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 13 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 M2TNS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXfJR|UxRTBwNES5JO69VQ>? M3XXV|I2OjB{MEez
SupB15-R NVLWUlJRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX7JR|UxRTBwNUW4JO69VQ>? M2rJO|I2OjB{MEez
BaF3-pSRα NXzYTms3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MonGTWM2OD1yLk[2PEDPxE1? M3PBRVI2OjB{MEez
BaF3-p210Bcr-Abl MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIn3SJBKSzVyPUCuOlkzKM7:TR?= M3vQdlI2OjB{MEez
BaF3-p210Bcr-Abl-T315I M{\CSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWrue5lUUUN3ME2yMlYzPiEQvF2= NIrKd3MzPTJyMkC3Ny=>
CCRF-CEM M4Pt[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHrMc4dKSzVyPUCuN|k5KM7:TR?= MkPTNlUzODJyN{K=
CEM/C2 NH;aOYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTFwMUK1JO69VQ>? M{e5U|I2OjB{MEey
Nalm-6 MojFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVPtRnNLUUN3ME2wMlM5OiEQvF2= M17jZVI2OjB{MEey
SEM-K2 M{np[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVzJR|UxRTBwMEKyJO69VQ>? NHvBZVgzPTJyMkC3Ni=>
HB-1119 Mk\pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7tOIxKSzVyPUCuNFI5KM7:TR?= NWLiNG1rOjV{MEKwO|I>
RS4:11 NWLDVXVJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXfJR|UxRTJwOEGg{txO MUWyOVIxOjB5Mh?=
Nalm-6 M4Ps[WFxd3C2b4Ppd{BCe3OjeR?= M4TyNlIh|ryP Mmi3NlQwPDhiaB?= M{j1OYlv\HWlZYOgZZBweHSxc3nzJJJme3WudHnu[{BqdiCjYn;1eEA4OiVib3[gZ4VtdCCmZXH0bEBi\nSncjCyOEBpKHS{ZXH0cYVvfCCjbnSgPFEmKGGodHXyJFQ5KGh? MojzNlUzODJyN{K=
SEM-K2 MVvBdI9xfG:|aYOgRZN{[Xl? MY[wMlEwOSEQvF2= NGjrS2gzPCCq Mn3TbY5lfWOnczDlZZJtgSCjcH;weI9{cXNib3[gV2VONUt{IHPlcIx{KGG2IECuNUDPxE1iYX\0[ZIhOjRiaB?= M4\5O|I2OjB{MEey
HCT-116 NEK2U3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYTJR|UxRTNwMEWwMlU5KM7:TR?= MnTtNlQ1QTV5NUC=
HT-29 NGfp[5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYLWS4pMUUN3ME21MlIyNjl|IN88US=> M17TT|I1PDl3N{Ww
SW-480 M4jNfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTRwM{OwMlQ4KM7:TR?= NGnlV3MzPDR7NUe1NC=>
CaCO2 Mn7JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXf3cXM1UUN3ME2zMlI{OC54NDFOwG0> NV\qdmFjOjR2OUW3OVA>
LS174T Mom5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVnJR|UxRTRwM{OwMlQ4KM7:TR?= MXiyOFQ6PTd3MB?=
HEC-1A MoDaSpVv[3Srb36gRZN{[Xl? NIL1fpAxNjB3L{CuNU8xNjVizszN NF73Voo4OiCq M2\SZYNifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v MYOyOFQ6PTd3MB?=
AN3CA NIq2enVHfW6ldHnvckBCe3OjeR?= MXuwMlA2NzBwMT:wMlUh|ryP MkHYO|IhcA>? M3\yToNifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v NI\EW3UzPDR7NUe1NC=>
MFE-296  NGnENVlHfW6ldHnvckBCe3OjeR?= MkTMNE4xPS9yLkGvNE42KM7:TR?= M3;sTFczKGh? NGXzZZFk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? NEK3VpozPDR7NUe1NC=>
UMC3 MVTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MoTCNU0yOCEQvF2= NGDHRnk4OiCq MV\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MmHvNlQ{OjV2NkG=
