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 10 Publications

7 Customer Reviews

  •  

    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.

    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.

  • 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.

    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.

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 MmrBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjkS3JKSzVyPUCuOFQ6KM7:TR?= M4\NUVI2OjB{MEez
SupB15-R NXXtbXQ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn3PTWM2OD1yLkW1PEDPxE1? NEHPfY0zPTJyMkC3Ny=>
BaF3-pSRα M4PIcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlvQTWM2OD1yLk[2PEDPxE1? MYOyOVIxOjB5Mx?=
BaF3-p210Bcr-Abl MlTNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVjJR|UxRTBwNkmyJO69VQ>? M4nKcFI2OjB{MEez
BaF3-p210Bcr-Abl-T315I NH7BXohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXfJR|UxRTJwNkK2JO69VQ>? M2TMPVI2OjB{MEez
CCRF-CEM M4DQV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7QTWM2OD1yLkO5PEDPxE1? MX2yOVIxOjB5Mh?=
CEM/C2 NU\3O2V1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXhXYZUUUN3ME2xMlEzPSEQvF2= NGTxUlIzPTJyMkC3Ni=>
Nalm-6 M{fFW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLNWY5QUUN3ME2wMlM5OiEQvF2= MnHFNlUzODJyN{K=
SEM-K2 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHqb3F7UUN3ME2wMlAzOiEQvF2= M4jnb|I2OjB{MEey
HB-1119 NY\NUVhTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3ezOWlEPTB;MD6wNlgh|ryP MnHoNlUzODJyN{K=
RS4:11 MlvvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2nDcWlEPTB;Mj64NUDPxE1? NU\WS2FSOjV{MEKwO|I>
Nalm-6 MoXvRZBweHSxc3nzJGF{e2G7 NWXaZoM3OiEQvF2= NWXON5RlOjRxNEigbC=> MVPpcoR2[2W|IHHwc5B1d3OrczDy[ZN2dHSrbnegbY4h[WKxdYSgO|ImKG:oIHPlcIwh\GWjdHigZYZ1\XJiMkSgbEB1emWjdH3lcpQh[W6mIEixKUBi\nSncjC0PEBp MYqyOVIxOjB5Mh?=
SEM-K2 NVOzdFJYSXCxcITvd4l{KEG|c3H5 NWLud2xoOC5zL{Gg{txO NX3PcI5MOjRiaB?= NEnvU4JqdmS3Y3XzJIViemy7IHHwc5B1d3OrczDv[kBUTU1vS{KgZ4VtdHNiYYSgNE4yKM7:TTDh[pRmeiB{NDDo NYjHNWdMOjV{MEKwO|I>
HCT-116 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1e3ZmlEPTB;Mz6wOVAvPThizszN NXyxSlNnOjR2OUW3OVA>
HT-29 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEC1SYRKSzVyPUWuNlEvQTNizszN NW\HXJhDOjR2OUW3OVA>
SW-480 NFPkeGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoXFTWM2OD12LkOzNE41PyEQvF2= NUHkOFZVOjR2OUW3OVA>
CaCO2 MnX5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{Xxb2lEPTB;Mz6yN|AvPjRizszN MVKyOFQ6PTd3MB?=
LS174T MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXrPe4ZkUUN3ME20MlM{OC52NzFOwG0> NYPmdWZ4OjR2OUW3OVA>
HEC-1A NV;3NFQ6TnWwY4Tpc44hSXO|YYm= MlfBNE4xPS9yLkGvNE42KM7:TR?= NUfUeVJpPzJiaB?= M2i1ZoNifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v MknUNlQ1QTV5NUC=
AN3CA MYnGeY5kfGmxbjDBd5NigQ>? NUm1NoZ{OC5yNT:wMlEwOC53IN88US=> MXu3NkBp MmTUZ4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> MnnxNlQ1QTV5NUC=
MFE-296  MoraSpVv[3Srb36gRZN{[Xl? MmjhNE4xPS9yLkGvNE42KM7:TR?= MoKzO|IhcA>? MUnjZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> M4mxPFI1PDl3N{Ww
UMC3 NUfnXFBGS2WubDDWbYFjcWyrdImgRZN{[Xl? MlrWNU0yOCEQvF2= NEjzVmI4OiCq NHW1blNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M3TXelI1OzJ3NE[x
5637 Mn7nR4VtdCCYaXHibYxqfHliQYPzZZk> MXWxMVExKM7:TR?= Ml7lO|IhcA>? M3zNeYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MX:yOFMzPTR4MR?=
HU456 M{m1ZmNmdGxiVnnhZoltcXS7IFHzd4F6 NULldFJLOS1zMDFOwG0> MWO3NkBp NEHxbnRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M4raXVI1OzJ3NE[x
MGHU4 NGjiTHZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MU[xMVExKM7:TR?= NH;MNFE4OiCq NGPTRXJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MYeyOFMzPTR4MR?=
HT1376 Mlj3R4VtdCCYaXHibYxqfHliQYPzZZk> NFTaW5IyNTFyIN88US=> MoLvO|IhcA>? NF\hdoZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NXzKd2tKOjR|MkW0OlE>
RT112 MmDOR4VtdCCYaXHibYxqfHliQYPzZZk> MoHPNU0yOCEQvF2= Ml\RO|IhcA>? M2O3XIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MWiyOFMzPTR4MR?=
T24 MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MlyyNU0yOCEQvF2= NXXOU3N2PzJiaB?= NX\udYQ2cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M3rrflI1OzJ3NE[x
BFTC905 NWXqRVlbS2WubDDWbYFjcWyrdImgRZN{[Xl? NVv5eolUOS1zMDFOwG0> MV[3NkBp MoH4bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MmLBNlQ{OjV2NkG=
TCC-SUP NWS5V2Z[S2WubDDWbYFjcWyrdImgRZN{[Xl? MVKxMVExKM7:TR?= NXL0[JZbPzJiaB?= M{XnUolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M4DTelI1OzJ3NE[x
RT4 MY\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NU\GUoJPOS1zMDFOwG0> NW\ISYFtPzJiaB?= NGKyTXpqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MWKyOFMzPTR4MR?=
HONE1 M1TmbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXrPclFuOC5zLUGwJO69VQ>? M1LYe|Q5yqCq NHLvPWpqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NUKzV3lYOjR{M{iwPVQ>
HNE1 NXXXRnh5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfYNE4yNTFyIN88US=> MWW0POKhcA>? NYnZXYxXcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MXWyOFI{QDB7NB?=
CNE2  NVP5SVh3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWD2UmlFOC5zLUGwJO69VQ>? M3excVQ5yqCq M3LoUolv\HWlZYOgS|IwVSCmZXzhfUBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> M2PvZlI1OjN6MEm0
C666-1 M4LKWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX[wMlEuOTBizszN NXrEdGY{PDkEoHi= NF7nd5dqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NI\FPJIzPDJ|OEC5OC=>
HeLa MkTnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGTCUmwxNjFvMUCg{txO NU\0SlF7OjRiaB?= NF3GbW5qdmS3Y3XzJGczN01iYYLy[ZN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M2n5NVI1OjN6MEm0
Hep3B MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXiwMlEuOTBizszN M17LU|I1KGh? Ml;hbY5lfWOnczDHNuKh[XK{ZYP0xsA> MlfONlQzOzhyOUS=
HepG2 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYO0PEBp MW\JR|UxRTJwN{K3JOKyKDBwNEK5JO69VQ>? MUSyN|U1PjV7MR?=
Hep3B M1Llemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETUZXg1QCCq NWL5XnBvUUN3ME20MlIzOyEEsTCwMlg{QSEQvF2= NEnIVXMzOzV2NkW5NS=>
PLC/PRF5 NYH1U2ZHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1W1d|Q5KGh? NWTD[WNNUUN3ME2xOk4yOjBiwsGgOE4xODFizszN MmWxNlM2PDZ3OUG=
Huh7 NELjdJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPZSII1QCCq M3HXbmlEPTB;MUWuNFA4KMLzIEeuN|M1KM7:TR?= M3HNXFI{PTR4NUmx
HepG2 NGL4OWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mki5O|IhcA>? MlfoTWM2OD1zLkKwNEDDuSByLkKyOkDPxE1? NGr2TXIzOzV2NkW5NS=>
Hep3B MmHWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml20O|IhcA>? NGH1c3lKSzVyPUCuPFkzKMLzIECuNFQ1KM7:TR?= M3TKVlI{PTR4NUmx
PLC/PRF5 M37rXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWm3NkBp M1HsbWlEPTB;Mz6xNVAhyrFiMD6zN|ch|ryP NFv0V2gzOzV2NkW5NS=>
Huh7 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mle4O|IhcA>? M2fUPGlEPTB;Mz65PFAhyrFiMD64NFMh|ryP MYiyN|U1PjV7MR?=
MFE280 NETUcopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\VSoFKSzVyPUCuOFIhyrFiMD6wOkDPxE1? NEfyV|gzOzR2M{iwOS=>
AN3CA NHniNoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF[3SodKSzVyPUCuOVAhyrFiMD6xNEDPxE1? M17NSFI{PDR|OEC1
HEC155 NGDoOphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;LTWlEPTB;MD62OkDDuSByLkC5JO69VQ>? M37kZlI{PDR|OEC1
MFE296 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWfRVHJUUUN3ME2wMlY3KMLzIECuNVkh|ryP MnKxNlM1PDN6MEW=
SPAC1S NY\PfWhqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUnJR|UxRTBwN{egxtEhOC5yODFOwG0> MojRNlM1PDN6MEW=
RL952 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoT1TWM2OD1yLkmzJOKyKDBwMEGg{txO M1LwelI{PDR|OEC1
EN1 NHrkb5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGnzTGVKSzVyPUGuNFIhyrFiMD6yOUDPxE1? NUnjc456OjN2NEO4NFU>
SNGII NVHRV5hVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXLJR|UxRTFwMkSgxtEhOC5{ODFOwG0> MYKyN|Q1OzhyNR?=
ISHIKAWA MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1rwNWlEPTB;MT6zNEDDuSByLkGxJO69VQ>? NYTGXIY{OjN2NEO4NFU>
HEC1A NYr1dJpTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3P2RWlEPTB;MT6zOEDDuSByLkOwJO69VQ>? NEOyNnYzOzR2M{iwOS=>
KLE MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml\rTWM2OD1zLkO3JOKyKDBwMEKg{txO MlrlNlM1PDN6MEW=
SNGM NWDaNVJnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYPJR|UxRTFwNEKgxtEhOC5zMzFOwG0> NFPMOnYzOzR2M{iwOS=>
USPC2 NUf3[mlsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUW0fIR3UUN3ME2xMlYzKMLzIECuNFEh|ryP M1jmOlI{PDR|OEC1
EN MlX0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrPNYdTUUN3ME2xMlY3KMLzIECuNFEh|ryP M1zIbVI{PDR|OEC1
MFE319 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWnJR|UxRTFwOEegxtEhOC52NTFOwG0> NH;mNIIzOzR2M{iwOS=>
EFE184 NVXycm9qT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MU\JR|UxRTJwMESgxtEhOC5zMzFOwG0> NE\jdVczOzR2M{iwOS=>
ECC1 NWXHUIdDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlj5TWM2OD1{LkC3JOKyKDBwMEGg{txO NIDjbY8zOzR2M{iwOS=>
HEC1B NXHEO4Y2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFTV[YFKSzVyPUKuOVchyrFiMD6yN{DPxE1? M4PVbVI{PDR|OEC1
USPC1 M2fzPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rLbWlEPTB;Mj62NEDDuSByLkGzJO69VQ>? NVvRUYV3OjN2NEO4NFU>
SPAC1L NXO5UFY5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTNwME[gxtEhOS5zNDFOwG0> NXrNXIVzOjN2NEO4NFU>
HUVEC MofqR4VtdCCYaXHibYxqfHliQYPzZZk> M{\oO|AuOjVizszN NXK4ZVNDPzJiaB?= NYPu[FdbTE2VTx?= MmPabY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MWGyN|IzQDBzNx?=
HMVEC NUS0cmxnS2WubDDWbYFjcWyrdImgRZN{[Xl? M3S2c|AuOjVizszN NFPTO4Q4OiCq MWXEUXNQ NF3sOVZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MVeyN|IzQDBzNx?=
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SMMC7721 MXTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NH3iTVkxNTJ3IN88US=> NW\BWoJiPzJiaB?= NYXWZ3VRTE2VTx?= M2\3fIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M{fXXlI{OjJ6MEG3
Huh-7 NYjUe4FESXCxcITvd4l{KEG|c3H5 M{nuRVAuOTJwNTFOwG0> M2L2T|I1KGh? MVzEUXNQyqB? M1;Ic5NmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NVLSc4JnOjJ{M{C0O|k>
Sk-Hep1 Mki3RZBweHSxc3nzJGF{e2G7 MXywMVEzNjVizszN MnTiNlQhcA>? NIPGOlRFVVORwrC= NXzsc5Bwe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? M1izVFIzOjNyNEe5
Hep3B MXPBdI9xfG:|aYOgRZN{[Xl? NF7BWGMxNTF{LkWg{txO NXHYVpM5OjRiaB?= MnrLSG1UV8Li NUTnS5gze2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NH7kVIczOjJ|MES3PS=>
PLC5 NVW1b2NOSXCxcITvd4l{KEG|c3H5 MmfzNE0yOi53IN88US=> M1m0O|I1KGh? MXfEUXNQyqB? NY\6cYVPe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? M3LMWVIzOjNyNEe5
PLC5 M{n6e2NmdGxiVnnhZoltcXS7IFHzd4F6 MV2wMVE2KM7:TR?= NGexcGY4OiCq NYr6XZU2emWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg NWS5dpVJOjJzOECzNFg>
Hep3B MVTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4ft[FAuOTVizszN MVS3NkBp Mo\YdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M2H6WVIzOThyM{C4
Sk-Hep1 MUTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MUmwMVE2KM7:TR?= MoPoO|IhcA>? MXHy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? M1z0XlIzOThyM{C4
Huh-7 MkLmR4VtdCCYaXHibYxqfHliQYPzZZk> NUS4VnB[OC1zNTFOwG0> NXHidFJ7PzJiaB?= M1jCbpJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MmjMNlIyQDB|MEi=
PLC5 Mm[1RZBweHSxc3nzJGF{e2G7 NFHoNY4xNTF3IN88US=> NHLZeFMzPCCq Mmq1bY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MmLkNlIyQDB|MEi=
Hep3B NWT3cXpVSXCxcITvd4l{KEG|c3H5 M2n4NFAuOTVizszN NXf1VZhCOjRiaB?= M{nvRYlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NY\KXmdbOjJzOECzNFg>
Sk-Hep1 NGnqVHNCeG:ydH;zbZMhSXO|YYm= NIS2bYUxNTF3IN88US=> NFLiPHUzPCCq NHLXZWZqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NIjpZ3ozOjF6MEOwPC=>
Huh-7 NEjkU|VCeG:ydH;zbZMhSXO|YYm= M4nrW|AuOTVizszN MkLzNlQhcA>? MnHhbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MoTFNlIyQDB|MEi=
PLC5 MoLUSpVv[3Srb36gRZN{[Xl? NYjwO4xQOC1zMDFOwG0> MUOyOEBp NYrMVXJp[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NXX6NYd3OjJzOECzNFg>
Hep3B MWTGeY5kfGmxbjDBd5NigQ>? NVLYU4lQOC1zMDFOwG0> NXTHSVlFOjRiaB?= NUm3bmxT[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w M3nwflIzOThyM{C4
Sk-Hep1 MmXzSpVv[3Srb36gRZN{[Xl? NXfDWZBuOC1zMDFOwG0> NVfxe29NOjRiaB?= M4PS[oNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? M2fuR|IzOThyM{C4
Huh-7 NWjJbYRMTnWwY4Tpc44hSXO|YYm= NFvyWZcxNTFyIN88US=> NWmyOm1OOjRiaB?= NYDYUGpr[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NFfE[5kzOjF6MEOwPC=>
SW780 Mmm2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUm1JIQ> MlfpTWM2OD13MDDuUS=> MnPvNlEyOTl4NkG=
RT112 NH\od2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPIemE2KGR? MXjJR|UxRTF3IH7N NUP0enJSOjFzMUm2OlE>
RT4 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYC1JIQ> NHG5OJNKSzVyPUWgcm0> NWqzeHEzOjFzMUm2OlE>
JMSU1 M1HDc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3S5O|Uh\A>? Ml3NTWM2OD13MDDuUS=> MYeyNVEyQTZ4MR?=
J82 MoriS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX61JIQ> NHTkZmVKSzVyPUG0NFAhdk1? MoHJNlEyOTl4NkG=
97-7 NV;MOYtRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYS1JIQ> MlPmTWM2OD1zMECwJI5O MXmyNVEyQTZ4MR?=
RT112 MlfnSpVv[3Srb36gRZN{[Xl? MlH3OVAxKG6P NGrMd|YzPCCq MVjpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NYTodVZbOjFzMUm2OlE>
RT4 M3HpPWZ2dmO2aX;uJGF{e2G7 NHryRY02ODBibl2= MYeyOEBp M3[wRolv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= M2LqeVIyOTF7Nk[x
MGH-U3 NH:4PIRHfW6ldHnvckBCe3OjeR?= MUm1NFAhdk1? NX3EOWloOjRiaB?= MoTwbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| MXyyNVEyQTZ4MR?=
SW780 NVnxXZRWTnWwY4Tpc44hSXO|YYm= MmLEOVAxKG6P M2PlUVI1KGh? MVvpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NXu2b4VSOjFzMUm2OlE>
97-7 NGHEU2VHfW6ldHnvckBCe3OjeR?= M3PtNlUxOCCwTR?= Mlm5NlQhcA>? M2TUc4lv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= NE[4RlkzOTFzOU[2NS=>
 J807C NIPjUJlE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NFq1TlIxNTRyMDDuUS=> NWP2OmU4PDhiaB?= MoHhbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MVuxOVU6QDhzNB?=
Y373C M4\Qd2NmdGxiVnnhZoltcXS7IFHzd4F6 NWPQSIFOOC12MECgcm0> NWDrPGVCPDhiaB?= MYnpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M{n0O|E2PTl6OEG0
K650E M{HsUGNmdGxiVnnhZoltcXS7IFHzd4F6 MWOwMVQxOCCwTR?= NHjrRXE1QCCq M3\YeYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MXKxOVU6QDhzNB?=
G384D MVPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MUCwMVQxOCCwTR?= M2D5UlQ5KGh? MorVbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M2XzN|E2PTl6OEG0
F384L NHPhO45E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NWTiXJVVOC12MECgcm0> NWOwempyPDhiaB?= NVmzfG5mcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NG\FO|YyPTV7OEixOC=>
KMS11 NYLwVXNjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfxO|IhcA>? Mly0TWM2OD17MDDuUS=> Mk\3NVU2QTh6MUS=
KMS18 MlLrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1P1XFczKGh? MUfJR|UxRTV3MDDuUS=> NFGxdlEyPTV7OEixOC=>
OPM2 M4PhVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mkj4O|IhcA>? NWXZV5NUUUN3ME25NEBvVQ>? NVHkUmZ6OTV3OUi4NVQ>
H929 M3TIWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoqzO|IhcA>? NFHHWWdKSzVyPjCyOVAxKG6P NEXzbGwyPTV7OEixOC=>
8226 NVOzTIJHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoD1O|IhcA>? NXT3fZA5UUN3ME6gNlUxOCCwTR?= MXKxOVU6QDhzNB?=
U266 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;kZ3lkPzJiaB?= MVPJR|UxRiB{NUCwJI5O NXTBcnB{OTV3OUi4NVQ>

... 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.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID