Dovitinib (TKI-258, CHIR-258)

Dovitinib (TKI258, CHIR258)は一種の多ターゲットRTK阻害剤で、無細胞試験でIII型(FLT3/c-Kit)に作用する効果が一番強くて、このIC50値が1 nM/2 nMです。同時に、Dovitinib (TKI258, CHIR258)はIV型(FGFR1/3)とV型(VEGFR1-4) RTKsにも有効に作用して、IC50値が8-13 nMになりますが、InsR、EGFR、c-Met、EphA2、Tie2、IGF-1RとHER2に作用する効果が少し弱くなります。臨床4期。

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Dovitinib (TKI-258, CHIR-258) 化学構造
分子量: 392.43

高品質保証

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製品説明

  • Compare FLT3 Inhibitors
    FLT3製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 Dovitinib (TKI258, CHIR258)は一種の多ターゲットRTK阻害剤で、無細胞試験でIII型(FLT3/c-Kit)に作用する効果が一番強くて、このIC50値が1 nM/2 nMです。同時に、Dovitinib (TKI258, CHIR258)はIV型(FGFR1/3)とV型(VEGFR1-4) RTKsにも有効に作用して、IC50値が8-13 nMになりますが、InsR、EGFR、c-Met、EphA2、Tie2、IGF-1RとHER2に作用する効果が少し弱くなります。臨床4期。
ターゲット Flt3 c-Kit FGFR1/3 VEGFR1/2/3 PDGFRα/β
IC50 1 nM 2 nM 8 nM/9 nM 10 nM/13 nM/8 nM 210 nM/27 nM [1]
In vitro試験 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
SupB15 M1S0Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTBwNES5JO69VQ>? NHvHeVIzPTJyMkC3Ny=>
SupB15-R MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWfJR|UxRTBwNUW4JO69VQ>? MlS2NlUzODJyN{O=
BaF3-pSRα Mm\1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW\JR|UxRTBwNk[4JO69VQ>? NF;HOnUzPTJyMkC3Ny=>
BaF3-p210Bcr-Abl MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV3CSFhwUUN3ME2wMlY6OiEQvF2= NHL3O|MzPTJyMkC3Ny=>
BaF3-p210Bcr-Abl-T315I MnHKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXvsXZpCUUN3ME2yMlYzPiEQvF2= MV:yOVIxOjB5Mx?=
CCRF-CEM NGLoXJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml7TTWM2OD1yLkO5PEDPxE1? NYThVoszOjV{MEKwO|I>
CEM/C2 NILNdlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojrTWM2OD1zLkGyOUDPxE1? MWSyOVIxOjB5Mh?=
Nalm-6 NVfJVWZXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHIVlhtUUN3ME2wMlM5OiEQvF2= NIHFSoMzPTJyMkC3Ni=>
SEM-K2 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnOfHRtUUN3ME2wMlAzOiEQvF2= M{n6PVI2OjB{MEey
HB-1119 M3rNe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTBwMEK4JO69VQ>? NULGPFRpOjV{MEKwO|I>
RS4:11 NVfqb4QxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml;ZTWM2OD1{LkixJO69VQ>? MmLQNlUzODJyN{K=
Nalm-6 MX;BdI9xfG:|aYOgRZN{[Xl? MUCyJO69VQ>? MUCyOE81QCCq M1vNWolv\HWlZYOgZZBweHSxc3nzJJJme3WudHnu[{BqdiCjYn;1eEA4OiVib3[gZ4VtdCCmZXH0bEBi\nSncjCyOEBpKHS{ZXH0cYVvfCCjbnSgPFEmKGGodHXyJFQ5KGh? MVSyOVIxOjB5Mh?=
SEM-K2 M3q1fWFxd3C2b4Ppd{BCe3OjeR?= Mn64NE4yNzFizszN MlvjNlQhcA>? MX\pcoR2[2W|IHXhdox6KGGyb4D0c5NqeyCxZjDTSW0uUzJiY3XscJMh[XRiMD6xJO69VSCjZoTldkAzPCCq MlXwNlUzODJyN{K=
HCT-116 NU\uWmxrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnLFTWM2OD1|LkC1NE42QCEQvF2= MmTwNlQ1QTV5NUC=
HT-29 MlzOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHfLOmRKSzVyPUWuNlEvQTNizszN M{ewWVI1PDl3N{Ww
SW-480 NVjDbVIzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\OTWM2OD12LkOzNE41PyEQvF2= M4jYXlI1PDl3N{Ww
