?= M{HPZolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MWmyN|IzQDBzNx?=
Huh-7 NEe2ZZhCeG:ydH;zbZMhSXO|YYm= MlyzNE0yOi53IN88US=> MVeyOEBp M3zNOmROW00EoB?= MWrz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M{LZfVIzOjNyNEe5
Sk-Hep1 NUSxbJN5SXCxcITvd4l{KEG|c3H5 Mn7tNE0yOi53IN88US=> NYn0V48{OjRiaB?= M3L4SmROW00EoB?= M2PjfpNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NIfkOIszOjJ|MES3PS=>
Hep3B NEjJ[5dCeG:ydH;zbZMhSXO|YYm= MlzyNE0yOi53IN88US=> NHPYXpczPCCq MVjEUXNQyqB? NXvPNGNve2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? Ml;qNlIzOzB2N{m=
PLC5 M{foVmFxd3C2b4Ppd{BCe3OjeR?= NWjKc|JvOC1zMj61JO69VQ>? MUeyOEBp NIDLOlJFVVORwrC= M1jX[5NmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> M1LtOFIzOjNyNEe5
PLC5 MonHR4VtdCCYaXHibYxqfHliQYPzZZk> NVG1cJF2OC1zNTFOwG0> NUe4cXB4PzJiaB?= NFToU|Zz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NFvTdIozOjF6MEOwPC=>
Hep3B MV3D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NFLWRWUxNTF3IN88US=> NWq1bnc2PzJiaB?= NG\EdGpz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= M1TZb|IzOThyM{C4
Sk-Hep1 NYLjeoQ1S2WubDDWbYFjcWyrdImgRZN{[Xl? MVywMVE2KM7:TR?= M{fOeFczKGh? NVTWfJNOemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg M4DuR|IzOThyM{C4
Huh-7 NXvyeVVbS2WubDDWbYFjcWyrdImgRZN{[Xl? M2nKSVAuOTVizszN MUm3NkBp NFXG[G1z\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= M1;v[lIzOThyM{C4
PLC5 NGXVbHVCeG:ydH;zbZMhSXO|YYm= M1fwc|AuOTVizszN MUCyOEBp M4f4dYlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M{LzeFIzOThyM{C4
Hep3B NH7x[mZCeG:ydH;zbZMhSXO|YYm= MXiwMVE2KM7:TR?= MWKyOEBp M1LiZolv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M{HMfFIzOThyM{C4
Sk-Hep1 NV70NpJpSXCxcITvd4l{KEG|c3H5 M3jRVlAuOTVizszN M4HMe|I1KGh? MlrvbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NV3JS2gxOjJzOECzNFg>
Huh-7 M4G3cWFxd3C2b4Ppd{BCe3OjeR?= MWKwMVE2KM7:TR?= NVjUeGw2OjRiaB?= MmLmbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MoXaNlIyQDB|MEi=
PLC5 NEPxWmFHfW6ldHnvckBCe3OjeR?= M4nNWFAuOTBizszN MnXINlQhcA>? M1XLcoNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? MXuyNlE5ODNyOB?=
Hep3B MnjSSpVv[3Srb36gRZN{[Xl? M1zve|AuOTBizszN NVfsT2tkOjRiaB?= NUL2V2ts[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w M2f6TFIzOThyM{C4
Sk-Hep1 M1zwW2Z2dmO2aX;uJGF{e2G7 MonzNE0yOCEQvF2= MUGyOEBp NFXDOmVk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NVe3WpdiOjJzOECzNFg>
Huh-7 M{LKNWZ2dmO2aX;uJGF{e2G7 MXiwMVExKM7:TR?= NFTlWZczPCCq NF\Jc3Vk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? M{CzSVIzOThyM{C4
SW780 Mo[3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYC1JIQ> M{P1eGlEPTB;NUCgcm0> Mm\NNlEyOTl4NkG=
RT112 NXO0U5llT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFHmNWg2KGR? MonLTWM2OD1zNTDuUS=> M1jndFIyOTF7Nk[x
RT4 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1n0d|Uh\A>? NI\EXlFKSzVyPUWgcm0> MlfDNlEyOTl4NkG=
