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 43 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)
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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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HepG2 MlTSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH[xNXA4OiCq NXjJbHZFUUN3ME2xMlIxOCEEsTCwMlIzPiEQvF2= MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV2NkW5NUc,OjN3NE[1PVE9N2F-
Hep3B NV;qUmNXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFXIelk4OiCq NEfaTXJKSzVyPUCuPFkzKMLzIECuNFQ1KM7:TR?= Mn25QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NE[1PVEoRjJ|NUS2OVkyRC:jPh?=
PLC/PRF5 NHHDPGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV[3NkBp NYOySVd6UUN3ME2zMlEyOCEEsTCwMlM{PyEQvF2= MoW5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NE[1PVEoRjJ|NUS2OVkyRC:jPh?=
Huh7 MnPZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4\3OlczKGh? MmPQTWM2OD1|Lkm4NEDDuSByLkiwN{DPxE1? NVLyNmVLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFY2QTFpPkKzOVQ3PTlzPD;hQi=>
MFE280 NW[2N5I6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnjHTWM2OD1yLkSyJOKyKDBwME[g{txO NUWwd|BwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
AN3CA NWjiOGExT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYP4eHBtUUN3ME2wMlUxKMLzIECuNVAh|ryP NWjIVWtxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
HEC155 MnL1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTlZ2NFUUN3ME2wMlY3KMLzIECuNFkh|ryP MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
MFE296 NFLURo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnvwTWM2OD1yLk[2JOKyKDBwMUmg{txO MnrvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
SPAC1S Mn61S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTBwN{egxtEhOC5yODFOwG0> NIXXS2w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
RL952 MkfSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fWe2lEPTB;MD65N{DDuSByLkCxJO69VQ>? MknPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
EN1 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHDSFZuUUN3ME2xMlAzKMLzIECuNlUh|ryP NG\o[Ig9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
SNGII M4DFNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;tdmlEPTB;MT6yOEDDuSByLkK4JO69VQ>? NXXGT|JWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
ISHIKAWA MmC2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTFwM{CgxtEhOC5zMTFOwG0> MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
HEC1A M4nlS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nmVGlEPTB;MT6zOEDDuSByLkOwJO69VQ>? NXzDPWl6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
KLE MkTJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWLJR|UxRTFwM{egxtEhOC5yMjFOwG0> M13qSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
SNGM NELTNFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV3JR|UxRTFwNEKgxtEhOC5zMzFOwG0> MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
USPC2 M4mycmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1\6fmlEPTB;MT62NkDDuSByLkCxJO69VQ>? NXjsUYN2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
EN NInNXmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4PXZ2lEPTB;MT62OkDDuSByLkCxJO69VQ>? NGK0OWY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S0N|gxPSd-MkO0OFM5ODV:L3G+
MFE319 M1;wd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfEeFc{UUN3ME2xMlg4KMLzIECuOFUh|ryP MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
EFE184 NWrPTYV4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXX4fVlIUUN3ME2yMlA1KMLzIECuNVMh|ryP M2fWWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
ECC1 MlfhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXLJR|UxRTJwMEegxtEhOC5yMTFOwG0> MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR2M{iwOUc,OjN2NEO4NFU9N2F-
HEC1B MoPIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTBW5pbUUN3ME2yMlU4KMLzIECuNlMh|ryP NYnwc|c1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0OFM5ODVpPkKzOFQ{QDB3PD;hQi=>
USPC1 NFrySWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1HEZWlEPTB;Mj62NEDDuSByLkGzJO69VQ>? MmXqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2NEO4NFUoRjJ|NESzPFA2RC:jPh?=
SPAC1L MmLQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLETWM2OD1|LkC2JOKyKDFwMUSg{txO M3zXc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NESzPFA2Lz5{M{S0N|gxPTxxYU6=
HUVEC NGr1Xo5E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NGD3NnoxNTJ3IN88US=> NEX0T3I4OiCq M1zvW2ROW09? MoHUbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M3\WfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MkK4NFE4Lz5{M{KyPFAyPzxxYU6=
HMVEC MUjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MV[wMVI2KM7:TR?= M1iwTlczKGh? MVPEUXNQ M{TvOIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz Ml;FQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{MkiwNVcoRjJ|MkK4NFE4RC:jPh?=
MHCC-97H NHvZ[o1E\WyuIG\pZYJqdGm2eTDBd5NigQ>? NIHLSVgxNTJ3IN88US=> MXq3NkBp NYmwZnBjTE2VTx?= NIrVb2lqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Mlu1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{MkiwNVcoRjJ|MkK4NFE4RC:jPh?=
SMMC7721 NV:0TYl4S2WubDDWbYFjcWyrdImgRZN{[Xl? M2fBb|AuOjVizszN NEHPUo44OiCq Mmr3SG1UVw>? NEPvT|hqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ{OECxO{c,OjN{MkiwNVc9N2F-
Huh-7 MV\BdI9xfG:|aYOgRZN{[Xl? NVfMPGc3OC1zMj61JO69VQ>? NXjKcpR{OjRiaB?= M1XhNWROW00EoB?= NYDZNm1ue2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? M{HEUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MkOwOFc6Lz5{MkKzNFQ4QTxxYU6=
Sk-Hep1 NFrMeZRCeG:ydH;zbZMhSXO|YYm= NX\qeGYxOC1zMj61JO69VQ>? M4rBXVI1KGh? MmPQSG1UV8Li M1HyRpNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NIPzXIE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkKzNFQ4QSd-MkKyN|A1Pzl:L3G+
Hep3B MXjBdI9xfG:|aYOgRZN{[Xl? NEXac4oxNTF{LkWg{txO M1niSVI1KGh? MV\EUXNQyqB? M3fmd5NmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ|MES3PUc,OjJ{M{C0O|k9N2F-
PLC5 NXuxN3RpSXCxcITvd4l{KEG|c3H5 M3faNFAuOTJwNTFOwG0> MXGyOEBp Ml3zSG1UV8Li MVLz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ|MES3PUc,OjJ{M{C0O|k9N2F-
PLC5 NYjOfmM{S2WubDDWbYFjcWyrdImgRZN{[Xl? NW\hcW15OC1zNTFOwG0> NU[0UoxvPzJiaB?= NXnRRWFGemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg MnnBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Hep3B NH\NZ3BE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NF7rZpcxNTF3IN88US=> MlHXO|IhcA>? MVry[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NWXDNIhZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxPFA{ODhpPkKyNVgxOzB6PD;hQi=>
Sk-Hep1 NVT6[YxtS2WubDDWbYFjcWyrdImgRZN{[Xl? MlHENE0yPSEQvF2= NUXqZnJuPzJiaB?= NETabGdz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NFPZ[pA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Huh-7 M{DpbmNmdGxiVnnhZoltcXS7IFHzd4F6 MWKwMVE2KM7:TR?= MUW3NkBp NV3R[HVEemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg M{nkVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUiwN|A5Lz5{MkG4NFMxQDxxYU6=
PLC5 NHjIWJVCeG:ydH;zbZMhSXO|YYm= M{jTcFAuOTVizszN MkjxNlQhcA>? NVfOcmZmcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= NXTXZ5hXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxPFA{ODhpPkKyNVgxOzB6PD;hQi=>
Hep3B NHy4XoFCeG:ydH;zbZMhSXO|YYm= NH;ySZoxNTF3IN88US=> M{XMSVI1KGh? NGTkTYRqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= Mk\lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Sk-Hep1 MnXqRZBweHSxc3nzJGF{e2G7 M2XTPFAuOTVizszN NEfwR3UzPCCq MnXIbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? MnPpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Huh-7 NGjCUXhCeG:ydH;zbZMhSXO|YYm= NVnOeIM2OC1zNTFOwG0> NYThN3BMOjRiaB?= NEfIPGJqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= NXTTU|MxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxPFA{ODhpPkKyNVgxOzB6PD;hQi=>
PLC5 MVPGeY5kfGmxbjDBd5NigQ>? NHvFeWwxNTFyIN88US=> MUmyOEBp NHTPVnBk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? M3fWTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUiwN|A5Lz5{MkG4NFMxQDxxYU6=
Hep3B NULV[VBDTnWwY4Tpc44hSXO|YYm= MoH6NE0yOCEQvF2= MX[yOEBp NV7O[FdQ[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NGX6bpk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG4NFMxQCd-MkKxPFA{ODh:L3G+
Sk-Hep1 NFfVVWJHfW6ldHnvckBCe3OjeR?= NH3nTYYxNTFyIN88US=> NXjZbFFHOjRiaB?= M1HqR4NifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? MnLKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzOECzNFgoRjJ{MUiwN|A5RC:jPh?=
Huh-7 MVzGeY5kfGmxbjDBd5NigQ>? NY\uNHhuOC1zMDFOwG0> M{jHUlI1KGh? M3jTTYNifXOnczDkc5NmNWSncHXu[IVvfCCGTlGg[pJi\22nboTheIlwdg>? MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF6MEOwPEc,OjJzOECzNFg9N2F-
SW780 MlW3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVO5XFl{PSCm M3vs[mlEPTB;NUCgcm0> MkLFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzMUm2OlEoRjJzMUG5OlYyRC:jPh?=
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SK-N-SH M2OxbZFJXFNiYYPzZZk> M1mycZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz NFzjSVY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
NB1643 NV7wcm1ZeUiWUzDhd5NigQ>? NFzSW45yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz MoDsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
LAN-5 M3nBcZFJXFNiYYPzZZk> MYfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN? MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
BT-12 NHvY[WFyUFSVIHHzd4F6 MnjTdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy| MoPmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh18 NHyycHFyUFSVIHHzd4F6 NGnNWFByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnixPEBk\Wyucx?= M3q2eVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50 MmLudWhVWyCjc4PhfS=> MYLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy| M1OxelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD NInkeJZyUFSVIHHzd4F6 NYTCfopLeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGLEJINmdGy| NF7STXY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
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NCI-H1703 MXrGeY5kfGmxbjDhd5NigQ>? M4i2PVExKHWP NWjJWmtUOjRiaILz NFrYRo1KdmirYnn0bY9vKG:oIGTOTWshcW5iaIXtZY4hVkOLLVixO|A{KGOnbHzzJJRz[W6|ZnXjeIVlKHerdHigcIVvfGm4aYLhcEB3\WO2b4KgO3RHWCCjc4Pld5Nm\CCjczDy[YR2[3Srb36gc4YhT1ONMzDpcohq[mm2b4KgXEBi[3SrdnH0[YQhXE6LSz3t[YRq[XSnZDDXcpQwXEOIL3LleIEu[2G2ZX7pck1l\XCnbnTlcpQhfHKjboPjdolxfGmxbjDheEAyOCC3TTDh[pRmeiB{NDDodpMh[nlibIXjbYZmemG|ZTDy[ZBwenSncjDhd5NigQ>? NXy5NYZHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTJ{OEmyM{c,S2iHTVLMQE9iRg>?
LoVo M{[2U2N6fG:2b4jpZ4l1gSCjc4PhfS=> NFHSTocyOCC3TR?= MWm3NkBpenN? MlTVR5l1d3SxeHnjbZR6KGGpYXnud5QhX262L3LleIEu[2G2ZX7pckB{cWewYXzsbY5oKGSncHXu[IVvfCCqdX3hckBNd1[xIHPlcIx{KGG|c3Xzd4VlKGG|IHPlcIwhfmmjYnnsbZR6KGG2IEGwJJVOKGGodHXyJFczKGi{czDifUBCXFCuaYTlJIF{e2G7 MmfUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVIzQDl{Lze+R4hGVUKOPD;hQi=>
HCT116 NGf6TXdEgXSxdH;4bYNqfHliYYPzZZk> MWqxNEB2VQ>? NHn4PYM4OiCqcoO= MWfDfZRwfG:6aXPpeJkh[WejaX7zeEBYdnRxYnX0ZU1k[XSnbnnuJJNq\26jbHzpcoch\GWyZX7k[Y51KGi3bXHuJGhEXDFzNjDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjdDCxNEB2VSCjZoTldkA4OiCqcoOgZpkhSVSSbHn0[UBie3OjeR?= NH;Ibos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2OjJ6OUKvK|5EcEWPQly8M4E,
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.
Animal Research:[1]
  • Animal Models: 8-week-old female BNX mice bearing KMS11 cells
  • Dosages: 10, 30, or 60 mg/kg
  • Administration: Gavage

Solubility (25°C)

In vitro

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

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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