Bosutinib (SKI-606) 化学構造
分子量: 530.45

高品質保証

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Quality Control & MSDS

製品説明

  • Compare Src Inhibitors
    Src製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法
  • Bosutinib (SKI-606)のメカニズム

製品の説明

生物活性

製品説明 Bosutinib(SKI-606)はそれぞれ1.2nMと1nMのIC50値による新しい二重Sarcoma/アベルソン(Src/Abl)チロシン・キナーゼ阻害剤です。
ターゲット

Src

Abl

IC50

1.2 nM [1]

1 nM [2]

In vitro試験 Bosutinib is selective for Src over non-Src family kinases with an IC50 of 1.2 nM, and potently inhibits Src-dependent cell proliferation with an IC50 of 100 nM. [1] Bosutinib significantly inhibits the proliferation of Bcr-Abl-positive leukemia cell lines KU812, K562, and MEG-01 but not Molt-4, HL-60, Ramos, and other leukemia cell lines, with IC50 of 5 nM, 20 nM and 20 nM, respectively, more potently than that of STI-571. Similar to STI-571, Bosutinib displays antiproliferative activity against the Abl-MLV-transformed fibroblasts with IC50 of 90 nM. Bosutinib ablates tyrosine phosphorylation of Bcr-Abl and STAT5 in CML cells and of v-Abl expressed in fibroblasts at the concentration of ~50 nM, 10-25 nM and 200 nM, respectively, leading to the Bcr-Abl downstream signaling inhibition of Lyn/Hck phosphorylation. [2] Although unable to inhibit the proliferation and survival of breast cancer cells, Bosutinib significantly decreases the motility and invasion of breast cancer cells with IC50 of ~250 nM, involved with an increase in cell-to-cell adhesion and membrane localization of β-catenin. [3]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
NB7 NVjWNnFPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjTfVFKSzVyPUCuNFgzOzFiIN88US=> M3v2VXNCVkeHUh?=
SW756 MoflS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\5dGlEPTB;MD6xOFAzPCBizszN MnqwV2FPT0WU
CTV-1 NGjUU2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVXkN3UzUUN3ME2wMlE3Ozl6IDFOwG0> MXvTRW5ITVJ?
HSC-4 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vqZWlEPTB;MD6xO|E2QCBizszN Mlj6V2FPT0WU
LAMA-84 M2q3Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1mydGlEPTB;MD6yPFY3PCBizszN NVfx[WZiW0GQR1XS
KU812 M1yxbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TDRWlEPTB;MD6zOFA3QCBizszN MUPTRW5ITVJ?
HCC1806 NFT0[5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlHsTWM2OD1yLkO1NlE3KCEQvF2= MoLhV2FPT0WU
DOK NX76e29uT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmfCTWM2OD1yLkO3O|g3KCEQvF2= NWXN[49pW0GQR1XS
NCI-H209 NVv5c|dLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1P2T2lEPTB;MD60NFgxQCBizszN NGXXS2hUSU6JRWK=
EoL-1-cell M4\MO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPBVJdKSzVyPUCuOFE2PzZiIN88US=> M2\hS3NCVkeHUh?=
H9 Mly5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXsTXFiUUN3ME2wMlQ{PDZ2IDFOwG0> NWXOb4tnW0GQR1XS
EM-2 MlzsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjCTWM2OD1yLkSzPFkhKM7:TR?= MlP3V2FPT0WU
NCI-H292 NGfHbFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHLT5E1UUN3ME2wMlQ1OTB6IDFOwG0> NV7CWHhQW0GQR1XS
697 NYXh[2FOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUPJR|UxRTBwNEW2N|MhKM7:TR?= M4XkOnNCVkeHUh?=
BHT-101 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NICwRZBKSzVyPUCuOFY2QSBizszN MX;TRW5ITVJ?
BE-13 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LpR2lEPTB;MD60PFU4OiBizszN MYjTRW5ITVJ?
RS4-11 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV[4coN4UUN3ME2wMlQ5PTh2IDFOwG0> M3v6TXNCVkeHUh?=