5637 NUDN[JhQS2WubDDWbYFjcWyrdImgRZN{[Xl? NWXSOmttOS1zMDFOwG0> NYqzOndlPzJiaB?= MmDtbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MXKyOFMzPTR4MR?=
HU456 MVjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NYrDUFJ1OS1zMDFOwG0> M1zJPVczKGh? M1jFNIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MmPHNlQ{OjV2NkG=
MGHU4 NFfNb3BE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MorTNU0yOCEQvF2= NHjNdnk4OiCq NFXHPY5qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NFXrRWwzPDN{NUS2NS=>
HT1376 NFrlc3ZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M{\uSVEuOTBizszN NIXUOXU4OiCq MUXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MVOyOFMzPTR4MR?=
RT112 Mny0R4VtdCCYaXHibYxqfHliQYPzZZk> Mmr5NU0yOCEQvF2= MkPlO|IhcA>? MXPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M3\GSlI1OzJ3NE[x
T24 MljDR4VtdCCYaXHibYxqfHliQYPzZZk> NHz2O|kyNTFyIN88US=> NEfwNVc4OiCq NFzqNnBqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MWKyOFMzPTR4MR?=
BFTC905 M33vUmNmdGxiVnnhZoltcXS7IFHzd4F6 MUmxMVExKM7:TR?= NEHIfHQ4OiCq MWLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NXnNSWpqOjR|MkW0OlE>
TCC-SUP Mln5R4VtdCCYaXHibYxqfHliQYPzZZk> MYGxMVExKM7:TR?= M2D2SVczKGh? MkPmbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M3j5TFI1OzJ3NE[x
RT4 NIHPV2dE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MlLyNU0yOCEQvF2= M2P0cVczKGh? M2e4W4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MnrRNlQ{OjV2NkG=
HONE1 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFHn[JYxNjFvMUCg{txO MX20POKhcA>? MYTpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= NIfCT5czPDJ|OEC5OC=>
HNE1 NVvpXYE6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXH1OJAxOC5zLUGwJO69VQ>? Ml\5OFjDqGh? NVfQdmtkcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MnTnNlQzOzhyOUS=
CNE2  MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzoWZZ2OC5zLUGwJO69VQ>? NUHW[mdyPDkEoHi= MmXEbY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy MmfPNlQzOzhyOUS=
C666-1 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13zUFAvOS1zMDFOwG0> NG\nXIM1QMLiaB?= Mli1bY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy MoLXNlQzOzhyOUS=
HeLa MlrWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MViwMlEuOTBizszN NIjuSoIzPCCq MUHpcoR2[2W|IFeyM20h[XK{ZYP0JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy NWLlb2htOjR{M{iwPVQ>
Hep3B Mmf3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PqRVAvOS1zMDFOwG0> MmfwNlQhcA>? NY\We5JJcW6mdXPld{BIOsLiYYLy[ZN1yqB? M4S1d|I1OjN6MEm0
HepG2 NEK4[YdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX20PEBp NVzF[mJ3UUN3ME2yMlczPyEEsTCwMlQzQSEQvF2= NGnD[FUzOzV2NkW5NS=>
Hep3B MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUS0PEBp M{LSOGlEPTB;ND6yNlMhyrFiMD64N|kh|ryP MknUNlM2PDZ3OUG=
PLC/PRF5 Mn;3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLB[2J5PDhiaB?= NFjPVFJKSzVyPUG2MlEzOCEEsTC0MlAxOSEQvF2= NWSyNHExOjN3NE[1PVE>
Huh7 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUS3Wm1uPDhiaB?= NEDFc|RKSzVyPUG1MlAxPyEEsTC3MlM{PCEQvF2= NIexWZgzOzV2NkW5NS=>
HepG2 NGTLb3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzOO|IhcA>? MXfJR|UxRTFwMkCwJOKyKDBwMkK2JO69VQ>? MkK5NlM2PDZ3OUG=
Hep3B MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LzeFczKGh? MlzyTWM2OD1yLki5NkDDuSByLkC0OEDPxE1? MmnZNlM2PDZ3OUG=
PLC/PRF5 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{flOFczKGh? MnvTTWM2OD1|LkGxNEDDuSByLkOzO{DPxE1? Ml7vNlM2PDZ3OUG=
Huh7 M4LrSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFTUfYo4OiCq MmfFTWM2OD1|Lkm4NEDDuSByLkiwN{DPxE1? MXOyN|U1PjV7MR?=
MFE280 MnnjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGS1[mhKSzVyPUCuOFIhyrFiMD6wOkDPxE1? NVvVcXZzOjN2NEO4NFU>
AN3CA MmPVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIjj[4VKSzVyPUCuOVAhyrFiMD6xNEDPxE1? NV;jdmhGOjN2NEO4NFU>
HEC155 MkTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnzCTWM2OD1yLk[2JOKyKDBwMEmg{txO NVr6dGhkOjN2NEO4NFU>
MFE296 NGG2Z4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHsT2dKSzVyPUCuOlYhyrFiMD6xPUDPxE1? MnXWNlM1PDN6MEW=
SPAC1S NHHRfmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVrJR|UxRTBwN{egxtEhOC5yODFOwG0> M3PlbVI{PDR|OEC1
RL952 NIC4XZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXSTWM2OD1yLkmzJOKyKDBwMEGg{txO MnzoNlM1PDN6MEW=
EN1 NFrYdIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1i3V2lEPTB;MT6wNkDDuSByLkK1JO69VQ>? NUTyOJJQOjN2NEO4NFU>
SNGII MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYq1SJNwUUN3ME2xMlI1KMLzIECuNlgh|ryP M{LBflI{PDR|OEC1
ISHIKAWA MlrMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{f6UGlEPTB;MT6zNEDDuSByLkGxJO69VQ>? NVnhNG5POjN2NEO4NFU>
HEC1A MoPpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF;MNZlKSzVyPUGuN|QhyrFiMD6zNEDPxE1? MViyN|Q1OzhyNR?=
KLE M2nsOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkHqTWM2OD1zLkO3JOKyKDBwMEKg{txO MVGyN|Q1OzhyNR?=
SNGM MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFPRZWVKSzVyPUGuOFIhyrFiMD6xN{DPxE1? M1LMd|I{PDR|OEC1
USPC2 NY\ZUHBtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vRT2lEPTB;MT62NkDDuSByLkCxJO69VQ>? M4[3N|I{PDR|OEC1
EN NWDSRYlDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfCeYV3UUN3ME2xMlY3KMLzIECuNFEh|ryP MV2yN|Q1OzhyNR?=
MFE319 NH\5XGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYPuTWM{UUN3ME2xMlg4KMLzIECuOFUh|ryP NFvlVo4zOzR2M{iwOS=>
EFE184 Mk[3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE\uWoNKSzVyPUKuNFQhyrFiMD6xN{DPxE1? MXuyN|Q1OzhyNR?=
ECC1 Mor0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYrvdWVPUUN3ME2yMlA4KMLzIECuNFEh|ryP NWj1SWx3OjN2NEO4NFU>
HEC1B MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnjzTWM2OD1{LkW3JOKyKDBwMkOg{txO NV7lcnZzOjN2NEO4NFU>
USPC1 NXvsOnZxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFrrbHFKSzVyPUKuOlAhyrFiMD6xN{DPxE1? NWfycWx1OjN2NEO4NFU>
SPAC1L MlvtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF;aclZKSzVyPUOuNFYhyrFiMT6xOEDPxE1? M4PnblI{PDR|OEC1
HUVEC NYX3c|ROS2WubDDWbYFjcWyrdImgRZN{[Xl? MlrQNE0zPSEQvF2= MlLhO|IhcA>? MkDTSG1UVw>? NGPoXGFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MmT6NlMzOjhyMUe=
HMVEC NYG0WI03S2WubDDWbYFjcWyrdImgRZN{[Xl? MlnjNE0zPSEQvF2= NFnhNJM4OiCq NF7mbWFFVVOR NWm5RpNwcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MmjyNlMzOjhyMUe=
MHCC-97H M1\Ob2NmdGxiVnnhZoltcXS7IFHzd4F6 NH\oO3kxNTJ3IN88US=> NIfpdmU4OiCq Moq3SG1UVw>? MmXWbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NH;IZWYzOzJ{OECxOy=>
SMMC7721 MkXpR4VtdCCYaXHibYxqfHliQYPzZZk> NEnmNJUxNTJ3IN88US=> M364U|czKGh? MUTEUXNQ M2mwUIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NWfaR2VzOjN{MkiwNVc>
Huh-7 MWPBdI9xfG:|aYOgRZN{[Xl? NVP5botuOC1zMj61JO69VQ>? M4PJdlI1KGh? MlW1SG1UV8Li NVK3SYNje2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NH7lNXkzOjJ|MES3PS=>
Sk-Hep1 NYL4THoxSXCxcITvd4l{KEG|c3H5 NFzzfVIxNTF{LkWg{txO MUWyOEBp NIHjOItFVVORwrC= MYrz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M1LkcFIzOjNyNEe5
Hep3B MmHxRZBweHSxc3nzJGF{e2G7 MWewMVEzNjVizszN MX[yOEBp NW\SclFpTE2VT9Mg Mn3nd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> MmnoNlIzOzB2N{m=
PLC5 M4eyOGFxd3C2b4Ppd{BCe3OjeR?= Mkf6NE0yOi53IN88US=> NWHLfodYOjRiaB?= MoL6SG1UV8Li NWm4[HA{e2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NInneGkzOjJ|MES3PS=>
PLC5 M{Wwd2NmdGxiVnnhZoltcXS7IFHzd4F6 NUi5d3k4OC1zNTFOwG0> MniyO|IhcA>? M2W3c5Jm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MnTRNlIyQDB|MEi=
Hep3B NWm0UnRGS2WubDDWbYFjcWyrdImgRZN{[Xl? NU\ZSlYyOC1zNTFOwG0> NXjJb5dZPzJiaB?= NFSydnBz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NXXlW|c4OjJzOECzNFg>
Sk-Hep1 NYi5bohoS2WubDDWbYFjcWyrdImgRZN{[Xl? NUTQN4drOC1zNTFOwG0> MUW3NkBp M3\Vb5Jm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NFLLWGszOjF6MEOwPC=>
Huh-7 MX7D[YxtKF[rYXLpcIl1gSCDc4PhfS=> M2LhbVAuOTVizszN NEnVelQ4OiCq MVLy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NXPOV4ZTOjJzOECzNFg>
PLC5 M3\nbGFxd3C2b4Ppd{BCe3OjeR?= MXOwMVE2KM7:TR?= NYWyS3JVOjRiaB?= MYXpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? M2X2TFIzOThyM{C4
Hep3B Ml3BRZBweHSxc3nzJGF{e2G7 NGrLZpYxNTF3IN88US=> MVuyOEBp M3;x[4lv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M1PPfFIzOThyM{C4
Sk-Hep1 MWXBdI9xfG:|aYOgRZN{[Xl? MV2wMVE2KM7:TR?= M13Se|I1KGh? MULpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? Mm\VNlIyQDB|MEi=
Huh-7 MXnBdI9xfG:|aYOgRZN{[Xl? MYWwMVE2KM7:TR?= MnjsNlQhcA>? NYXCb4txcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NGPhd5MzOjF6MEOwPC=>
PLC5 M3TqPGZ2dmO2aX;uJGF{e2G7 NEHCWpQxNTFyIN88US=> M4myOlI1KGh? NHnYToFk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NYnDb5J2OjJzOECzNFg>
Hep3B M4jVWGZ2dmO2aX;uJGF{e2G7 M2jNdFAuOTBizszN NF[3SI0zPCCq NHXPb4hk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? MX:yNlE5ODNyOB?=
Sk-Hep1 MYrGeY5kfGmxbjDBd5NigQ>? MX[wMVExKM7:TR?= M1LhdVI1KGh? MnnnZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v MWqyNlE5ODNyOB?=
Huh-7 NVLBb4NITnWwY4Tpc44hSXO|YYm= M4j0UFAuOTBizszN M3nKNVI1KGh? MlW0Z4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v NWXQfWwzOjJzOECzNFg>
