Dovitinib (TKI-258)

Catalog No.S1018 Synonyms: CHIR-258

For research use only.

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.

Dovitinib (TKI-258) Chemical Structure

CAS No. 405169-16-6

Selleck's Dovitinib (TKI-258) has been cited by 42 publications

Purity & Quality Control

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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)
Click to View More Targets
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
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BaF3-p210Bcr-Abl Mn3GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYHGZm1[UUN3ME2wMlY6OiEQvF2= MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJyMkC3N{c,OjV{MEKwO|M9N2F-
BaF3-p210Bcr-Abl-T315I NFLaUG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnnrTWM2OD1{Lk[yOkDPxE1? NFm0SY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKwNlA4Oyd-MkWyNFIxPzN:L3G+
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Nalm-6 MoDwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUfJR|UxRTBwM{iyJO69VQ>? MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJyMkC3Nkc,OjV{MEKwO|I9N2F-
SEM-K2 NY\IV|FVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NULKcWtKUUN3ME2wMlAzOiEQvF2= M4DBbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkCyNFczLz5{NUKwNlA4OjxxYU6=
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HT-29 NGe4TIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2PRbmlEPTB;NT6yNU46OyEQvF2= MlHwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OUW3OVAoRjJ2NEm1O|UxRC:jPh?=
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CaCO2 MofLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzm[|NCUUN3ME2zMlI{OC54NDFOwG0> NUTIVoZtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVU4PTBpPkK0OFk2PzVyPD;hQi=>
LS174T M2PqXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTRwM{OwMlQ4KM7:TR?= MkHOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OUW3OVAoRjJ2NEm1O|UxRC:jPh?=
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AN3CA MlL5SpVv[3Srb36gRZN{[Xl? NIOze5AxNjB3L{CuNU8xNjVizszN MmjlO|IhcA>? MmLjZ4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> M4rqTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEm1O|UxLz5{NES5OVc2ODxxYU6=
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Hep3B NGXjVVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEjLWYIxNjFvMUCg{txO M{iyN|I1KGh? M4fud4lv\HWlZYOgS|LDqGG{cnXzeOKh MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ|OEC5OEc,OjR{M{iwPVQ9N2F-
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Huh7 M2XKS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlTQOFghcA>? M2P3emlEPTB;MUWuNFA4KMLzIEeuN|M1KM7:TR?= M1\SO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUS2OVkyLz5{M{W0OlU6OTxxYU6=
HepG2 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3TBeVczKGh? NYrPWYwyUUN3ME2xMlIxOCEEsTCwMlIzPiEQvF2= NYm2WmM6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFY2QTFpPkKzOVQ3PTlzPD;hQi=>
Hep3B NYD3N|JkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4S1SlczKGh? M3nzTmlEPTB;MD64PVIhyrFiMD6wOFQh|ryP NFz6OlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{W0OlU6OSd-MkO1OFY2QTF:L3G+
PLC/PRF5 NFy1co5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGXDbVg4OiCq MW\JR|UxRTNwMUGwJOKyKDBwM{O3JO69VQ>? NYPvWWNlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFY2QTFpPkKzOVQ3PTlzPD;hQi=>
Huh7 NIW4[2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4OwWFczKGh? NGTtVlFKSzVyPUOuPVgxKMLzIECuPFA{KM7:TR?= NWf2XFVoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFY2QTFpPkKzOVQ3PTlzPD;hQi=>
MFE280 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHIbW1FUUN3ME2wMlQzKMLzIECuNFYh|ryP NFjaZWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
AN3CA M2HSN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfCTWM2OD1yLkWwJOKyKDBwMUCg{txO NWTpOHNtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
HEC155 NIXldYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVzJR|UxRTBwNk[gxtEhOC5yOTFOwG0> NHm4N5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
MFE296 NEjJcmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkO1TWM2OD1yLk[2JOKyKDBwMUmg{txO MknQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
SPAC1S NWLabnI5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{nmWmlEPTB;MD63O{DDuSByLkC4JO69VQ>? NIOwZYQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
RL952 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2q4TGlEPTB;MD65N{DDuSByLkCxJO69VQ>? NW[2fWVqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
EN1 NYW1T5FrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2qxbGlEPTB;MT6wNkDDuSByLkK1JO69VQ>? MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
SNGII M1vTcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX3ZdHBjUUN3ME2xMlI1KMLzIECuNlgh|ryP M2XWOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
ISHIKAWA MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIjaXIFKSzVyPUGuN|AhyrFiMD6xNUDPxE1? MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
HEC1A M4XXemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYXLVJNDUUN3ME2xMlM1KMLzIECuN|Ah|ryP MnL5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
KLE M1nweGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{H5U2lEPTB;MT6zO{DDuSByLkCyJO69VQ>? NFvXN|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
SNGM MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXXzS4F{UUN3ME2xMlQzKMLzIECuNVMh|ryP M4P3TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
USPC2 M2\tRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVjJR|UxRTFwNkKgxtEhOC5yMTFOwG0> NF3Pfng9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
EN NEXWTmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPvTWM2OD1zLk[2JOKyKDBwMEGg{txO NX7tZXF5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
MFE319 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTYTWM2OD1zLki3JOKyKDBwNEWg{txO MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
EFE184 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnS0TWM2OD1{LkC0JOKyKDBwMUOg{txO MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
ECC1 NEXpNYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPkZYhTUUN3ME2yMlA4KMLzIECuNFEh|ryP NU\BSo5WRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
HEC1B MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn7hTWM2OD1{LkW3JOKyKDBwMkOg{txO NUnNZ|NPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
USPC1 NVXmWJJpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGj1RnVKSzVyPUKuOlAhyrFiMD6xN{DPxE1? NGfFOGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
SPAC1L NXq1b3VKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnj6TWM2OD1|LkC2JOKyKDFwMUSg{txO NI\JTpk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
HUVEC NVO4Nmt6S2WubDDWbYFjcWyrdImgRZN{[Xl? M3TSNlAuOjVizszN NGn1NIU4OiCq M4TPbWROW09? MmfobY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ{OECxO{c,OjN{MkiwNVc9N2F-
HMVEC MnvqR4VtdCCYaXHibYxqfHliQYPzZZk> NG[wSpcxNTJ3IN88US=> MWS3NkBp MnXJSG1UVw>? NFmyZWdqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MmjPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{MkiwNVcoRjJ|MkK4NFE4RC:jPh?=
MHCC-97H NETJOG5E\WyuIG\pZYJqdGm2eTDBd5NigQ>? M3zXSlAuOjVizszN NX;KflVqPzJiaB?= NGPiOYlFVVOR MlvabY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NUXRVWtURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyNlgxOTdpPkKzNlI5ODF5PD;hQi=>
SMMC7721 MoPMR4VtdCCYaXHibYxqfHliQYPzZZk> MWOwMVI2KM7:TR?= MXq3NkBp M1HNUWROW09? NIDPWG5qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ{OECxO{c,OjN{MkiwNVc9N2F-
Huh-7 M2fES2Fxd3C2b4Ppd{BCe3OjeR?= MoTRNE0yOi53IN88US=> M4LlOVI1KGh? NFzz[25FVVORwrC= M1OzS5NmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NIP2SFk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkKzNFQ4QSd-MkKyN|A1Pzl:L3G+
Sk-Hep1 M3ThfmFxd3C2b4Ppd{BCe3OjeR?= MlPFNE0yOi53IN88US=> NILGZ2IzPCCq MoXGSG1UV8Li MYPz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M4DGcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MkOwOFc6Lz5{MkKzNFQ4QTxxYU6=
Hep3B MmfwRZBweHSxc3nzJGF{e2G7 MknQNE0yOi53IN88US=> NIDyWoQzPCCq NEjPZW5FVVORwrC= MoPsd4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ|MES3PUc,OjJ{M{C0O|k9N2F-
PLC5 M{njfmFxd3C2b4Ppd{BCe3OjeR?= M1S3W|AuOTJwNTFOwG0> NE\ReFgzPCCq MoXtSG1UV8Li NG\rTZJ{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz NEjpWIQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkKzNFQ4QSd-MkKyN|A1Pzl:L3G+
PLC5 M4TKdWNmdGxiVnnhZoltcXS7IFHzd4F6 NWPwVVVyOC1zNTFOwG0> NXPrfllJPzJiaB?= Moe2doVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MoPqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Hep3B NH22c3hE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MWiwMVE2KM7:TR?= Mm[3O|IhcA>? MlnDdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NIC3T5M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Sk-Hep1 NXO5PWpmS2WubDDWbYFjcWyrdImgRZN{[Xl? NX7vdWtLOC1zNTFOwG0> MoPOO|IhcA>? M2fKcpJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NFf4ZXY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Huh-7 NFe5fVdE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M3n2T|AuOTVizszN NXzTcGZGPzJiaB?= NVXZZ5hOemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
PLC5 MUHBdI9xfG:|aYOgRZN{[Xl? NWHacJJZOC1zNTFOwG0> NVO3RY5ZOjRiaB?= NYiyVmM5cW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NIX2eVU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Hep3B NUj0T5FQSXCxcITvd4l{KEG|c3H5 NV7rSFBYOC1zNTFOwG0> NFnWcpEzPCCq NFizUJlqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MlftQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Sk-Hep1 MmjFRZBweHSxc3nzJGF{e2G7 M4f2c|AuOTVizszN NVHycG1POjRiaB?= MVjpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Huh-7 M2n0bmFxd3C2b4Ppd{BCe3OjeR?= NF3DTYIxNTF3IN88US=> MXuyOEBp NV[2U45icW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
PLC5 NWnWUHBsTnWwY4Tpc44hSXO|YYm= M4\RNFAuOTBizszN MkLGNlQhcA>? NWrKZ24y[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NV:5RmpNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxPFA{ODhpPkKyNVgxOzB6PD;hQi=>
Hep3B M4exZmZ2dmO2aX;uJGF{e2G7 MVmwMVExKM7:TR?= MoLxNlQhcA>? NFj2Z3lk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Sk-Hep1 NHLDXpFHfW6ldHnvckBCe3OjeR?= NUSxfJU4OC1zMDFOwG0> MkK0NlQhcA>? MmDrZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
Huh-7 NEjCfodHfW6ldHnvckBCe3OjeR?= MlvHNE0yOCEQvF2= NHjjb5UzPCCq NFPmU4Rk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NFHaZVI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
SW780 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYe1JIQ> MVvJR|UxRTVyIH7N MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTFzOU[2NUc,OjFzMUm2OlE9N2F-
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NB1643 MorWdWhVWyCjc4PhfS=> NXmweIhNeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=> M1PtbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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Rh18 NEmwRXByUFSVIHHzd4F6 NXfYPVJbeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGLoNVgh[2WubIO= M4\JXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50 MXPxTHRUKGG|c3H5 MmjydWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE:KUz21NEBk\Wyucx?= MmfGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
RD NGriXpByUFSVIHHzd4F6 NV:yR5FUeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGLEJINmdGy| MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
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NCI-H1703 Ml\ISpVv[3Srb36gZZN{[Xl? NUD3[2ZQOTBidV2= MXSyOEBpenN? NXj3dFBYUW6qaXLpeIlwdiCxZjDUUmlMKGmwIHj1cYFvKE6FST3INVcxOyClZXzsd{B1emGwc3\lZ5Rm\CC5aYToJIxmdnSrdnnyZYwhfmWldH;yJFdVTlBiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJI9nKEeVS{OgbY5pcWKrdH;yJHgh[WO2aY\heIVlKFSQSVutcYVlcWG2ZXSgW451N1SFRj;i[ZRiNWOjdHXubY4u\GWyZX7k[Y51KHS{YX7zZ5JqeHSrb36gZZQhOTBidV2gZYZ1\XJiMkSgbJJ{KGK7IHz1Z4ln\XKjc3WgdoVxd3K2ZYKgZZN{[Xl? MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1NlI5QTJxJ{7DbGVOSkx:L3G+
LoVo NVHQUXJMS3m2b4TvfIlkcXS7IHHzd4F6 MVGxNEB2VQ>? M3WyWVczKGi{cx?= MXHDfZRwfG:6aXPpeJkh[WejaX7zeEBYdnRxYnX0ZU1k[XSnbnnuJJNq\26jbHzpcoch\GWyZX7k[Y51KGi3bXHuJGxwXm9iY3XscJMh[XO|ZYPz[YQh[XNiY3XscEB3cWGkaXzpeJkh[XRiMUCgeW0h[W[2ZYKgO|IhcHK|IHL5JGFVWGyrdHWgZZN{[Xl? NXfrW2M4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTJ{OEmyM{c,S2iHTVLMQE9iRg>?
HCT116 NGrsblREgXSxdH;4bYNqfHliYYPzZZk> MoWzNVAhfU1? MXq3NkBpenN? MVHDfZRwfG:6aXPpeJkh[WejaX7zeEBYdnRxYnX0ZU1k[XSnbnnuJJNq\26jbHzpcoch\GWyZX7k[Y51KGi3bXHuJGhEXDFzNjDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjdDCxNEB2VSCjZoTldkA4OiCqcoOgZpkhSVSSbHn0[UBie3OjeR?= M4rGflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFUzOjh7Mj:nQmNpTU2ETEyvZV4>
Assay
Methods Test Index PMID
Western blot CDK1 / p-CDK1 / p53 / p21 ; p-PDGFR-β / PDGFR-β / p-ERK / ERK ; p-VEGFR-2 / VEGFR-2 / p-FGFR-1 / FGFR-1 ; p-STAT3 / STAT3 / Mcl-1 / LC3 / Beclin 1 / p62 24238094 23228017 31485222
Growth inhibition assay Cell viability 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 (from reference)

Kinase Assay:[1]
  • 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]
  • 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]
  • Animal Models: 8-week-old female BNX mice bearing KMS11 cells
  • 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 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=C(C5=C(C=CC=C5F)NC4=O)N

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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