IGROV-1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfwcXdKSzVyPUCuOFg4QTdiIN88US=> NU\TRZVbW0GQR1XS
KE-37 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XTUmlEPTB;MD60PVUxQSBizszN NF7RUlRUSU6JRWK=
BV-173 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPsZWNsUUN3ME2wMlUxPzl{IDFOwG0> NEPsXllUSU6JRWK=
MEG-01 M3XE[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnvQTWM2OD1yLkWxNlE1KCEQvF2= NGWw[ppUSU6JRWK=
LB2241-RCC MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXnNHFxUUN3ME2wMlU{PzF6IDFOwG0> NXLDUWhjW0GQR1XS
ACHN M2jXN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPMNZpKSzVyPUCuOVQxPjliIN88US=> NU\QcmYzW0GQR1XS
CTB-1 NGS3bXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUjR[GpoUUN3ME2wMlU1QDJiIN88US=> M2rtTHNCVkeHUh?=
HT-1080 M1fZTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXyxelZ2UUN3ME2wMlU2OzR7IDFOwG0> NGL3[ZhUSU6JRWK=
CHL-1 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmjmTWM2OD1yLkW1OFY2KCEQvF2= NV;iW4NXW0GQR1XS
EW-3 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYT1eJk2UUN3ME2wMlU2QTN3IDFOwG0> M1LvU3NCVkeHUh?=
ES1 NFOzcIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWTJR|UxRTBwNke0PVghKM7:TR?= NXnMcI9iW0GQR1XS
KASUMI-1 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4[0dWlEPTB;MD63NlM{KCEQvF2= NHvaeY5USU6JRWK=
SW13 NYfu[VRGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTTU3MzUUN3ME2wMlc{Pzl6IDFOwG0> MnX5V2FPT0WU
A3-KAW MnrqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHrTWM2OD1yLke5NlA5KCEQvF2= NELHNVdUSU6JRWK=
LB771-HNC MnnzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnH3TWM2OD1yLkizNVA1KCEQvF2= MWrTRW5ITVJ?
OC-314 NH3nfoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTBwOE[5OlUhKM7:TR?= M4rOXXNCVkeHUh?=
MLMA MmHsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{jMbWlEPTB;MD65NFY4PSBizszN Ml\QV2FPT0WU
KARPAS-45 MoWzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVnJR|UxRTBwOUK0OlYhKM7:TR?= M1\F[nNCVkeHUh?=
CAL-27 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHz1VnBKSzVyPUCuPVI6ODZiIN88US=> M1P4c3NCVkeHUh?=
SK-NEP-1 NHvYN49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnyxTWM2OD1yLkm3NlQ5KCEQvF2= MYfTRW5ITVJ?
COR-L105 NX3VRopzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnTZTWM2OD1zLkCwN|k1KCEQvF2= M2\ocXNCVkeHUh?=
TI-73 MoLXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHvmUY5KSzVyPUGuNFE3PSBizszN MonUV2FPT0WU
JVM-3 NVu2dWlZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NY[3NYtsUUN3ME2xMlA2ODF5IDFOwG0> MkfTV2FPT0WU
HAL-01 MlfIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXS5VWZnUUN3ME2xMlA5QDFiIN88US=> MkXMV2FPT0WU
QIMR-WIL NWPTNotKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlqyTWM2OD1zLkC5NFU5KCEQvF2= MljxV2FPT0WU
HSC-3 NHnpbXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlLHTWM2OD1zLkGxO|g{KCEQvF2= MVPTRW5ITVJ?
KY821 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jLemlEPTB;MT6xN|M2OSBizszN NEPmT5dUSU6JRWK=
5637 NVLiV2NFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2TTWmlEPTB;MT6xN|gxOyBizszN NVm4T3J4W0GQR1XS
CAL-33 M2nPfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFLPdYRKSzVyPUGuNVk{ODJiIN88US=> MnrQV2FPT0WU
ES4 NVPSRmRbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTFwMkC3PUAh|ryP MUnTRW5ITVJ?
BHY M1PT[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M135ZmlEPTB;MT6yNlg6OiBizszN MYHTRW5ITVJ?
LB1047-RCC NV;Bb2JST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH\POnhKSzVyPUGuNlM4QDViIN88US=> M{LCU3NCVkeHUh?=
H4 M3KyNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW\JR|UxRTFwMkSyOVUhKM7:TR?= NXfIVmFXW0GQR1XS
RPMI-8866 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXnXelB3UUN3ME2xMlI3OTB4IDFOwG0> M1fQNXNCVkeHUh?=
HO-1-N-1 NX:0doZ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2nNVmlEPTB;MT6yOlM3QSBizszN MXXTRW5ITVJ?
BB30-HNC MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXPJR|UxRTFwMki3NVQhKM7:TR?= MXTTRW5ITVJ?
PC-14 NXHTUFJXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TYTGlEPTB;MT6yPVIxPSBizszN Mm\pV2FPT0WU
NUGC-3 NWPKUFR{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2HJ[WlEPTB;MT6yPVM2PiBizszN Ml7sV2FPT0WU
A4-Fuk MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NELMSotKSzVyPUGuN|A4ODRiIN88US=> NXTleoRPW0GQR1XS
MHH-NB-11 NUjhclN1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{Gx[mlEPTB;MT6zNVM5OyBizszN NVrMXlJrW0GQR1XS
KOSC-2 NXjqZ5BNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTFwM{G3O|UhKM7:TR?= Mn30V2FPT0WU
A498 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXCbXpxUUN3ME2xMlQxOTF|IDFOwG0> NYO1VW5VW0GQR1XS
KG-1 MoPOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTFwNEGyO|MhKM7:TR?= M1iy[HNCVkeHUh?=
DEL MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\CUG5LUUN3ME2xMlQ{PjV5IDFOwG0> NFP5N3VUSU6JRWK=
EW-16 NUfJVXYxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFHLco1KSzVyPUGuOFM6PzNiIN88US=> NVrFT3Q1W0GQR1XS
BPH-1 NIK5VHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvYXmdQUUN3ME2xMlQ1QDB3IDFOwG0> Ml;mV2FPT0WU
JAR NHf0N21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mlv5TWM2OD1zLkS5N|YhKM7:TR?= NGm3VZFUSU6JRWK=
J-RT3-T3-5 MkPXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYHu[Ys6UUN3ME2xMlUyPzJ{IDFOwG0> NX[3OIt6W0GQR1XS
A375 M{fGNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfWOYVUUUN3ME2xMlUyPzd{IDFOwG0> NVjHOGdqW0GQR1XS
SW954 NVnsOIFZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXGxWJY5UUN3ME2xMlU2ODB5IDFOwG0> MoTPV2FPT0WU
Ca9-22 MoOwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2\M[GlEPTB;MT61OlI3KCEQvF2= Mn[1V2FPT0WU
D-566MG NWrSVWpFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTFwNUexOVUhKM7:TR?= MVfTRW5ITVJ?
SCC-15 MkHQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTFwNkG4NFQhKM7:TR?= NUK2OndWW0GQR1XS
HD-MY-Z M13s[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYXJR|UxRTFwNkO1PFQhKM7:TR?= MWjTRW5ITVJ?
HT-1376 NYm2cJFiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWTJR|UxRTFwNkSzOkAh|ryP M1XsZ3NCVkeHUh?=
CAL-54 M4\LTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3XiOWlEPTB;MT62OVcxQSBizszN NIO2UFhUSU6JRWK=
ONS-76 NHzZVpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYPjSZZZUUN3ME2xMlY4PTVzIDFOwG0> MnXqV2FPT0WU
EFO-27 NF3iPI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPwcoxDUUN3ME2xMlY5QTJiIN88US=> NWPX[2lmW0GQR1XS
769-P M{XqO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlXiTWM2OD1zLk[5OVk3KCEQvF2= M4j6fXNCVkeHUh?=
MV-4-11 M2TKXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIX6U|hKSzVyPUGuOlk5PTZiIN88US=> Mn3DV2FPT0WU
NKM-1 NIf6WpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmDOTWM2OD1zLkexPFAzKCEQvF2= M{C0W3NCVkeHUh?=
LOXIMVI M1rBNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTFwN{S1PVkhKM7:TR?= NHnmPIRUSU6JRWK=
KYSE-140 NE\rZnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MW\JR|UxRTFwN{W2OVUhKM7:TR?= MnjyV2FPT0WU
ES5 NXHqZ5dnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{\JT2lEPTB;MT64Olc1PyBizszN M2PYU3NCVkeHUh?=
BB65-RCC NEG4N21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn6wTWM2OD1zLki5PFQ6KCEQvF2= NGLVZXFUSU6JRWK=
HN NGrxfnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVnaR3BJUUN3ME2xMlg6QDd2IDFOwG0> M2DEdXNCVkeHUh?=
A101D NGfrNVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1WyZWlEPTB;MT65N|YzQCBizszN MmnMV2FPT0WU
LoVo NF3rN4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDkVmY2UUN3ME2xMlk4Pjd7IDFOwG0> NVfTWYFjW0GQR1XS
NCI-H526 M3fXO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUfJR|UxRTFwOUmzNlUhKM7:TR?= Ml7kV2FPT0WU
NCI-H1693 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYfZeHV7UUN3ME2xMlk6QDh6IDFOwG0> M4[wN3NCVkeHUh?=
OVCAR-4 NXXqNZlLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWD1bHVXUUN3ME2yMlAxPDN3IDFOwG0> MmLOV2FPT0WU
SK-HEP-1 NG\3Z4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIT6dnFKSzVyPUKuNFA4PDViIN88US=> M1TqbXNCVkeHUh?=
C2BBe1 Ml[3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1rKPWlEPTB;Mj6wN|M4OiBizszN NVTo[4JwW0GQR1XS
MEL-JUSO MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXvJR|UxRTJwMES0OlQhKM7:TR?= NY\WV4duW0GQR1XS
MOLT-16 MoPGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYXLdZZbUUN3ME2yMlA4ODV6IDFOwG0> NXfpSpdMW0GQR1XS
NBsusSR MlPOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWnpcXNPUUN3ME2yMlA6QDh7IDFOwG0> Mki2V2FPT0WU
TK10 NFP5W4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn23TWM2OD1{LkGzOFU5KCEQvF2= NV3hSot4W0GQR1XS
CAL-39 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoH5TWM2OD1{LkG0OFghKM7:TR?= NEDrXYNUSU6JRWK=
NCI-H2030 NFT0U4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnxcGNCUUN3ME2yMlE5QTd|IDFOwG0> M{H1cnNCVkeHUh?=
HCT-116 M2PMfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXKUFJKSzVyPUKuNlI6QDRiIN88US=> NUDQTXhQW0GQR1XS
HTC-C3 NYnkSnd[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVTJR|UxRTJwMk[4NlQhKM7:TR?= NVjQWoN7W0GQR1XS
TYK-nu M3jvSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NY\BW|VCUUN3ME2yMlMxQTB7IDFOwG0> MofHV2FPT0WU
FADU MoLjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTJwM{KyPVYhKM7:TR?= MYjTRW5ITVJ?
A431 M{fYUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M13oTWlEPTB;Mj6zO|AzPSBizszN MlzyV2FPT0WU
TE-11 M2X2Omdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWfJR|UxRTJwM{iwNVkhKM7:TR?= NUG4WmdNW0GQR1XS
CAL-12T MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoXXTWM2OD1{LkSwOFE4KCEQvF2= MVPTRW5ITVJ?
DB M3\vXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlnnTWM2OD1{LkSyPFY6KCEQvF2= NGntWmNUSU6JRWK=
L-363 NEC5fWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml3yTWM2OD1{LkSzOVA4KCEQvF2= NEPoRW9USU6JRWK=
MSTO-211H M{jVVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFrUUWlKSzVyPUKuOlY{QTFiIN88US=> NVPJ[402W0GQR1XS
SK-UT-1 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUXJR|UxRTJwN{G0NFYhKM7:TR?= M1nnenNCVkeHUh?=
RPMI-8226 NGCwV5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH:wdHpKSzVyPUKuO|MyPjRiIN88US=> NXTDbZY4W0GQR1XS
SF295 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnewTWM2OD1{Lke0N|EhKM7:TR?= MUfTRW5ITVJ?
OS-RC-2 M1i1UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFnU[GtKSzVyPUKuO|Y3PzNiIN88US=> MX\TRW5ITVJ?
SK-MEL-24 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3JSXJKSzVyPUKuO|gzOjRiIN88US=> NX3OV5F2W0GQR1XS
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RMG-I MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWjJR|UxRTN|LkSyPFUhKM7:TR?= NEX6Z4JUSU6JRWK=
LU-65 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{KwfWlEPTB;M{SuNVQxQCBizszN M4Cx[nNCVkeHUh?=
GB-1 Mn3QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWDJR|UxRTN3LkC3NlkhKM7:TR?= NGS1e4dUSU6JRWK=
DU-4475 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2T6N2lEPTB;M{WuNVU2OyBizszN NH7XV|FUSU6JRWK=
SBC-5 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlXMTWM2OD1|Nj61PVAzKCEQvF2= M{GybHNCVkeHUh?=
OE33 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjk[GhKSzVyPUO3Mlc2PzdiIN88US=> MVTTRW5ITVJ?
C8166 NFfyUpRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPHTWM2OD1|OD61NlY4KCEQvF2= NFX2N4dUSU6JRWK=
COLO-684 NGfoTGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3LGOmlEPTB;M{iuO|QzQCBizszN M1HqcXNCVkeHUh?=
NCI-H1155 M1fXZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVXJR|UxRTN7LkC0O|EhKM7:TR?= NH31UZpUSU6JRWK=
ATN-1 NWHUdHFkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\rT2lEPTB;M{muO|c6OiBizszN MlHZV2FPT0WU
KARPAS-299 NGiz[WxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mln5TWM2OD1|OT64N|khKM7:TR?= MWnTRW5ITVJ?
KNS-81-FD M3nPcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXfJR|UxRTRyLkO2NFQhKM7:TR?= NF3FcFRUSU6JRWK=
NCI-H1563 M2nDbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHLTWM2OD12MT61NFM6KCEQvF2= MXvTRW5ITVJ?
NB14 NY\nfZdtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{TaRWlEPTB;NEKuO|I3OyBizszN M13scnNCVkeHUh?=
COLO-800 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF3YVGVKSzVyPUSyMlg2OTdiIN88US=> NEPhPFlUSU6JRWK=
MS-1 MnXVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mon5TWM2OD12Mz6wOFg{KCEQvF2= NXnTe|dNW0GQR1XS
OVCAR-8 NXnP[nZqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYC4Sld4UUN3ME20N{43QDB7IDFOwG0> M1nwNHNCVkeHUh?=
SK-PN-DW NW\nWGVDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF:xUo9KSzVyPUSzMlg4PzZiIN88US=> NXLMe|RzW0GQR1XS
G-402 NV;ucGEyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWLJR|UxRTR|LkmwNFYhKM7:TR?= NGPRT4xUSU6JRWK=
NCI-H2291 M2LkWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NICzdlVKSzVyPUS0MlgxOTdiIN88US=> NX[4S3FDW0GQR1XS
PC-3 MlPQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlq4TWM2OD12NT64NFI{KCEQvF2= MVnTRW5ITVJ?
NCI-H1581 M{PmWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTR3Lkm4PFkhKM7:TR?= MXjTRW5ITVJ?
SW1116 NEXiTW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2i4OWlEPTB;NEeuNFE5OiBizszN NY\TS|VWW0GQR1XS
ZR-75-30 NYjkNG12T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTsdZpCUUN3ME20O{4xOjN7IDFOwG0> Mo\rV2FPT0WU
OCI-AML2 M3nqS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo[4TWM2OD12Nz6wPVE5KCEQvF2= NXy3NIhHW0GQR1XS
MDA-MB-231 NIe0UYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHmeZJWUUN3ME20O{43OjR7IDFOwG0> MlKzV2FPT0WU
ES3 NH[yO|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoflTWM2OD12OD6zOVI6KCEQvF2= MoPyV2FPT0WU
NCI-H630 NX;uSm1kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTR7LkG3OFIhKM7:TR?= M2DR[3NCVkeHUh?=
OE19 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml75TWM2OD12OT6yPVAzKCEQvF2= MX3TRW5ITVJ?
NCI-H1573 M1WxPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3rHd2lEPTB;NEmuOlg3OSBizszN NV7iflRxW0GQR1XS
EW-1 Mn7xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmXUTWM2OD12OT65NFg1KCEQvF2= MljjV2FPT0WU

... Click to View More Cell Line Experimental Data

In vivo試験 Bosutinib (60 mg/kg/day) is active against Src-transformed fibroblasts xenografts and HT29 xenografts in nude mice with T/C of 18% and 30%, respectively. [1] Oral administration of Bosutinib for 5 days significantly suppresses K562 tumor growth in mice in a dose-dependent manner, with the large tumors eradicated at dose of 100 mg/kg and tumor free at 150 mg/kg without overt toxicity. [2] As being inactive against Colo205 xenografts in nude mice at 50 mg/kg twice daily, Bosutinib dosing at 75 mg/kg twice daily is necessary against Colo205 xenografts, and increasing the dose of Bosutinib has no additional benefit, in contrast to the significant dose-dependent ability against HT29 xenografts. [4]
臨床試験 A Phase I study to compare the Bosutinib clinical tablet and clinical capsule and to investigate food effect on Bosutinib commercial formulation in healthy subjects has been completed.
特集

プロトコル (参考用のみ)

キナーゼアッセイ:

[1]

The Src and Abl kinase assays The Src kinase activity is measured in an ELISA format. Src (3 units/reaction), reaction buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl2, 0.1 mM EGTA, 0.5 mM Na3VO4) and cdc2 substrate peptide are added to various concentration of Bosutinib and incubated at 30 °C for 10 minutes. The reaction is started by the addition of ATP to a final concentration of 100 μM, incubated at 30 °C for 1 hour and stopped by addition of EDTA. Instructions from the manufacturer are followed for subsequent steps. The Abl kinase assay is performed in a DELFIA solid phase europium-based detection assay format. Biotinylated peptide (2 μM) is bound to streptavidin-coated microtitration plates for 1.5 hours in 1 mg/mL ovalbumin in PBS. The plates are washed for 1 hour with PBS/0.1% Tween 80, followed by a PBS wash. The kinase reaction is incubated for 1 hour at 30°C. Abl kinase (10 units) is mixed with 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 80 μM EGTA, 100 μM ATP, 0.5 mM Na3VO4, 1% DMSO, 1 mM HEPES (pH 7.0), 200 μg/mL ovalbumin and various concentration of Bosutinib. The reaction is stopped with EDTA at a final concentration of 50 mM. The reaction is monitored with Eu-labeled phosphotyrosine antibody and DELFIA enhancement solution.

細胞アッセイ:

[2]

細胞株 Abl-MLV, Rat 2, KU812, K562, and MEG-01 cells
濃度 Dissolved in DMSO, final concentrations ~1 μM
反応時間 72 hours
実験の流れ

Cells are exposed to various concentrations of Bosutinib for 72 hours. Anchorage-independent proliferation of Abl-MLV-transformed fibroblasts is measured in 96-well ultra-low binding plates treated with Sigmacote to block residual cell attachment. Cell proliferation is measured with MTS or Cell-Glo. For the determination of cell cycle or cell death, cells are prepared for FACS analysis in the CycleTest Plus DNA reagent kit and analyzed on a fluorescence-activated cell sorter flow cytometer.

動物実験:

[2]

動物モデル Nude female mice injected with K562 cells
製剤 Suspended in 0.5% methocel/0.4% Tween 80
投薬量 ~150 mg/kg/day
投与方法 Oral 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 Bosutinib (SKI-606) SDF
分子量 530.45
化学式

C26H29Cl2N5O3

CAS No. 380843-75-4
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 100 mg/mL (188.51 mM)
エタノール 2 mg/mL (3.77 mM)
<1 mg/mL (<1 mM)
In vivo 2% DMSO+30% PEG 300+5% Tween 80+ddH2O 10mg/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 4-(2,4-dichloro-5-methoxyphenylamino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

カスタマーフィードバック (3)


Click to enlarge
Rating
Source J Virol, 2011, 85, 2296–2303. Bosutinib (SKI-606) purchased from Selleck
Method Endothelial cell permeability assay
Cell Lines Human endothelial cells
Concentrations 0-10 μM
Incubation Time 15-60 min
Results Figure C defines concentrations of kinase inhibitors which block ANDV-induced EC permeability approximately 50% (IC50s). IC50s of bosutinib are 100 nM and 10 μM. we next assessed the abilities of bosutinib to block ANDV-induced permeability at its IC50s from 15 to 60 min after VEGF addition, we find that bosutinib inhibited ANDV-induced permeability up to 40 to 50% but only at IC50s of 10 μM(Figure D).

Click to enlarge
Rating
Source J Biol Chem, 2010, 285, 7977–7985. Bosutinib (SKI-606) purchased from Selleck
Method Western blot
Cell Lines Mouse sperm
Concentrations 0-50 μM
Incubation Time 60 min
Results In the case of SKI606, a sharp inhibitory effect was observed at 50 μM.

Click to enlarge
Rating
Source Dr. Pablo E.Visconti from University of Massachusetts. Bosutinib (SKI-606) purchased from Selleck
Method Western blot
Cell Lines sperm
Concentrations 50 μΜ
Incubation Time
Results PKA and tyrosine phosphorylation was rescue by Ser/Thr phosphatase inhibitors SKI-606 and SU6656.

文献中の引用 (14)

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