JMSU1 MkPWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF\K[Xk2KGR? NVfacmpRUUN3ME21NEBvVQ>? NVzP[nVNOjFzMUm2OlE>
J82 M1HaSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M33wXlUh\A>? NW\jPHpGUUN3ME2xOFAxKG6P NFr6WoszOTFzOU[2NS=>
97-7 NV7oS4FNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13WW|Uh\A>? M4qxUmlEPTB;MUCwNEBvVQ>? NIrpU4gzOTFzOU[2NS=>
RT112 NV;4fFNGTnWwY4Tpc44hSXO|YYm= NHzoOW42ODBibl2= MVKyOEBp NX33NYlIcW6lcnXhd4V{KHSqZTDwdo9xd3K2aX;uJI9nKGOnbHzzJIlvKEdzwrDhZ4NwdXCjbnnl[EBjgSCjIHTlZ5Jm[XOnIHnuJHMh[W6mIFeyM20heGijc3Xz NHn1NmszOTFzOU[2NS=>
RT4 NFPEcmlHfW6ldHnvckBCe3OjeR?= M2jKZVUxOCCwTR?= M3nkfFI1KGh? MX7pcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? Mm\nNlEyOTl4NkG=
MGH-U3 MWrGeY5kfGmxbjDBd5NigQ>? M{\qOlUxOCCwTR?= MmLXNlQhcA>? NFfzNWtqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MYKyNVEyQTZ4MR?=
SW780 NGm2eVhHfW6ldHnvckBCe3OjeR?= NVzvR4JqPTByIH7N NUfYTYtkOjRiaB?= MVjpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? MXGyNVEyQTZ4MR?=
97-7 NH7YVWRHfW6ldHnvckBCe3OjeR?= MYC1NFAhdk1? NFm2PVYzPCCq MlXobY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NIPhTnczOTFzOU[2NS=>
 J807C NGW4UI5E\WyuIG\pZYJqdGm2eTDBd5NigQ>? MnKyNE01ODBibl2= NWPqdnlIPDhiaB?= NXnpcZZGcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NUfDdHI1OTV3OUi4NVQ>
Y373C MUHD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4ryblAuPDByIH7N MWS0PEBp MoPJbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NVXr[lVJOTV3OUi4NVQ>
K650E MlHaR4VtdCCYaXHibYxqfHliQYPzZZk> M{HtbVAuPDByIH7N M2fHVlQ5KGh? NX7PT2RScW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M13xVlE2PTl6OEG0
G384D MVfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3\j[|AuPDByIH7N NHPLUFg1QCCq NVrH[JlNcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M3;yXFE2PTl6OEG0
F384L MV;D[YxtKF[rYXLpcIl1gSCDc4PhfS=> MX[wMVQxOCCwTR?= MUm0PEBp NGm3RVhqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NVPCXpFvOTV3OUi4NVQ>
KMS11 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUi3NkBp NGjjcnpKSzVyPUmwJI5O MXKxOVU6QDhzNB?=
KMS18 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVS3NkBp NX3TNG8{UUN3ME21OVAhdk1? M17MblE2PTl6OEG0
OPM2 MmTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTBR2p7PzJiaB?= NXjIc|lGUUN3ME25NEBvVQ>? MY[xOVU6QDhzNB?=
H929 NYPadmpPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnH6O|IhcA>? MWLJR|UxRiB{NUCwJI5O NWe5bXdlOTV3OUi4NVQ>
8226 M1HKVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnGxO|IhcA>? NUCxS4JUUUN3ME6gNlUxOCCwTR?= MVKxOVU6QDhzNB?=
U266 M2W4NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M37zb|czKGh? M{fRNGlEPTB-IEK1NFAhdk1? M4r3XVE2PTl6OEG0

... 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
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
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
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.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID