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。

価格 在庫  
USD 214 あり
USD 240 あり
USD 340 あり
USD 592 あり

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

高品質保証

カスタマーフィードバック(7)

MSDS

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 M3PRVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVHXfHA5UUN3ME2wMlQ1QSEQvF2= NF;JcVIzPTJyMkC3Ny=>
SupB15-R NYXHU2d5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPNT3FQUUN3ME2wMlU2QCEQvF2= M2LJSlI2OjB{MEez
BaF3-pSRα MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFXOeFRKSzVyPUCuOlY5KM7:TR?= MmjnNlUzODJyN{O=
BaF3-p210Bcr-Abl NF\3NXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnHOTWM2OD1yLk[5NkDPxE1? Ml;wNlUzODJyN{O=
BaF3-p210Bcr-Abl-T315I MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4rWN2lEPTB;Mj62NlYh|ryP NHO2eHYzPTJyMkC3Ny=>
CCRF-CEM MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LSb2lEPTB;MD6zPVgh|ryP Mo\BNlUzODJyN{K=
CEM/C2 NGDC[|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\MTWM2OD1zLkGyOUDPxE1? MlfONlUzODJyN{K=
Nalm-6 MorQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV7JR|UxRTBwM{iyJO69VQ>? MkfRNlUzODJyN{K=
SEM-K2 NIjhZ|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV7JR|UxRTBwMEKyJO69VQ>? NUnWXlA5OjV{MEKwO|I>
HB-1119 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTBwMEK4JO69VQ>? M4rtTlI2OjB{MEey
RS4:11 NInUd5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{LsRmlEPTB;Mj64NUDPxE1? M4D2NFI2OjB{MEey
Nalm-6 NIXReYRCeG:ydH;zbZMhSXO|YYm= NHLMZ3kzKM7:TR?= NWXIOnQzOjRxNEigbC=> M4nBcolv\HWlZYOgZZBweHSxc3nzJJJme3WudHnu[{BqdiCjYn;1eEA4OiVib3[gZ4VtdCCmZXH0bEBi\nSncjCyOEBpKHS{ZXH0cYVvfCCjbnSgPFEmKGGodHXyJFQ5KGh? M17vdVI2OjB{MEey
SEM-K2 MWTBdI9xfG:|aYOgRZN{[Xl? MVywMlEwOSEQvF2= MlPlNlQhcA>? Mm\lbY5lfWOnczDlZZJtgSCjcH;weI9{cXNib3[gV2VONUt{IHPlcIx{KGG2IECuNUDPxE1iYX\0[ZIhOjRiaB?= MlHKNlUzODJyN{K=
HCT-116 NUGxfmlXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknITWM2OD1|LkC1NE42QCEQvF2= M{TPSlI1PDl3N{Ww
HT-29 MnTpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFPRUYxKSzVyPUWuNlEvQTNizszN NHzwc4QzPDR7NUe1NC=>
SW-480 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13VO2lEPTB;ND6zN|AvPDdizszN MkPxNlQ1QTV5NUC=
CaCO2 M3\GXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTNwMkOwMlY1KM7:TR?= MmXPNlQ1QTV5NUC=
LS174T MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEXoSHZKSzVyPUSuN|MxNjR5IN88US=> MkjRNlQ1QTV5NUC=
HEC-1A NXq3fmUyTnWwY4Tpc44hSXO|YYm= M3zkTlAvODVxMD6xM|AvPSEQvF2= M4rzclczKGh? NV\RflRG[2G3c3XzJIEh\GWlcnXhd4UhcW5iU2TBWFMtKEWUSzygZY5lKEGNVDDwbI9{eGixconsZZRqd25? M2DTeVI1PDl3N{Ww
AN3CA M{joVmZ2dmO2aX;uJGF{e2G7 MUmwMlA2NzBwMT:wMlUh|ryP NX7nTI5XPzJiaB?= M1zrTINifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v M376WFI1PDl3N{Ww
MFE-296  MlHJSpVv[3Srb36gRZN{[Xl? Mn3CNE4xPS9yLkGvNE42KM7:TR?= MXu3NkBp NFrJdW1k[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? MWeyOFQ6PTd3MB?=
UMC3 NUfkRm4yS2WubDDWbYFjcWyrdImgRZN{[Xl? MkDRNU0yOCEQvF2= NH7kWJk4OiCq NVLMUGc{cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MkKwNlQ{OjV2NkG=
5637 NEmycIZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MXWxMVExKM7:TR?= M3vNeVczKGh? MYfpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NHiwZY0zPDN{NUS2NS=>
HU456 NGLjN5FE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NWPNV2lXOS1zMDFOwG0> NIPSOpQ4OiCq MVXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NUC0VJdlOjR|MkW0OlE>
MGHU4 M3HxXmNmdGxiVnnhZoltcXS7IFHzd4F6 M{jST|EuOTBizszN NYHmNJFKPzJiaB?= MlnCbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MUiyOFMzPTR4MR?=
HT1376 NF32R4VE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M3jNeFEuOTBizszN NEH6OGY4OiCq MkP2bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M1rsZ|I1OzJ3NE[x
RT112 MXfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M{nSXFEuOTBizszN NGC5XHQ4OiCq MVjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NIHCSVEzPDN{NUS2NS=>
T24 M2noPGNmdGxiVnnhZoltcXS7IFHzd4F6 NGrtO5EyNTFyIN88US=> NI\keWw4OiCq NU\qfFk1cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MkS1NlQ{OjV2NkG=
BFTC905 Ml\5R4VtdCCYaXHibYxqfHliQYPzZZk> NXjLeIVVOS1zMDFOwG0> MV:3NkBp MmHYbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MomwNlQ{OjV2NkG=
TCC-SUP MoTwR4VtdCCYaXHibYxqfHliQYPzZZk> MUSxMVExKM7:TR?= M{fBXlczKGh? MV\pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> Mnz6NlQ{OjV2NkG=
RT4 MYHD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MkPINU0yOCEQvF2= NXzNT3N2PzJiaB?= NHvtRmFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NGP3cFczPDN{NUS2NS=>
HONE1 M3TGOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWLWfm5uOC5zLUGwJO69VQ>? MYK0POKhcA>? NXf1NYNIcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz M4THd|I1OjN6MEm0
HNE1 NV7EcmpST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUmwMlEuOTBizszN MmToOFjDqGh? MVLpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= MW[yOFI{QDB7NB?=
CNE2  MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYGwMlEuOTBizszN NHfjU4o1QMLiaB?= NVf5[4J2cW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NYPGOFUzOjR{M{iwPVQ>
C666-1 NFq5PWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnLbG0xNjFvMUCg{txO M3WyclQ5yqCq MWfpcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= NYjSeos4OjR{M{iwPVQ>
HeLa NGrCfppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3foOFAvOS1zMDFOwG0> MWOyOEBp MXjpcoR2[2W|IFeyM20h[XK{ZYP0JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy M3i0S|I1OjN6MEm0
Hep3B M1[2PGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;tXFAvOS1zMDFOwG0> M1fLdFI1KGh? NH\VR2tqdmS3Y3XzJGczyqCjcoLld5TDqA>? MnzCNlQzOzhyOUS=
HepG2 MkD6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2TIS|Q5KGh? MmXDTWM2OD1{LkeyO{DDuSByLkSyPUDPxE1? M4XvW|I{PTR4NUmx
Hep3B M1jaeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\lVFQ5KGh? MkLiTWM2OD12LkKyN{DDuSByLkizPUDPxE1? MmnGNlM2PDZ3OUG=
PLC/PRF5 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorpOFghcA>? M2ftZWlEPTB;MU[uNVIxKMLzIESuNFAyKM7:TR?= NGfsPIQzOzV2NkW5NS=>
Huh7 NWn2cWNoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmPNOFghcA>? NUDlc3FpUUN3ME2xOU4xODdiwsGgO{4{OzRizszN MkL3NlM2PDZ3OUG=
HepG2 MnjmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoDGO|IhcA>? MmrkTWM2OD1zLkKwNEDDuSByLkKyOkDPxE1? NUPxcHdUOjN3NE[1PVE>
Hep3B M2DyO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\zeW5rPzJiaB?= NWrJXG5xUUN3ME2wMlg6OiEEsTCwMlA1PCEQvF2= M4LHOlI{PTR4NUmx
PLC/PRF5 NUf6dmJ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIPLRmI4OiCq M{HqUWlEPTB;Mz6xNVAhyrFiMD6zN|ch|ryP MWWyN|U1PjV7MR?=
Huh7 MlXES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUO3NkBp NIryZlJKSzVyPUOuPVgxKMLzIECuPFA{KM7:TR?= MXiyN|U1PjV7MR?=
MFE280 Mo[3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEnNWWJKSzVyPUCuOFIhyrFiMD6wOkDPxE1? NWH3NIFzOjN2NEO4NFU>
AN3CA M1LJU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTBwNUCgxtEhOC5zMDFOwG0> M4rCOlI{PDR|OEC1
HEC155 M3fWVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYq4OGp5UUN3ME2wMlY3KMLzIECuNFkh|ryP MlPXNlM1PDN6MEW=
MFE296 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVrxWIlRUUN3ME2wMlY3KMLzIECuNVkh|ryP MnfBNlM1PDN6MEW=
SPAC1S Moi2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYPJR|UxRTBwN{egxtEhOC5yODFOwG0> MnvSNlM1PDN6MEW=
RL952 NWTnZmcyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYHJR|UxRTBwOUOgxtEhOC5yMTFOwG0> M13nfFI{PDR|OEC1
EN1 M3[yZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFy5T3FKSzVyPUGuNFIhyrFiMD6yOUDPxE1? MlvFNlM1PDN6MEW=
SNGII NYTPN2xjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWLJR|UxRTFwMkSgxtEhOC5{ODFOwG0> M163dlI{PDR|OEC1
ISHIKAWA Mn3FS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYHJR|UxRTFwM{CgxtEhOC5zMTFOwG0> NWXvenR1OjN2NEO4NFU>
HEC1A M{HSbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3v4NGlEPTB;MT6zOEDDuSByLkOwJO69VQ>? MYOyN|Q1OzhyNR?=
KLE Mn7tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HRdmlEPTB;MT6zO{DDuSByLkCyJO69VQ>? Mn25NlM1PDN6MEW=
SNGM MnHuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2TyU2lEPTB;MT60NkDDuSByLkGzJO69VQ>? NHHodmwzOzR2M{iwOS=>
USPC2 MoPvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVfQU4dpUUN3ME2xMlYzKMLzIECuNFEh|ryP MoixNlM1PDN6MEW=
EN MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{\D[mlEPTB;MT62OkDDuSByLkCxJO69VQ>? MWiyN|Q1OzhyNR?=
MFE319 M{jnW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTFwOEegxtEhOC52NTFOwG0> Ml\ZNlM1PDN6MEW=
EFE184 MnGzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWex[25uUUN3ME2yMlA1KMLzIECuNVMh|ryP MUSyN|Q1OzhyNR?=
ECC1 NGHobJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm[4TWM2OD1{LkC3JOKyKDBwMEGg{txO MnTCNlM1PDN6MEW=
HEC1B MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTJwNUegxtEhOC5{MzFOwG0> M{XneFI{PDR|OEC1
USPC1 M3Xy[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWTJR|UxRTJwNkCgxtEhOC5zMzFOwG0> MkXkNlM1PDN6MEW=
SPAC1L MofGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlTGTWM2OD1|LkC2JOKyKDFwMUSg{txO NV3me5RkOjN2NEO4NFU>
HUVEC MonOR4VtdCCYaXHibYxqfHliQYPzZZk> NWjDWXd7OC1{NTFOwG0> NYTUeW9YPzJiaB?= NYjwXoZTTE2VTx?= NWL0cYJEcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? M4LVN|I{OjJ6MEG3
HMVEC MYXD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NVrzO44{OC1{NTFOwG0> NX7JfZU1PzJiaB?= MYDEUXNQ NHjjWFhqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MXmyN|IzQDBzNx?=
MHCC-97H NEiyRWZE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MoXqNE0zPSEQvF2= MknpO|IhcA>? MkS2SG1UVw>? MnjGbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> NV\Ub3lTOjN{MkiwNVc>
SMMC7721 M2q2dGNmdGxiVnnhZoltcXS7IFHzd4F6 NX;4d|RQOC1{NTFOwG0> MYC3NkBp MVrEUXNQ M{jtWYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz MYiyN|IzQDBzNx?=
Huh-7 NFmyPWdCeG:ydH;zbZMhSXO|YYm= M2XDclAuOTJwNTFOwG0> NIj3TVYzPCCq NHXnNJhFVVORwrC= M{DuepNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> MnfqNlIzOzB2N{m=
Sk-Hep1 M2naemFxd3C2b4Ppd{BCe3OjeR?= NUjMUI8xOC1zMj61JO69VQ>? NVezVHp{OjRiaB?= NUT6TZF3TE2VT9Mg MXXz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NIC1e4szOjJ|MES3PS=>
Hep3B NHnzdZpCeG:ydH;zbZMhSXO|YYm= NH\ubHcxNTF{LkWg{txO NYHhbYM{OjRiaB?= M1ix[WROW00EoB?= MVzz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy M3i1TFIzOjNyNEe5
PLC5 MW\BdI9xfG:|aYOgRZN{[Xl? MnK1NE0yOi53IN88US=> Ml\1NlQhcA>? MVLEUXNQyqB? NYHne3Zpe2Wwc3n0bZpmeyCKQ1OgZ4VtdHNidH:gWHJCUUxvIHHu[EB1cWejdIX6eY1i[i2rbnT1Z4VlKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? NVvQNI0zOjJ{M{C0O|k>
PLC5 MlziR4VtdCCYaXHibYxqfHliQYPzZZk> MXewMVE2KM7:TR?= NUDSOG1UPzJiaB?= M{LEVpJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MmnFNlIyQDB|MEi=
Hep3B NF7aPHlE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVPBSnpQOC1zNTFOwG0> M1ziWFczKGh? M4TGcZJm\HWlZYOgZ4VtdCC4aXHibYxqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XMEoB?= MonpNlIyQDB|MEi=
Sk-Hep1 MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MkHUNE0yPSEQvF2= M3HRRVczKGh? NIq2XmVz\WS3Y3XzJINmdGxidnnhZoltcXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{wrC= M4fncFIzOThyM{C4
Huh-7 MkS3R4VtdCCYaXHibYxqfHliQYPzZZk> M1z0OlAuOTVizszN NWfEU2k4PzJiaB?= Mkn0doVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M3m2O|IzOThyM{C4
PLC5 NUDDfnI{SXCxcITvd4l{KEG|c3H5 MmHsNE0yPSEQvF2= MnK4NlQhcA>? M{S2dYlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M2\sO|IzOThyM{C4
Hep3B MmDGRZBweHSxc3nzJGF{e2G7 Ml;vNE0yPSEQvF2= NWTpTHBPOjRiaB?= M4O5cIlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi M4DJU|IzOThyM{C4
Sk-Hep1 MXXBdI9xfG:|aYOgRZN{[Xl? MUWwMVE2KM7:TR?= Mmj0NlQhcA>? MX;pcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? NFrTR2szOjF6MEOwPC=>
Huh-7 M1XNVGFxd3C2b4Ppd{BCe3OjeR?= MmDnNE0yPSEQvF2= NGX5SJozPCCq MV7pcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? NXfDbFNrOjJzOECzNFg>
PLC5 NF\scYJHfW6ldHnvckBCe3OjeR?= MW[wMVExKM7:TR?= Mnz3NlQhcA>? MU\jZZV{\XNiZH;z[U1l\XCnbnTlcpQhTE6DIH\yZYdu\W62YYTpc44> M4S0V|IzOThyM{C4
Hep3B MWHGeY5kfGmxbjDBd5NigQ>? M2PROlAuOTBizszN MVmyOEBp NEiwNFBk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? M4Xyc|IzOThyM{C4
Sk-Hep1 NETJ[mlHfW6ldHnvckBCe3OjeR?= MXWwMVExKM7:TR?= NGW5PGgzPCCq MmjuZ4F2e2W|IHTvd4Uu\GWyZX7k[Y51KESQQTDmdoFodWWwdHH0bY9v NWLkcIpOOjJzOECzNFg>
Huh-7 NImzRnlHfW6ldHnvckBCe3OjeR?= NWjmeIhIOC1zMDFOwG0> NFvM[lQzPCCq NE\DRXdk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NY\CTWFzOjJzOECzNFg>
SW780 MkK3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHvFdWQ2KGR? M4G5O2lEPTB;NUCgcm0> MYSyNVEyQTZ4MR?=
RT112 NEXmTmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1j4S|Uh\A>? MnnRTWM2OD1zNTDuUS=> NEnRN2UzOTFzOU[2NS=>
RT4 MlnNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnT3OUBl M3uxZ2lEPTB;NTDuUS=> M1zIc|IyOTF7Nk[x
JMSU1 Mnr6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfqfnc2KGR? M4rudGlEPTB;NUCgcm0> M{Dab|IyOTF7Nk[x
J82 NHrmflRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojPOUBl NXPMbHM5UUN3ME2xOFAxKG6P NGXjWnkzOTFzOU[2NS=>
97-7 NIPROppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoD0OUBl M{LCW2lEPTB;MUCwNEBvVQ>? MmTQNlEyOTl4NkG=
RT112 MVfGeY5kfGmxbjDBd5NigQ>? MX:1NFAhdk1? MlvDNlQhcA>? MlrMbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| NH3WUVAzOTFzOU[2NS=>
RT4 M4LsdmZ2dmO2aX;uJGF{e2G7 NWLsdFBsPTByIH7N NWLqXlZKOjRiaB?= M4P3WIlv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MkfLNlEyOTl4NkG=
MGH-U3 NEC1c3VHfW6ldHnvckBCe3OjeR?= NV3ZNmNOPTByIH7N NGDMd3MzPCCq NE\kOVhqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= NFfHfZozOTFzOU[2NS=>
SW780 Mmf6SpVv[3Srb36gRZN{[Xl? M2jBOFUxOCCwTR?= NGqwZlAzPCCq NF7S[mFqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MXWyNVEyQTZ4MR?=
97-7 MnLqSpVv[3Srb36gRZN{[Xl? NGewbok2ODBibl2= NFi3[WYzPCCq MojUbY5kemWjc3XzJJRp\SCycn;wc5J1cW:wIH;mJINmdGy|IHnuJGcyyqCjY3PvcZBidmmnZDDifUBiKGSnY4LlZZNmKGmwIGOgZY5lKEd{L12gdIhie2W| M2rSN|IyOTF7Nk[x
 J807C MX7D[YxtKF[rYXLpcIl1gSCDc4PhfS=> M4jDPFAuPDByIH7N MXO0PEBp MkjlbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MV[xOVU6QDhzNB?=
Y373C MUDD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M1;ofFAuPDByIH7N M{\EPFQ5KGh? MWXpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MYexOVU6QDhzNB?=
K650E NXvoUoJNS2WubDDWbYFjcWyrdImgRZN{[Xl? MWGwMVQxOCCwTR?= MmLhOFghcA>? NF;tflVqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MUSxOVU6QDhzNB?=
G384D NH;JWndE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MVGwMVQxOCCwTR?= MXi0PEBp Mlf6bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MVyxOVU6QDhzNB?=
F384L MnjiR4VtdCCYaXHibYxqfHliQYPzZZk> NY\mO2lVOC12MECgcm0> NIHuZW01QCCq NWPFOWd{cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? MmCwNVU2QTh6MUS=
KMS11 M1HtSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonMO|IhcA>? NIKzUZdKSzVyPUmwJI5O M4HTeFE2PTl6OEG0
KMS18 NGfDd5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDv[3lxPzJiaB?= M13pUWlEPTB;NUWwJI5O M1vUc|E2PTl6OEG0
OPM2 NFPtSWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MorRO|IhcA>? M3vK[WlEPTB;OUCgcm0> M1nvSFE2PTl6OEG0
H929 NXnI[5JrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2DVbFczKGh? MXjJR|UxRiB{NUCwJI5O NWDPWVNqOTV3OUi4NVQ>
8226 NWrBclE6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Moj2O|IhcA>? MoLrTWM2OD5iMkWwNEBvVQ>? M4DCUFE2PTl6OEG0
U266 NXnFN4NFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGjKdYc4OiCq NXLPOYhJUUN3ME6gNlUxOCCwTR?= M2fhbVE2PTl6OEG0

... 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)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related FLT3 阻害剤

  • Dovitinib (TKI258) Lactate

    Dovitinib (TKI258) Lactateは一種の「 Dovitinib」の乳酸塩で、一種の多ターゲットRTK阻害剤で、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) Lactate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。

  • AMG 925

    AMG 925は一種の有効で、経口生物利用可能な二重FLT3/CDK4阻害剤で、IC50値が1 nM と3 nMです。

  • PX-478 2HCl

    PX-478 2HClは一種の経口活性をしている、選択性的なHIF-1α阻害剤です。臨床1期。

  • Defactinib (VS-6063, PF-04554878)

    Defactinib (VS-6063, PF-04554878)は一種の選択性的で、経口有効なFAK阻害剤です。臨床2期。

  • Quizartinib (AC220)

    Quizartinib (AC220)は一種の第二代FLT3阻害剤で、MV4-11と RS411細胞にFlt3(ITD/WT)に作用する時のIC50値が1.1 nM/4.2 nMです。Quizartinib (AC220)は、Flt3に作用する選択性はKIT、PDGFRA、PDGFRB、RETとCSF-1Rに作用する選択性より10倍が高くなります。臨床3期。

    Features:The most potent cellular FLT3-ITD inhibitor.

  • ENMD-2076

    ENMD-2076はオーロラ AとVEGFR(Flt3)を選択性的に作用して、IC50値が14 nMと1.86 nMにそれぞれ分かれますが、オーロラ Aに作用する選択性はオーロラBに作用する選択性より25倍が高くなって、VEGFR2/KDR、VEGFR3、FGFR1とFGFR2とPDGFRαに作用する効果が少し弱くなります。臨床2期。

    Features:Multi-target, anti-proliferative, pro-apoptotic activity, anti-angiogenic.

  • KW-2449

    KW-2449は一種の多ターゲット阻害剤です。KW-2449はFlt3に作用する効果が一番強くて、IC50値が6.6 nMになりますが、FGFR1、Bcr-Abl とオーロラ Aに適度に作用して、PDGFRβ、IGF-1RとEGFRを抑制する効果がありません。臨床1期。

    Features:Investigated as a FLT3 inhibitor in clinical trials, with others in early development.

  • Tandutinib (MLN518)

    Tandutinib (MLN518)は一種の有効なFLT3拮抗剤で、IC50値が0.22 μMです。Tandutinib (MLN518)は同時にPDGFRとc-Kitを抑制して、FLT3に作用する効果はCSF-1Rに作用する効果より15倍-20倍が高くなって、FGFR、EGFRとKDRに作用する効果より100倍以上が高くなります。臨床2期。

  • Dovitinib (TKI-258) Dilactic Acid

    Dovitinib Dilactic acid (TKI258 Dilactic acid)は一種の「 Dovitinib」のDilactic acidで、一種の多ターゲットRTK阻害剤で、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 Dilactic acid (TKI258 Dilactic acid)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。

最近チェックしたアイテム

Tags: Dovitinib (TKI-258, CHIR-258)を買う | Dovitinib (TKI-258, CHIR-258)供給者 | Dovitinib (TKI-258, CHIR-258)を購入する | Dovitinib (TKI-258, CHIR-258)費用 | Dovitinib (TKI-258, CHIR-258)生産者 | オーダーDovitinib (TKI-258, CHIR-258) | Dovitinib (TKI-258, CHIR-258)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