SW780 M1KyN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4S5cVUh\A>? M{DMeWlEPTB;NUCgcm0> NXXBNmRyOjFzMUm2OlE>
RT112 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYKxUVZHPSCm MWTJR|UxRTF3IH7N MU[yNVEyQTZ4MR?=
RT4 NVX5fG06T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWK1JIQ> NY\RRmN7UUN3ME21JI5O Mnv3NlEyOTl4NkG=
JMSU1 NWezb5VJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4T6UFUh\A>? NXe4TVFKUUN3ME21NEBvVQ>? MoPGNlEyOTl4NkG=
J82 MnPyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{\6cFUh\A>? NULmO3FkUUN3ME2xOFAxKG6P NX;H[m1yOjFzMUm2OlE>
97-7 M370Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2XRc|Uh\A>? Mo\GTWM2OD1zMECwJI5O MmfCNlEyOTl4NkG=
RT112 NHuyb2FHfW6ldHnvckBCe3OjeR?= M{[1ZVUxOCCwTR?= NWfnSJpMOjRiaB?= NHLod|ZqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= NIrqPHAzOTFzOU[2NS=>
RT4 MmLlSpVv[3Srb36gRZN{[Xl? Mo\oOVAxKG6P MVKyOEBp NHr5bFFqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MUWyNVEyQTZ4MR?=
MGH-U3 MoTvSpVv[3Srb36gRZN{[Xl? NFr4dY42ODBibl2= Mo\TNlQhcA>? NIfnPJNqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= M3T0WlIyOTF7Nk[x
SW780 M4HXRWZ2dmO2aX;uJGF{e2G7 MkLEOVAxKG6P M3rST|I1KGh? MVfpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NH;wd4UzOTFzOU[2NS=>
97-7 M2D0ZmZ2dmO2aX;uJGF{e2G7 NF7TXYY2ODBibl2= MXuyOEBp M4PoSolv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= NWH0UXpnOjFzMUm2OlE>
 J807C MULD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4\Zb|AuPDByIH7N M1Lz[lQ5KGh? MmXObY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NFz2NZkyPTV7OEixOC=>
Y373C MlvIR4VtdCCYaXHibYxqfHliQYPzZZk> M13Hb|AuPDByIH7N MkL4OFghcA>? NIO1XYJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NIe0SJoyPTV7OEixOC=>
K650E NHntW3FE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NGrxT2ExNTRyMDDuUS=> Mn\rOFghcA>? M{XWOolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MVuxOVU6QDhzNB?=
G384D MX7D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NX30RnNLOC12MECgcm0> NV;OS2VkPDhiaB?= M17xPYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NHjXOVYyPTV7OEixOC=>
F384L MnfsR4VtdCCYaXHibYxqfHliQYPzZZk> MV:wMVQxOCCwTR?= NFThbFQ1QCCq NVf0RoRScW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NGnpXmIyPTV7OEixOC=>
KMS11 NF71VJVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPBO|IhcA>? M4TmWWlEPTB;OUCgcm0> MVixOVU6QDhzNB?=
KMS18 M4H0b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUS3NkBp NH7QXYNKSzVyPUW1NEBvVQ>? MVGxOVU6QDhzNB?=
OPM2 NEn1Oo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF;aPHc4OiCq MnzuTWM2OD17MDDuUS=> NUPuOYJlOTV3OUi4NVQ>
H929 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUe3NkBp NEnyfHpKSzVyPjCyOVAxKG6P NUn1R2JjOTV3OUi4NVQ>
8226 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;5T|czKGh? MWDJR|UxRiB{NUCwJI5O MnTSNVU2QTh6MUS=
U266 M1yxZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3z4[lczKGh? MYnJR|UxRiB{NUCwJI5O NILvR2IyPTV7OEixOC=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
CDK1 / p-CDK1 / p53 / p21 ; 

