Bosutinib (SKI-606) 化学構造
分子量: 530.45

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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 M37oUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXXONJJWUUN3ME2wMlA5OjNzIDFOwG0> MVXTRW5ITVJ?
SW756 M4fNZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2fKbmlEPTB;MD6xOFAzPCBizszN MmrtV2FPT0WU
CTV-1 NVfKU25pT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDZSnRKSzVyPUCuNVY{QThiIN88US=> MnfCV2FPT0WU
HSC-4 NY\rSY4yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfMUY9zUUN3ME2wMlE4OTV6IDFOwG0> M{i5[3NCVkeHUh?=
LAMA-84 M3X3N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3Lp[WlEPTB;MD6yPFY3PCBizszN NY\sXXdGW0GQR1XS
KU812 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEPaeo1KSzVyPUCuN|QxPjhiIN88US=> NWSwcnlIW0GQR1XS
HCC1806 MkDWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU\JR|UxRTBwM{WyNVYhKM7:TR?= MVPTRW5ITVJ?
DOK MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUOzbWtwUUN3ME2wMlM4Pzh4IDFOwG0> M2rGbnNCVkeHUh?=
NCI-H209 MlzrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\BPWduUUN3ME2wMlQxQDB6IDFOwG0> NUDzW2hOW0GQR1XS
EoL-1-cell M1rsOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTBwNEG1O|YhKM7:TR?= NV20S3lKW0GQR1XS
H9 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jSW2lEPTB;MD60N|Q3PCBizszN MnXzV2FPT0WU
EM-2 Mn7vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTBwNEO4PUAh|ryP NH7SZldUSU6JRWK=
NCI-H292 NUW1XGYzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{HteGlEPTB;MD60OFExQCBizszN MYfTRW5ITVJ?
697 NEXyN4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTBwNEW2N|MhKM7:TR?= NV[3elV3W0GQR1XS
BHT-101 Mn\5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjwWWRHUUN3ME2wMlQ3PTliIN88US=> NWDQ[HdxW0GQR1XS
BE-13 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTBwNEi1O|IhKM7:TR?= MmnvV2FPT0WU
RS4-11 NHGwfm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\4TWM2OD1yLkS4OVg1KCEQvF2= NHn6NZlUSU6JRWK=
IGROV-1 MmHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1vOcGlEPTB;MD60PFc6PyBizszN NYj4OIp{W0GQR1XS
KE-37 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTBwNEm1NFkhKM7:TR?= MYLTRW5ITVJ?
BV-173 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXnJR|UxRTBwNUC3PVIhKM7:TR?= M2fqPHNCVkeHUh?=
MEG-01 NFLJO3lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4HCfmlEPTB;MD61NVIyPCBizszN MUjTRW5ITVJ?
LB2241-RCC M3LJeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWDJR|UxRTBwNUO3NVghKM7:TR?= NFHlbYtUSU6JRWK=
ACHN MkLxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEHTb5BKSzVyPUCuOVQxPjliIN88US=> NGDPfZFUSU6JRWK=
CTB-1 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPJTWM2OD1yLkW0PFIhKM7:TR?= M3jkR3NCVkeHUh?=
HT-1080 M4jxRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUDJR|UxRTBwNUWzOFkhKM7:TR?= MY\TRW5ITVJ?
CHL-1 M2PmR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUGzOGdXUUN3ME2wMlU2PDZ3IDFOwG0> NIjq[mpUSU6JRWK=
EW-3 NEPheJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MofUTWM2OD1yLkW1PVM2KCEQvF2= NYPT[XVlW0GQR1XS
ES1 M2TPVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVPDXnpUUUN3ME2wMlY4PDl6IDFOwG0> NF\HVGVUSU6JRWK=
KASUMI-1 M3XxRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTBwN{KzN{Ah|ryP MWXTRW5ITVJ?
SW13 NH3IfJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWfJR|UxRTBwN{O3PVghKM7:TR?= NXfyfGcyW0GQR1XS
A3-KAW M2PGWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XJcmlEPTB;MD63PVIxQCBizszN NXr4cVZJW0GQR1XS
LB771-HNC NXzPTYRbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmLYTWM2OD1yLkizNVA1KCEQvF2= MYnTRW5ITVJ?
OC-314 NEexXmtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvqWpJiUUN3ME2wMlg3QTZ3IDFOwG0> NWPGcmY6W0GQR1XS
MLMA MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXLJR|UxRTBwOUC2O|UhKM7:TR?= MV\TRW5ITVJ?
KARPAS-45 M2rmNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWjJR|UxRTBwOUK0OlYhKM7:TR?= MnmxV2FPT0WU
CAL-27 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGrjUHFKSzVyPUCuPVI6ODZiIN88US=> NVzCdpdsW0GQR1XS
SK-NEP-1 M1vOUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWXiPIZ[UUN3ME2wMlk4OjR6IDFOwG0> M4DNW3NCVkeHUh?=
COR-L105 NHfENI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXe2cVZtUUN3ME2xMlAxOzl2IDFOwG0> M4T1O3NCVkeHUh?=
TI-73 NYWw[Jo{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfUZoxKSzVyPUGuNFE3PSBizszN NETX[XdUSU6JRWK=
JVM-3 M2T4PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rUZWlEPTB;MT6wOVAyPyBizszN NWHIPJhtW0GQR1XS
HAL-01 NV3KTFRET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEeyb|hKSzVyPUGuNFg5OSBizszN MVvTRW5ITVJ?
QIMR-WIL NH7Ee29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTFwMEmwOVghKM7:TR?= M4LWd3NCVkeHUh?=
HSC-3 Mmq1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fxeGlEPTB;MT6xNVc5OyBizszN NWO4OVZwW0GQR1XS
KY821 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTFwMUOzOVEhKM7:TR?= Ml3SV2FPT0WU
5637 MnnNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoLTTWM2OD1zLkGzPFA{KCEQvF2= MX3TRW5ITVJ?
CAL-33 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHQRpBKSzVyPUGuNVk{ODJiIN88US=> MV3TRW5ITVJ?
ES4 MnTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfCdVZFUUN3ME2xMlIxPzliIN88US=> MXLTRW5ITVJ?
BHY NGnyPWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlroTWM2OD1zLkKyPFkzKCEQvF2= M4f5enNCVkeHUh?=
LB1047-RCC NX[1W3ZjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFrycpdKSzVyPUGuNlM4QDViIN88US=> NUnlNGtpW0GQR1XS
H4 NYDhb2RST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4\EZmlEPTB;MT6yOFI2PSBizszN NFrKeHFUSU6JRWK=
RPMI-8866 MoGxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljKTWM2OD1zLkK2NVA3KCEQvF2= NGLvNIRUSU6JRWK=
HO-1-N-1 NI[4XoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PsTmlEPTB;MT6yOlM3QSBizszN NH7KVplUSU6JRWK=
BB30-HNC NVi4eXdXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVLJR|UxRTFwMki3NVQhKM7:TR?= MoG3V2FPT0WU
PC-14 NWP2OVFoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3H0bmlEPTB;MT6yPVIxPSBizszN M4rYTHNCVkeHUh?=
NUGC-3 MlO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkCwTWM2OD1zLkK5N|U3KCEQvF2= MWXTRW5ITVJ?
A4-Fuk NFPIeotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2TtTGlEPTB;MT6zNFcxPCBizszN MWfTRW5ITVJ?
MHH-NB-11 M4HaSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4nHWWlEPTB;MT6zNVM5OyBizszN NI\x[o1USU6JRWK=
KOSC-2 M{jhT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWnIeZRuUUN3ME2xMlMyPzd3IDFOwG0> NWrYN5J2W0GQR1XS
A498 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVmwNIk6UUN3ME2xMlQxOTF|IDFOwG0> MUjTRW5ITVJ?
KG-1 NF;HSVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXjJR|UxRTFwNEGyO|MhKM7:TR?= NXnGOHBbW0GQR1XS
DEL M1uxTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo\FTWM2OD1zLkSzOlU4KCEQvF2= M1z0[HNCVkeHUh?=
EW-16 M1XyfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3:3OGlEPTB;MT60N|k4OyBizszN M2mwd3NCVkeHUh?=
BPH-1 NYnCTGlRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXjwZmE6UUN3ME2xMlQ1QDB3IDFOwG0> NIDYXJpUSU6JRWK=
JAR M4i0bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mlv1TWM2OD1zLkS5N|YhKM7:TR?= MmL2V2FPT0WU
J-RT3-T3-5 M4PvW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTFwNUG3NlIhKM7:TR?= NVu3XVRnW0GQR1XS
A375 MlvOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPJ[XdiUUN3ME2xMlUyPzd{IDFOwG0> MUTTRW5ITVJ?
SW954 NWOwV2QzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{niRWlEPTB;MT61OVAxPyBizszN MY\TRW5ITVJ?
Ca9-22 NGPMUldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1nRd2lEPTB;MT61OlI3KCEQvF2= NFi3Z|BUSU6JRWK=
D-566MG MnvvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIKzfI1KSzVyPUGuOVcyPTViIN88US=> NWHMdFhOW0GQR1XS
SCC-15 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEW4TmZKSzVyPUGuOlE5ODRiIN88US=> MkC1V2FPT0WU
HD-MY-Z NH7QS5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWHrV3E2UUN3ME2xMlY{PTh2IDFOwG0> MmDlV2FPT0WU
HT-1376 NGHleYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGHDPVFKSzVyPUGuOlQ{PiBizszN NFfhTIJUSU6JRWK=
CAL-54 M4jxVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPjb3JKSzVyPUGuOlU4ODliIN88US=> M4Xr[3NCVkeHUh?=
ONS-76 NUW5N4k6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHJNI1OUUN3ME2xMlY4PTVzIDFOwG0> NVPrWJY2W0GQR1XS
EFO-27 M3LJbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7CcJJKSzVyPUGuOlg6OiBizszN M2ToU3NCVkeHUh?=
769-P NYPSTnlXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\BU2lEPTB;MT62PVU6PiBizszN MUDTRW5ITVJ?
MV-4-11 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIPzTJlKSzVyPUGuOlk5PTZiIN88US=> NVfPU2d7W0GQR1XS
NKM-1 M1fNb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYfJR|UxRTFwN{G4NFIhKM7:TR?= MV3TRW5ITVJ?
LOXIMVI MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LYW2lEPTB;MT63OFU6QSBizszN MmPYV2FPT0WU
KYSE-140 M4XWbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGXrTFZKSzVyPUGuO|U3PTViIN88US=> NXfHNll1W0GQR1XS
ES5 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3jYdWlEPTB;MT64Olc1PyBizszN MY\TRW5ITVJ?
BB65-RCC M4jX[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\uXWlEPTB;MT64PVg1QSBizszN NHqwW3RUSU6JRWK=
HN NIi5SYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1z2XmlEPTB;MT64PVg4PCBizszN MWDTRW5ITVJ?
A101D NGT4TohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{DObWlEPTB;MT65N|YzQCBizszN MXHTRW5ITVJ?
LoVo M1;IT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF35XWVKSzVyPUGuPVc3PzliIN88US=> MX;TRW5ITVJ?
NCI-H526 NWKyTZVvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoPYTWM2OD1zLkm5N|I2KCEQvF2= MVzTRW5ITVJ?
NCI-H1693 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDEWphKSzVyPUGuPVk5QDhiIN88US=> M4Xke3NCVkeHUh?=
OVCAR-4 NX;rOHdUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2XsXmlEPTB;Mj6wNFQ{PSBizszN M1PJ[HNCVkeHUh?=
SK-HEP-1 NVLBZ4l{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2nT[mlEPTB;Mj6wNFc1PSBizszN NHj0PFBUSU6JRWK=
C2BBe1 NWDXeZlNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TBSmlEPTB;Mj6wN|M4OiBizszN M3vvcXNCVkeHUh?=
MEL-JUSO M3HaNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH;C[5dKSzVyPUKuNFQ1PjRiIN88US=> NF7FWYRUSU6JRWK=
MOLT-16 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;jeWlEPTB;Mj6wO|A2QCBizszN NHTLV3dUSU6JRWK=
NBsusSR NX7ZeJlET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDMTIpCUUN3ME2yMlA6QDh7IDFOwG0> MoDwV2FPT0WU
TK10 M3LDNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYC4RnRYUUN3ME2yMlE{PDV6IDFOwG0> MkH4V2FPT0WU
CAL-39 NIHF[o5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXHTWM2OD1{LkG0OFghKM7:TR?= MknRV2FPT0WU
NCI-H2030 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MojrTWM2OD1{LkG4PVc{KCEQvF2= M13pVHNCVkeHUh?=
HCT-116 MmruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jsbmlEPTB;Mj6yNlk5PCBizszN MX;TRW5ITVJ?
HTC-C3 M13aUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGXMdWxKSzVyPUKuNlY5OjRiIN88US=> NEPyOYdUSU6JRWK=
TYK-nu MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXS2co12UUN3ME2yMlMxQTB7IDFOwG0> M1fXTXNCVkeHUh?=
FADU MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF[0NGpKSzVyPUKuN|IzQTZiIN88US=> M4XoTnNCVkeHUh?=
A431 Ml7mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\yTWM2OD1{LkO3NFI2KCEQvF2= NIfLVJVUSU6JRWK=
TE-11 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmHnTWM2OD1{LkO4NFE6KCEQvF2= MlTBV2FPT0WU
CAL-12T NIm5e2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHnNWJNKSzVyPUKuOFA1OTdiIN88US=> MW\TRW5ITVJ?
DB NYqxeZBXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV7vb|NWUUN3ME2yMlQzQDZ7IDFOwG0> M4rydHNCVkeHUh?=
L-363 NH\jVHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4\PZmlEPTB;Mj60N|UxPyBizszN NVHEWll2W0GQR1XS
MSTO-211H MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3TNUGlEPTB;Mj62OlM6OSBizszN M4XxSnNCVkeHUh?=
SK-UT-1 M37rPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTJwN{G0NFYhKM7:TR?= NXLx[ZJmW0GQR1XS
RPMI-8226 NW\RfpY5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M121PGlEPTB;Mj63N|E3PCBizszN NF7uWGpUSU6JRWK=
SF295 NF;sbYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPaTWM2OD1{Lke0N|EhKM7:TR?= M3zDNHNCVkeHUh?=
OS-RC-2 Mmn4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3aTWM2OD1{Lke2Olc{KCEQvF2= Mor0V2FPT0WU
SK-MEL-24 M{DUNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\6e2h6UUN3ME2yMlc5OjJ2IDFOwG0> NUjDb29[W0GQR1XS
COR-L23 MlrXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7ySWNKSzVyPUKuO|k1PjRiIN88US=> M{\ob3NCVkeHUh?=
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... 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)
* <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 (11)

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