CaCO2 M2Tr[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWnETlhlUUN3ME2zMlI{OC54NDFOwG0> NWC5ZpcyOjR2OUW3OVA>
LS174T MmLsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoP3TWM2OD12LkOzNE41PyEQvF2= NFS0OWwzPDR7NUe1NC=>
HEC-1A MX7GeY5kfGmxbjDBd5NigQ>? NHf0N2ExNjB3L{CuNU8xNjVizszN NYS2Z2hPPzJiaB?= MX3jZZV{\XNiYTDk[YNz\WG|ZTDpckBUXEGWMzygSXJMNCCjbnSgRWtVKHCqb4PwbI9zgWyjdHnvci=> M{fBPVI1PDl3N{Ww
AN3CA MXnGeY5kfGmxbjDBd5NigQ>? NVTLd2IxOC5yNT:wMlEwOC53IN88US=> Mk\JO|IhcA>? Mln6Z4F2e2W|IHGg[IVkemWjc3WgbY4hW1SDVEOsJGVTUyxiYX7kJGFMXCCyaH;zdIhwenmuYYTpc44> M4DtWlI1PDl3N{Ww
MFE-296  NEPHNYRHfW6ldHnvckBCe3OjeR?= NGfOS28xNjB3L{CuNU8xNjVizszN MXm3NkBp M2LlV4NifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v NH3jPVkzPDR7NUe1NC=>
UMC3 NV\VOG1yS2WubDDWbYFjcWyrdImgRZN{[Xl? NHyzOGQyNTFyIN88US=> Mn;wO|IhcA>? MnK4bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MXGyOFMzPTR4MR?=
5637 M1HJS2NmdGxiVnnhZoltcXS7IFHzd4F6 M{n3VFEuOTBizszN MkP4O|IhcA>? NWfZcIJMcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NIfSdmczPDN{NUS2NS=>
HU456 NW[1elRUS2WubDDWbYFjcWyrdImgRZN{[Xl? NV3GT2J{OS1zMDFOwG0> M3HtOFczKGh? NIr1W|ZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MXuyOFMzPTR4MR?=
MGHU4 MULD[YxtKF[rYXLpcIl1gSCDc4PhfS=> Ml;INU0yOCEQvF2= MUG3NkBp NYPIRmtucW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MXqyOFMzPTR4MR?=
HT1376 M4[3T2NmdGxiVnnhZoltcXS7IFHzd4F6 MlvpNU0yOCEQvF2= NWO1eoJtPzJiaB?= NFLMVHZqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MkThNlQ{OjV2NkG=
RT112 MnH3R4VtdCCYaXHibYxqfHliQYPzZZk> NEDZVJUyNTFyIN88US=> NGfQVI04OiCq NYHkbnJVcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mo\oNlQ{OjV2NkG=
T24 NFzTR4tE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MWCxMVExKM7:TR?= MUi3NkBp NFTGRnlqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M1;DWFI1OzJ3NE[x
BFTC905 MnuyR4VtdCCYaXHibYxqfHliQYPzZZk> M1[xOVEuOTBizszN NFn6TZA4OiCq NVTkSXBYcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NHrZeJYzPDN{NUS2NS=>
TCC-SUP NYPCUnpzS2WubDDWbYFjcWyrdImgRZN{[Xl? NYDkV5pEOS1zMDFOwG0> NVXaTVdnPzJiaB?= NHziTldqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NGOzVIwzPDN{NUS2NS=>
RT4 M2XUZmNmdGxiVnnhZoltcXS7IFHzd4F6 M1jndlEuOTBizszN M{nLPFczKGh? M4\HUIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MUmyOFMzPTR4MR?=
HONE1 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDkbYkxNjFvMUCg{txO MXK0POKhcA>? MXzpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MV2yOFI{QDB7NB?=
HNE1 MkPaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\tNE4yNTFyIN88US=> NGW2[XY1QMLiaB?= MUXpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= NGrB[mkzPDJ|OEC5OC=>
CNE2  NHHLdllIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPVfZgxNjFvMUCg{txO MUS0POKhcA>? NHz6d4tqdmS3Y3XzJGczN01iZHXsZZkhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> M3jkNFI1OjN6MEm0
C666-1 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYiwMlEuOTBizszN MYm0POKhcA>? NYrOXXBNcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NGLa[FQzPDJ|OEC5OC=>
HeLa MkXqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{m4dlAvOS1zMDFOwG0> MXGyOEBp NUCzfFFFcW6mdXPld{BIOi:PIHHydoV{fCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MW[yOFI{QDB7NB?=
Hep3B MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkPrNE4yNTFyIN88US=> NYPyflZROjRiaB?= NUG2WnN4cW6mdXPld{BIOsLiYYLy[ZN1yqB? Mk\4NlQzOzhyOUS=
HepG2 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3rod|Q5KGh? Ml3ZTWM2OD1{LkeyO{DDuSByLkSyPUDPxE1? MWWyN|U1PjV7MR?=
Hep3B MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2DsNVQ5KGh? NGHieZlKSzVyPUSuNlI{KMLzIECuPFM6KM7:TR?= MkPMNlM2PDZ3OUG=
PLC/PRF5 NYnXb5BxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYi0PEBp MnjTTWM2OD1zNj6xNlAhyrFiND6wNFEh|ryP NWjGdppDOjN3NE[1PVE>
Huh7 NIS4VJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2nSeVQ5KGh? NV61OVZQUUN3ME2xOU4xODdiwsGgO{4{OzRizszN NHzEVWkzOzV2NkW5NS=>
HepG2 MoHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX[3NkBp MXfJR|UxRTFwMkCwJOKyKDBwMkK2JO69VQ>? MXGyN|U1PjV7MR?=
Hep3B M1H4eGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFfVV|k4OiCq NVHTbpNOUUN3ME2wMlg6OiEEsTCwMlA1PCEQvF2= NU\iU3l{OjN3NE[1PVE>
PLC/PRF5 NHTl[YFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIq1NFg4OiCq NHmxclVKSzVyPUOuNVExKMLzIECuN|M4KM7:TR?= MnPDNlM2PDZ3OUG=
Huh7 NWTpRXRXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXu3NkBp NXnIPIt3UUN3ME2zMlk5OCEEsTCwMlgxOyEQvF2= NXL0WnF4OjN3NE[1PVE>
MFE280 M4HZXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUfJR|UxRTBwNEKgxtEhOC5yNjFOwG0> MU[yN|Q1OzhyNR?=
AN3CA NFTwR3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3HGd2lEPTB;MD61NEDDuSByLkGwJO69VQ>? M2LuS|I{PDR|OEC1
HEC155 NYL0d4lPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWWwTGh2UUN3ME2wMlY3KMLzIECuNFkh|ryP MViyN|Q1OzhyNR?=
MFE296 M37xbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV\lTlV{UUN3ME2wMlY3KMLzIECuNVkh|ryP MnH1NlM1PDN6MEW=
SPAC1S NGH5XHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnPTWM2OD1yLke3JOKyKDBwMEig{txO NIfmU3YzOzR2M{iwOS=>
RL952 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnubVZKSzVyPUCuPVMhyrFiMD6wNUDPxE1? M2rvd|I{PDR|OEC1
EN1 MkniS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2rzfmlEPTB;MT6wNkDDuSByLkK1JO69VQ>? NUS5Ro1ROjN2NEO4NFU>
SNGII MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTFwMkSgxtEhOC5{ODFOwG0> Mn\ZNlM1PDN6MEW=
ISHIKAWA NUPQc3lPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfmeGFzUUN3ME2xMlMxKMLzIECuNVEh|ryP NHzYNnozOzR2M{iwOS=>
HEC1A NFnRd|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFHBbHVKSzVyPUGuN|QhyrFiMD6zNEDPxE1? M1i4OlI{PDR|OEC1
KLE M{O4bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2\JdGlEPTB;MT6zO{DDuSByLkCyJO69VQ>? NH3ZZ2MzOzR2M{iwOS=>
SNGM NGKwSoRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XE[GlEPTB;MT60NkDDuSByLkGzJO69VQ>? M1vWbFI{PDR|OEC1
USPC2 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M37XSGlEPTB;MT62NkDDuSByLkCxJO69VQ>? NEf3ZZkzOzR2M{iwOS=>
EN NXrneodWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlnTTWM2OD1zLk[2JOKyKDBwMEGg{txO M2m4[FI{PDR|OEC1
MFE319 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXWwSpNIUUN3ME2xMlg4KMLzIECuOFUh|ryP NHXIU|YzOzR2M{iwOS=>
EFE184 NI\5[nJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{OzfmlEPTB;Mj6wOEDDuSByLkGzJO69VQ>? MWmyN|Q1OzhyNR?=
ECC1 NV[4WFZZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzIfYxTUUN3ME2yMlA4KMLzIECuNFEh|ryP NIfKVokzOzR2M{iwOS=>
HEC1B MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVTJR|UxRTJwNUegxtEhOC5{MzFOwG0> MWCyN|Q1OzhyNR?=
USPC1 NGX0[5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX:1fVNKUUN3ME2yMlYxKMLzIECuNVMh|ryP MUiyN|Q1OzhyNR?=
SPAC1L NHLOPWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTNwME[gxtEhOS5zNDFOwG0> MXyyN|Q1OzhyNR?=
HUVEC MXnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NU\KSFN3OC1{NTFOwG0> NV3UNGdxPzJiaB?= MYrEUXNQ MXfpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> Mo[4NlMzOjhyMUe=
HMVEC MojPR4VtdCCYaXHibYxqfHliQYPzZZk> MWSwMVI2KM7:TR?= MWG3NkBp NHHYZ2RFVVOR NU\MSFVtcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NF;YVmUzOzJ{OECxOy=>
MHCC-97H M37rUGNmdGxiVnnhZoltcXS7IFHzd4F6 M4PqdVAuOjVizszN M13OPVczKGh? NE[4WmRFVVOR NFm3[5RqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MlTBNlMzOjhyMUe=
SMMC7721 NVHmWmtNS2WubDDWbYFjcWyrdImgRZN{[Xl? NXrUNVZlOC1{NTFOwG0> MUK3NkBp MWjEUXNQ NGPMTnRqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? Moe5NlMzOjhyMUe=
Huh-7 NWjq[HY5SXCxcITvd4l{KEG|c3H5 M1jQdVAuOTJwNTFOwG0> MofHNlQhcA>? NUL1d|RKTE2VT9Mg NGHNUHd{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz MXKyNlI{ODR5OR?=
Sk-Hep1 MnLZRZBweHSxc3nzJGF{e2G7 Ml;aNE0yOi53IN88US=> NEfIepUzPCCq NXHrfGdTTE2VT9Mg Mlf4d4Vve2m2aYrld{BJS0NiY3XscJMhfG9iVGLBTWwuKGGwZDD0bYdifHW8dX3hZk1qdmS3Y3XkJIFxd3C2b4Ppd{BqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> MVeyNlI{ODR5OR?=
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PLC5 M1S5SGFxd3C2b4Ppd{BCe3OjeR?= MVGwMVEzNjVizszN NYfnWpdxOjRiaB?= M13kR2ROW00EoB?= M4fzTpNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NX\WT5BLOjJ{M{C0O|k>
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PLC5 NX7uc3k6SXCxcITvd4l{KEG|c3H5 NY\kOIQyOC1zNTFOwG0> NUHqT4F[OjRiaB?= NYryfGNOcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MnHwNlIyQDB|MEi=
Hep3B MmX2RZBweHSxc3nzJGF{e2G7 M1r4PVAuOTVizszN MX2yOEBp MnjnbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NWK1WlR7OjJzOECzNFg>
Sk-Hep1 MUjBdI9xfG:|aYOgRZN{[Xl? MUGwMVE2KM7:TR?= MU[yOEBp NV3Ob5RzcW6lcnXhd4V{KGGyb4D0c5Rq[yClZXzsJIRm[XSqIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= MlXNNlIyQDB|MEi=
Huh-7 NH7ve5pCeG:ydH;zbZMhSXO|YYm= Ml72NE0yPSEQvF2= MV6yOEBp NF\LR2hqdmO{ZXHz[ZMh[XCxcITveIlkKGOnbHyg[IVifGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MnrVNlIyQDB|MEi=
PLC5 MUDGeY5kfGmxbjDBd5NigQ>? NFLXUIwxNTFyIN88US=> NUnDTYlFOjRiaB?= MmLvZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v MojPNlIyQDB|MEi=
Hep3B NFj2SolHfW6ldHnvckBCe3OjeR?= NFS3cWcxNTFyIN88US=> MV2yOEBp MUHjZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> M3\5cFIzOThyM{C4
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Huh-7 NXXBZmxJTnWwY4Tpc44hSXO|YYm= NFHhPGsxNTFyIN88US=> MkTONlQhcA>? MlLSZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v Ml;uNlIyQDB|MEi=
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RT112 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGLlcmg2KGR? MnnUTWM2OD1zNTDuUS=> MnrHNlEyOTl4NkG=
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97-7 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nsU|Uh\A>? NX7HU|BxUUN3ME2xNFAxKG6P MoC2NlEyOTl4NkG=
RT112 Mly0SpVv[3Srb36gRZN{[Xl? NULyXVFCPTByIH7N MlLqNlQhcA>? NHqySnpqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= Mn\iNlEyOTl4NkG=
RT4 NHO5V5hHfW6ldHnvckBCe3OjeR?= MkDyOVAxKG6P MYeyOEBp Mk\6bY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| M2qzeFIyOTF7Nk[x
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 J807C NV36U|VvS2WubDDWbYFjcWyrdImgRZN{[Xl? NHzxT4oxNTRyMDDuUS=> MoryOFghcA>? M1;vPIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MX2xOVU6QDhzNB?=
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K650E MWLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NIHVd3MxNTRyMDDuUS=> MnXlOFghcA>? MWrpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NX3iOIxHOTV3OUi4NVQ>
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8226 MoPyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnXMO|IhcA>? NIjPXphKSzVyPjCyOVAxKG6P NEHJV4IyPTV7OEixOC=>
U266 MlHxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nZOlczKGh? M3KxOGlEPTB-IEK1NFAhdk1? MXOxOVU6QDhzNB?=

... Click to View More Cell Line Experimental Data

In vivo試験 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]
臨床試験 Dovitinib has entered in a phase II clinical trial for the treatment of adenoid cystic carcinoma.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [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.

細胞アッセイ: [1]

細胞株 B9 cells, MM cell lines
濃度 100 nM
反応時間 48-96 hours
実験の流れ 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.

動物実験: [1]

動物モデル 8-week-old female BNX mice bearing KMS11 cells
製剤 5 mM citrate buffer
投薬量 10, 30, or 60 mg/kg
投与方法 Gavage

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Dovitinib (TKI-258, CHIR-258) SDF
分子量 392.43
化学式

C21H21FN6O

CAS No. 405169-16-6
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 30 mg/mL (76.44 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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.
化学名 1-amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one

文献中の引用 (7)

技術サポート&よくある質問(FAQ)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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