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
電話番号: + 81 3-5632-9610mail@cosmobio.co.jp

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 MmLoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGHZOndKSzVyPUCuOFQ6KM7:TR?= M1fSUVI2OjB{MEez
SupB15-R M1S3Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWjJR|UxRTBwNUW4JO69VQ>? M2CxS|I2OjB{MEez
BaF3-pSRα NInifGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3KTHJKSzVyPUCuOlY5KM7:TR?= NY\UOWZWOjV{MEKwO|M>
BaF3-p210Bcr-Abl Mlq5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVPJR|UxRTBwNkmyJO69VQ>? M4nkWVI2OjB{MEez
BaF3-p210Bcr-Abl-T315I NXu2SZdYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHVTW5KSzVyPUKuOlI3KM7:TR?= M3rye|I2OjB{MEez
CCRF-CEM NVXVeHI5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVXJR|UxRTBwM{m4JO69VQ>? NYmxT4JFOjV{MEKwO|I>
CEM/C2 MljPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3[yNWlEPTB;MT6xNlUh|ryP MnPXNlUzODJyN{K=
Nalm-6 Mn6xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfETWM2OD1yLkO4NkDPxE1? M4\3bVI2OjB{MEey
SEM-K2 MnT5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2XCVmlEPTB;MD6wNlIh|ryP M4nTXVI2OjB{MEey
HB-1119 M3LJW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3PVeWlEPTB;MD6wNlgh|ryP NXHoWXkzOjV{MEKwO|I>
RS4:11 NUXLVopGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{W5NWlEPTB;Mj64NUDPxE1? Mlr3NlUzODJyN{K=
Nalm-6 M4jGO2Fxd3C2b4Ppd{BCe3OjeR?= M13INlIh|ryP NInPWI0zPC92ODDo MXrpcoR2[2W|IHHwc5B1d3OrczDy[ZN2dHSrbnegbY4h[WKxdYSgO|ImKG:oIHPlcIwh\GWjdHigZYZ1\XJiMkSgbEB1emWjdH3lcpQh[W6mIEixKUBi\nSncjC0PEBp MmnGNlUzODJyN{K=
SEM-K2 M1PCVWFxd3C2b4Ppd{BCe3OjeR?= MmnpNE4yNzFizszN M2DxW|I1KGh? NH:xTW5qdmS3Y3XzJIViemy7IHHwc5B1d3OrczDv[kBUTU1vS{KgZ4VtdHNiYYSgNE4yKM7:TTDh[pRmeiB{NDDo NFPiSnEzPTJyMkC3Ni=>
HCT-116 M3\j[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvCPJJFUUN3ME2zMlA2OC53ODFOwG0> NFv5bnQzPDR7NUe1NC=>
HT-29 M1H1N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWLJR|UxRTVwMkGuPVMh|ryP M4fUU|I1PDl3N{Ww
SW-480 NXTVOWlpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVHqdZhoUUN3ME20MlM{OC52NzFOwG0> MkPzNlQ1QTV5NUC=
CaCO2 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NILGcZNKSzVyPUOuNlMxNjZ2IN88US=> NHPHcHYzPDR7NUe1NC=>
LS174T NWi5WZYzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGC4NnBKSzVyPUSuN|MxNjR5IN88US=> M3HSO|I1PDl3N{Ww
HEC-1A NWfydIM{TnWwY4Tpc44hSXO|YYm= MWOwMlA2NzBwMT:wMlUh|ryP Ml3NO|IhcA>? M2e0OINifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v MYmyOFQ6PTd3MB?=
AN3CA M1fibWZ2dmO2aX;uJGF{e2G7 MkLXNE4xPS9yLkGvNE42KM7:TR?= M{DPblczKGh? NH;zcmNk[XW|ZYOgZUBl\WO{ZXHz[UBqdiCVVFHUN{whTVKNLDDhcoQhSUuWIIDoc5NxcG:{eXzheIlwdg>? MWGyOFQ6PTd3MB?=
MFE-296  Mn7ZSpVv[3Srb36gRZN{[Xl? NWPrXVFXOC5yNT:wMlEwOC53IN88US=> MVO3NkBp M{\QV4NifXOnczDhJIRm[3KnYYPlJIlvKFOWQWSzMEBGWktuIHHu[EBCU1RicHjvd5Bpd3K7bHH0bY9v M{TQSFI1PDl3N{Ww
UMC3 Mkm5R4VtdCCYaXHibYxqfHliQYPzZZk> MWqxMVExKM7:TR?= NGH2Opk4OiCq M331XYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz Mmm1NlQ{OjV2NkG=
5637 NH2yR29E\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1H3c|EuOTBizszN MWm3NkBp MXHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NFz6T48zPDN{NUS2NS=>
HU456 Mn3CR4VtdCCYaXHibYxqfHliQYPzZZk> M3Hyb|EuOTBizszN MUe3NkBp NWTtV2JvcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? Mn7zNlQ{OjV2NkG=
MGHU4 M1zhOmNmdGxiVnnhZoltcXS7IFHzd4F6 MlO3NU0yOCEQvF2= M{LrTlczKGh? MlqxbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MojvNlQ{OjV2NkG=
HT1376 Mo\nR4VtdCCYaXHibYxqfHliQYPzZZk> M2Px[|EuOTBizszN M3XmT|czKGh? NHLKOVNqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? MUWyOFMzPTR4MR?=
RT112 MV\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> Mn7JNU0yOCEQvF2= M1zITVczKGh? M4PDTolvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NXPReYEzOjR|MkW0OlE>
T24 MW\D[YxtKF[rYXLpcIl1gSCDc4PhfS=> NYL3WJZROS1zMDFOwG0> NWr1N5NmPzJiaB?= MXLpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NUL3S3ozOjR|MkW0OlE>
BFTC905 MUjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M{fx[FEuOTBizszN MmLnO|IhcA>? NVvvTGtScW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NYKx[4E1OjR|MkW0OlE>
TCC-SUP NHyzTpFE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NXHqXWNyOS1zMDFOwG0> MWC3NkBp MoHobY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> M2m4TFI1OzJ3NE[x
RT4 Ml7XR4VtdCCYaXHibYxqfHliQYPzZZk> MorENU0yOCEQvF2= NEPYWJc4OiCq NYTsT3l2cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUBld3OnIHTldIVv\GWwdDDtZY5v\XJ? NWe1b2NtOjR|MkW0OlE>
HONE1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1mzUVAvOS1zMDFOwG0> MVe0POKhcA>? MoC5bY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy M1rHOFI1OjN6MEm0
HNE1 M4LDOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHrUOG0xNjFvMUCg{txO MWK0POKhcA>? MknsbY5lfWOnczDHNk9OKGSnbHH5JIlvKGFiY3;uZ4VvfHKjdHnvck1l\XCnbnTlcpQhdWGwbnXy NIS4[VEzPDJ|OEC5OC=>
CNE2  M{XS[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmHINE4yNTFyIN88US=> NFr3doY1QMLiaB?= MX;pcoR2[2W|IFeyM20h\GWuYYmgbY4h[SClb37j[Y51emG2aX;uMYRmeGWwZHXueEBu[W6wZYK= M3PXbFI1OjN6MEm0
C666-1 NETPUY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYewMlEuOTBizszN Mof4OFjDqGh? NULVUFhOcW6mdXPld{BIOi:PIHTlcIF6KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MXqyOFI{QDB7NB?=
HeLa MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX2wMlEuOTBizszN MUmyOEBp MkTibY5lfWOnczDHNk9OKGG{cnXzeEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MUCyOFI{QDB7NB?=
Hep3B NYrldWhRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1KzcVAvOS1zMDFOwG0> NYnUVnR7OjRiaB?= MlfKbY5lfWOnczDHNuKh[XK{ZYP0xsA> MUGyOFI{QDB7NB?=
HepG2 M1vMWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3vOd|Q5KGh? NGTFSpVKSzVyPUKuO|I4KMLzIECuOFI6KM7:TR?= MWmyN|U1PjV7MR?=
Hep3B MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\JOFghcA>? MUPJR|UxRTRwMkKzJOKyKDBwOEO5JO69VQ>? M1mwSFI{PTR4NUmx
PLC/PRF5 M2rtRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnj3OFghcA>? NUHlXWJKUUN3ME2xOk4yOjBiwsGgOE4xODFizszN NH\uTmQzOzV2NkW5NS=>
Huh7 NFHwXHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYW0PEBp NFnGN|VKSzVyPUG1MlAxPyEEsTC3MlM{PCEQvF2= MVuyN|U1PjV7MR?=
HepG2 NFvReFRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rLOFczKGh? NX\5UIxPUUN3ME2xMlIxOCEEsTCwMlIzPiEQvF2= M4Pvb|I{PTR4NUmx
Hep3B M2qwS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXfPT45WPzJiaB?= M4TLOmlEPTB;MD64PVIhyrFiMD6wOFQh|ryP Mn7uNlM2PDZ3OUG=
PLC/PRF5 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\YW4tQPzJiaB?= NYfEWnlZUUN3ME2zMlEyOCEEsTCwMlM{PyEQvF2= NUDZS4ZsOjN3NE[1PVE>
Huh7 M3n6emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVjSd4FMPzJiaB?= MmLJTWM2OD1|Lkm4NEDDuSByLkiwN{DPxE1? NVHBfnF[OjN3NE[1PVE>
MFE280 MnfuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGn2TnBKSzVyPUCuOFIhyrFiMD6wOkDPxE1? NVLqToVyOjN2NEO4NFU>
AN3CA NUjUcpB7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MofGTWM2OD1yLkWwJOKyKDBwMUCg{txO MWCyN|Q1OzhyNR?=
HEC155 NHvSXVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYKwWFBuUUN3ME2wMlY3KMLzIECuNFkh|ryP MlnmNlM1PDN6MEW=
MFE296 NXrEUFhDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYXofll6UUN3ME2wMlY3KMLzIECuNVkh|ryP NYKzW|hZOjN2NEO4NFU>
SPAC1S M1XIc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXHJR|UxRTBwN{egxtEhOC5yODFOwG0> MW[yN|Q1OzhyNR?=
RL952 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3ThOGlEPTB;MD65N{DDuSByLkCxJO69VQ>? NVPDRppsOjN2NEO4NFU>
EN1 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYrjTVBlUUN3ME2xMlAzKMLzIECuNlUh|ryP NEHvWpczOzR2M{iwOS=>
SNGII M2PMbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVzY[pU5UUN3ME2xMlI1KMLzIECuNlgh|ryP M2ft[FI{PDR|OEC1
ISHIKAWA M3zC[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4Hv[mlEPTB;MT6zNEDDuSByLkGxJO69VQ>? M3TVT|I{PDR|OEC1
HEC1A M3r0Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTFwM{SgxtEhOC5|MDFOwG0> Mon6NlM1PDN6MEW=
KLE NHS2flFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjpUoNKSzVyPUGuN|chyrFiMD6wNkDPxE1? MnTGNlM1PDN6MEW=
SNGM NUnIWWdQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWTJR|UxRTFwNEKgxtEhOC5zMzFOwG0> NVvCNZlJOjN2NEO4NFU>
USPC2 M2\sSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnfMTWM2OD1zLk[yJOKyKDBwMEGg{txO NXPyS3N[OjN2NEO4NFU>
EN M2m2S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1nH[mlEPTB;MT62OkDDuSByLkCxJO69VQ>? M4HVTlI{PDR|OEC1
MFE319 M2DJ[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4D6Z2lEPTB;MT64O{DDuSByLkS1JO69VQ>? NXvrRmlKOjN2NEO4NFU>
EFE184 NFSwVHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPDUpQ6UUN3ME2yMlA1KMLzIECuNVMh|ryP M3[2OVI{PDR|OEC1
ECC1 NIP2WoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MorlTWM2OD1{LkC3JOKyKDBwMEGg{txO NH7YVlgzOzR2M{iwOS=>
HEC1B NVLzSW45T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTmZZV3UUN3ME2yMlU4KMLzIECuNlMh|ryP M3naSFI{PDR|OEC1
USPC1 M{D5[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYjYUIt5UUN3ME2yMlYxKMLzIECuNVMh|ryP MXeyN|Q1OzhyNR?=
SPAC1L MlLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkiwTWM2OD1|LkC2JOKyKDFwMUSg{txO NF:3O|gzOzR2M{iwOS=>
HUVEC M364[GNmdGxiVnnhZoltcXS7IFHzd4F6 NXnGPG9yOC1{NTFOwG0> M{nvXlczKGh? NIDFbJdFVVOR M1i2V4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz NH3JUpczOzJ{OECxOy=>
HMVEC M1;KRmNmdGxiVnnhZoltcXS7IFHzd4F6 NFr2bHYxNTJ3IN88US=> M1nvO|czKGh? MVfEUXNQ NHGwRZFqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M2S0TlI{OjJ6MEG3
MHCC-97H NGnTV4RE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MVuwMVI2KM7:TR?= NIDtWWI4OiCq NUP5O2pETE2VTx?= MXjpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> MXiyN|IzQDBzNx?=
SMMC7721 MWPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NHHkZ5cxNTJ3IN88US=> MWS3NkBp NWDKdZc5TE2VTx?= MWfpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> M333PFI{OjJ6MEG3
Huh-7 M{P6[2Fxd3C2b4Ppd{BCe3OjeR?= NXi1eIhwOC1zMj61JO69VQ>? M1;UflI1KGh? MX7EUXNQyqB? NGjGSGd{\W6|aYTpfoV{KEiFQzDj[YxteyC2bzDUVmFKVC1iYX7kJJRq\2G2dYr1cYFjNWmwZIXj[YQh[XCxcITvd4l{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz MonnNlIzOzB2N{m=
Sk-Hep1 M1H2SGFxd3C2b4Ppd{BCe3OjeR?= NGjpdooxNTF{LkWg{txO M3;XUFI1KGh? MnTySG1UV8Li MWjz[Y5{cXSrenXzJGhESyClZXzsd{B1dyCWUlHJUE0h[W6mIITp[4F1fXq3bXHiMYlv\HWlZXSgZZBweHSxc3nzJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NVnsfVRSOjJ{M{C0O|k>
Hep3B Mli5RZBweHSxc3nzJGF{e2G7 M{TiPFAuOTJwNTFOwG0> NUSxO2tuOjRiaB?= M{LQfWROW00EoB?= M4[0fpNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NYTXVpo5OjJ{M{C0O|k>
PLC5 MUPBdI9xfG:|aYOgRZN{[Xl? MWewMVEzNjVizszN M13ObVI1KGh? Mo[3SG1UV8Li M1jJSZNmdnOrdHn6[ZMhUEOFIHPlcIx{KHSxIGTSRWlNNSCjbnSgeIlo[XS3eoXtZYIucW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI> NWS4UHdlOjJ{M{C0O|k>
PLC5 M1XzUWNmdGxiVnnhZoltcXS7IFHzd4F6 NWHySWZUOC1zNTFOwG0> NELreZk4OiCq Mmj5doVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi MXqyNlE5ODNyOB?=
Hep3B MmrpR4VtdCCYaXHibYxqfHliQYPzZZk> MoDDNE0yPSEQvF2= MUe3NkBp NX\Qb|NLemWmdXPld{Bk\WyuII\pZYJqdGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nctMg Ml6xNlIyQDB|MEi=
Sk-Hep1 M2\oTWNmdGxiVnnhZoltcXS7IFHzd4F6 NHS0[pExNTF3IN88US=> NUi1OGliPzJiaB?= MmHYdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NWXjTnVJOjJzOECzNFg>
Huh-7 NEHGdoJE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NH;j[JQxNTF3IN88US=> M2nPNFczKGh? MVzy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? M4fFNVIzOThyM{C4
PLC5 MYfBdI9xfG:|aYOgRZN{[Xl? M3nn[lAuOTVizszN M1\T[FI1KGh? M{nxNYlv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NFLOOXYzOjF6MEOwPC=>
Hep3B MkPVRZBweHSxc3nzJGF{e2G7 MoLKNE0yPSEQvF2= NE\TUHEzPCCq MmWxbY5kemWjc3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVzyqB? NHj5U4ozOjF6MEOwPC=>
Sk-Hep1 NWTDNW8zSXCxcITvd4l{KEG|c3H5 M{K2OVAuOTVizszN MlLMNlQhcA>? MXPpcoNz\WG|ZYOgZZBweHSxdHnjJINmdGxiZHXheIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZLDqA>? MWOyNlE5ODNyOB?=
Huh-7 NF\hPGxCeG:ydH;zbZMhSXO|YYm= MYWwMVE2KM7:TR?= MlzsNlQhcA>? M1npeolv[3KnYYPld{BieG:ydH;0bYMh[2WubDDk[YF1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5mesLi NXyx[lhHOjJzOECzNFg>
PLC5 NFXBOZRHfW6ldHnvckBCe3OjeR?= M17ncVAuOTBizszN NXy3eJJwOjRiaB?= NH\NfmJk[XW|ZYOg[I9{\S2mZYDlcoRmdnRiRF7BJIZz[WevZX70ZZRqd25? NVTtVY9sOjJzOECzNFg>
Hep3B NFWzT|ZHfW6ldHnvckBCe3OjeR?= NEixVZoxNTFyIN88US=> NI\sVpczPCCq NX71[VNJ[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NYjxUJZQOjJzOECzNFg>
Sk-Hep1 NXfqcVl6TnWwY4Tpc44hSXO|YYm= MWKwMVExKM7:TR?= M3n4Z|I1KGh? NVzXcYZo[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NHr0XlYzOjF6MEOwPC=>
Huh-7 NYTiZmdNTnWwY4Tpc44hSXO|YYm= NFrh[XcxNTFyIN88US=> MV6yOEBp NXjEVZZ2[2G3c3XzJIRwe2VvZHXw[Y5l\W62IFTORUBnemGpbXXueIF1cW:w NIjjZmIzOjF6MEOwPC=>
SW780 NFO3UYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnLOUBl MUPJR|UxRTVyIH7N NU\oeFF4OjFzMUm2OlE>
RT112 M2Kwdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;3c2o2KGR? NX3OdopOUUN3ME2xOUBvVQ>? M1rV[FIyOTF7Nk[x
RT4 NH[5V21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYO1JIQ> M2rV[2lEPTB;NTDuUS=> NXfqUVdxOjFzMUm2OlE>
JMSU1 MnrtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnz0OUBl MlrCTWM2OD13MDDuUS=> MXSyNVEyQTZ4MR?=
J82 M3X1U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHvOUBl MkDvTWM2OD1zNECwJI5O MX6yNVEyQTZ4MR?=
97-7 NFP0dXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV73T3VuPSCm MnTzTWM2OD1zMECwJI5O M1PJbVIyOTF7Nk[x
RT112 MmXDSpVv[3Srb36gRZN{[Xl? MnnoOVAxKG6P NW\0TZBCOjRiaB?= NH76OIxqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MXWyNVEyQTZ4MR?=
RT4 NI\mWZlHfW6ldHnvckBCe3OjeR?= NGrTWoE2ODBibl2= M4XBNlI1KGh? NGHqR|BqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MnfVNlEyOTl4NkG=
MGH-U3 MV;GeY5kfGmxbjDBd5NigQ>? MWq1NFAhdk1? NVO5WHc4OjRiaB?= M3nZdIlv[3KnYYPld{B1cGVicILvdI9zfGmxbjDv[kBk\WyuczDpckBIOcLiYXPjc41x[W6rZXSgZpkh[SCmZXPy[YF{\SCrbjDTJIFv\CCJMj;NJJBp[XOncx?= MVGyNVEyQTZ4MR?=
SW780 MU\GeY5kfGmxbjDBd5NigQ>? MoH4OVAxKG6P MUmyOEBp MYDpcoNz\WG|ZYOgeIhmKHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6gS|HDqGGlY3;tdIFvcWWmIHL5JIEh\GWlcnXhd4UhcW5iUzDhcoQhTzJxTTDwbIF{\XN? NHrweW4zOTFzOU[2NS=>
97-7 MofqSpVv[3Srb36gRZN{[Xl? MlvaOVAxKG6P NILLVXIzPCCq NHnZW5lqdmO{ZXHz[ZMhfGinIIDyc5BwenSrb36gc4Yh[2WubIOgbY4hTzIEoHHjZ49ueGGwaXXkJIJ6KGFiZHXjdoVie2ViaX6gV{BidmRiR{KvUUBxcGG|ZYO= MmH3NlEyOTl4NkG=
 J807C MoD6R4VtdCCYaXHibYxqfHliQYPzZZk> MoTzNE01ODBibl2= MnvSOFghcA>? M1ntZ4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\SCmZYDlcoRmdnRibXHucoVz M3H0NlE2PTl6OEG0
Y373C M2fCXWNmdGxiVnnhZoltcXS7IFHzd4F6 Mm[zNE01ODBibl2= M37CXlQ5KGh? NHrI[npqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? NFPDd2QyPTV7OEixOC=>
K650E MYPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NXPFTpJpOC12MECgcm0> MmDDOFghcA>? MUPpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=> NGj2bHgyPTV7OEixOC=>
G384D NUHHNHo2S2WubDDWbYFjcWyrdImgRZN{[Xl? NXq5WJVWOC12MECgcm0> MnnzOFghcA>? MmH4bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmKGSncHXu[IVvfCCvYX7u[ZI> MlTZNVU2QTh6MUS=
F384L M1PKN2NmdGxiVnnhZoltcXS7IFHzd4F6 M2LSb|AuPDByIH7N MkL1OFghcA>? NGe3OW1qdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2ViZHXw[Y5l\W62IH3hco5meg>? M4HZS|E2PTl6OEG0
KMS11 NIjuZXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzIO|IhcA>? M{GxeGlEPTB;OUCgcm0> NVTzU2p{OTV3OUi4NVQ>
KMS18 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkX6O|IhcA>? NGG1eY5KSzVyPUW1NEBvVQ>? MofENVU2QTh6MUS=
OPM2 MmDoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTyRZY4OiCq NX3LNWhXUUN3ME25NEBvVQ>? MkP6NVU2QTh6MUS=
H929 NUnle4d6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{S2VlczKGh? MX\JR|UxRiB{NUCwJI5O NFPWZZIyPTV7OEixOC=>
8226 MlW5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fjflczKGh? NYi0eI9{UUN3ME6gNlUxOCCwTR?= MoLPNVU2QTh6MUS=
U266 NHvxSHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3G1TlczKGh? M1jS[GlEPTB-IEK1NFAhdk1? M1rZVFE2PTl6OEG0

... 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