PubMed: 24238094     


(A) Dovitinib induces phosphorylation of CDK1(Tyr15) in nasopharyngeal carcinoma cells. HONE1 cells were incubated with Dovitinib (5 μM) and harvested at the indicated time-points. Lysates were prepared and the indicated proteins were detected with immunoblotting. Equal loading of lysates was confirmed by immunoblotting for actin. (B) Dovitinib induces phosphorylation of CDK1Tyr15 in HeLa cells. HeLa cells were exposed to the indicated concentrations of Dovitinib for 24 hrs. Lysates were prepared and analysed with immunoblotting. Equal loading of extracts was accessed by immunoblotting of actin. (C) Dovitinib induces phosphorylation of CDK1Tyr15 in Hep3B cells. Hep3B cells were treated with the indicated concentrations of Dovitinib for 24 hrs. Lysates were prepared for immunoblotting analysis. Actin was probed to confirm equal loading. 

p-PDGFR-β / PDGFR-β / p-ERK / ERK ; 

PubMed: 23228017     


Phosphorylation of p-PDGFR-β and p-ERK were inhibited by dovitinib at pharmacologically relevant concentrations in MHCC-97H and SMMC7721 cells.

p-VEGFR-2 / VEGFR-2 / p-FGFR-1 / FGFR-1 ; 

PubMed: 23228017     


Dovitinib inhibited the phosphorylation of FGFG-1, VEGFR-2, and downstream ERK in HMVEC and HUVEC endothelial cells at pharmacologically relevant concentrations.

p-STAT3 / STAT3 / Mcl-1 / LC3 / Beclin 1 / p62 ; 

PubMed: 31485222     


The protein extracts from dovitinib-treated were subjected to immunoblot analysis for p-STAT3, STAT3, Mcl-1, beclin1, LC3B, p62, and actin.

24238094 23228017 31485222
Growth inhibition assay
Cell viability; 

PubMed: 28467797     


Cell viability of peripheral blood mononuclear cells (PBMCs) and RPMI8226 cells treated with dovitinib in RPMI1640 medium containing 5% FBS for 24 h. Data are presented as mean±SD. Experiments were performed in triplicate.* P < 0.01, **P < 0.001 versus control.

28467797
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]
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  • 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 interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02268435 Withdrawn Drug: dovitinib plus imatinib Gastrointestinal Stromal Tumors Asan Medical Center March 2015 Phase 1
NCT01700270 Completed Drug: dovitinib (TKI258)|Drug: fluvoxamine Advanced Solid Tumors Excluding Breast Cancer Novartis Pharmaceuticals|Novartis May 2013 Phase 1
NCT01680796 Withdrawn Drug: Dovitinib|Drug: Bortezomib|Drug: Dexamethasone Multiple Myeloma University of Florida|Novartis Pharmaceuticals February 2013 Phase 1
NCT01266070 Terminated Drug: Dovitinib Von Hippel-Lindau Syndrome M.D. Anderson Cancer Center|Novartis November 2012 Phase 2
NCT01515969 Terminated Drug: Erlotinib hydrochloride|Drug: Dovitinib lactate Non-small Cell Lung Cancer (NSCLC) Recurrent|Non-small Cell Lung Cancer (NSCLC) Stage IV Heather Wakelee|Genentech Inc.|Novartis|Stanford University July 2012 Phase 1
NCT01030055 Completed Drug: TKI258 (dovitinib) Neoplasms|Cancer|Tumors Novartis Pharmaceuticals|Novartis February 2010 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID