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 M2O1cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvrfVBCUUN3ME2wMlA5OjNzIDFOwG0> NXTBfFI4W0GQR1XS
SW756 NGrBRlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1[ySWlEPTB;MD6xOFAzPCBizszN NILpZ2tUSU6JRWK=
CTV-1 NG\odnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfyTWM2OD1yLkG2N|k5KCEQvF2= MYfTRW5ITVJ?
HSC-4 M{W4Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUDJR|UxRTBwMUexOVghKM7:TR?= NEHLdGVUSU6JRWK=
LAMA-84 NVflRY1tT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2C1XWlEPTB;MD6yPFY3PCBizszN M1TWWHNCVkeHUh?=
KU812 M4S4bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUX5ToF6UUN3ME2wMlM1ODZ6IDFOwG0> NITX[WhUSU6JRWK=
HCC1806 NH7reWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTBwM{WyNVYhKM7:TR?= MkXYV2FPT0WU
DOK M2\0ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUm3bYpDUUN3ME2wMlM4Pzh4IDFOwG0> NH;KcmNUSU6JRWK=
NCI-H209 M2jURWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWj5XZlyUUN3ME2wMlQxQDB6IDFOwG0> NVzYTopyW0GQR1XS
EoL-1-cell NIrtdlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVfJR|UxRTBwNEG1O|YhKM7:TR?= M1LoN3NCVkeHUh?=
H9 NWTOVmw2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3ewN2lEPTB;MD60N|Q3PCBizszN M{HBZ3NCVkeHUh?=
EM-2 Mn;JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3TQdWlEPTB;MD60N|g6KCEQvF2= NYHTeHBMW0GQR1XS
NCI-H292 NVK1XG1WT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVThUFZMUUN3ME2wMlQ1OTB6IDFOwG0> MWDTRW5ITVJ?
697 NVzRbYJ1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYXXWmdvUUN3ME2wMlQ2PjN|IDFOwG0> NH3sZ|RUSU6JRWK=
BHT-101 NFnDbJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWG3UHprUUN3ME2wMlQ3PTliIN88US=> NVP1dHJHW0GQR1XS
BE-13 M3rlbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUDlZmxrUUN3ME2wMlQ5PTd{IDFOwG0> MUfTRW5ITVJ?
RS4-11 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3;MTmlEPTB;MD60PFU5PCBizszN NUjQUY9uW0GQR1XS
IGROV-1 M3HrTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIjZXGdKSzVyPUCuOFg4QTdiIN88US=> MkjPV2FPT0WU
KE-37 M33t[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1O4TmlEPTB;MD60PVUxQSBizszN M1LXPHNCVkeHUh?=
BV-173 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTBwNUC3PVIhKM7:TR?= MYnTRW5ITVJ?
MEG-01 NIizWlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnezTWM2OD1yLkWxNlE1KCEQvF2= MnnPV2FPT0WU
LB2241-RCC NYezO5M{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYThfo1sUUN3ME2wMlU{PzF6IDFOwG0> NHO1eZdUSU6JRWK=
ACHN Ml;3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2DaZmlEPTB;MD61OFA3QSBizszN M3rHPHNCVkeHUh?=
CTB-1 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3HVVWlEPTB;MD61OFgzKCEQvF2= MkLJV2FPT0WU
HT-1080 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFvpdmxKSzVyPUCuOVU{PDliIN88US=> M{i2bHNCVkeHUh?=
CHL-1 NVnZepZOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTBwNUW0OlUhKM7:TR?= MXrTRW5ITVJ?
EW-3 MkfKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnnOTWM2OD1yLkW1PVM2KCEQvF2= NWnVdoRIW0GQR1XS
ES1 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmrwTWM2OD1yLk[3OFk5KCEQvF2= NHXCXm1USU6JRWK=
KASUMI-1 NHTFb|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{TRPWlEPTB;MD63NlM{KCEQvF2= M3z2[3NCVkeHUh?=
SW13 NUTqT4U2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7Xbm5zUUN3ME2wMlc{Pzl6IDFOwG0> NH;FNYVUSU6JRWK=
A3-KAW MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzZO|NKSzVyPUCuO|kzODhiIN88US=> MkDMV2FPT0WU
LB771-HNC NX\FUYpDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2LLemlEPTB;MD64N|ExPCBizszN NHvwPYNUSU6JRWK=
OC-314 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTMTFZKSzVyPUCuPFY6PjViIN88US=> Moe2V2FPT0WU
MLMA NVL1OIt3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;UOmlEPTB;MD65NFY4PSBizszN MX7TRW5ITVJ?
KARPAS-45 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTBwOUK0OlYhKM7:TR?= NITvWYpUSU6JRWK=
CAL-27 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWfVepUyUUN3ME2wMlkzQTB4IDFOwG0> M1Pl[XNCVkeHUh?=
SK-NEP-1 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUXJR|UxRTBwOUeyOFghKM7:TR?= NVO0[4pnW0GQR1XS
COR-L105 M1LLe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXzJR|UxRTFwMECzPVQhKM7:TR?= MWrTRW5ITVJ?
TI-73 M3viV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{fEd2lEPTB;MT6wNVY2KCEQvF2= NXrRTmo6W0GQR1XS
JVM-3 NUXUSnY2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3PUS2lEPTB;MT6wOVAyPyBizszN NU[0TppuW0GQR1XS
HAL-01 M3GxN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MULJR|UxRTFwMEi4NUAh|ryP NYf4XXNtW0GQR1XS
QIMR-WIL MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkS1TWM2OD1zLkC5NFU5KCEQvF2= MorRV2FPT0WU
HSC-3 M1HC[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGi0[5JKSzVyPUGuNVE4QDNiIN88US=> NH3Sb5NUSU6JRWK=
KY821 Mln4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXsPIJKSzVyPUGuNVM{PTFiIN88US=> NYXNRoRlW0GQR1XS
5637 MkPtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLPOosxUUN3ME2xMlE{QDB|IDFOwG0> M3LSNnNCVkeHUh?=
CAL-33 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTFwMUmzNFIhKM7:TR?= NH3y[4VUSU6JRWK=
ES4 MlHXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkG3TWM2OD1zLkKwO|khKM7:TR?= MULTRW5ITVJ?
BHY NWjsNmg6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PDRmlEPTB;MT6yNlg6OiBizszN NVfkcI9IW0GQR1XS
LB1047-RCC MnrnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3WTWM2OD1zLkKzO|g2KCEQvF2= MoPUV2FPT0WU
H4 NVzC[3pNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmTnTWM2OD1zLkK0NlU2KCEQvF2= MkPTV2FPT0WU
RPMI-8866 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGm3cppKSzVyPUGuNlYyODZiIN88US=> MlnNV2FPT0WU
HO-1-N-1 M{LlUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUDJR|UxRTFwMk[zOlkhKM7:TR?= M{L2VXNCVkeHUh?=
BB30-HNC NIKyeVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUPJR|UxRTFwMki3NVQhKM7:TR?= MVvTRW5ITVJ?
PC-14 M2TK[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLv[FZKSzVyPUGuNlkzODViIN88US=> MV3TRW5ITVJ?
NUGC-3 MmTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVjJR|UxRTFwMkmzOVYhKM7:TR?= NXXEUJljW0GQR1XS
A4-Fuk NYTzbnJyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHXcJN{UUN3ME2xMlMxPzB2IDFOwG0> NIGySoNUSU6JRWK=
MHH-NB-11 MmLDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTFwM{GzPFMhKM7:TR?= NHPnbWJUSU6JRWK=
KOSC-2 MkfKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnnpTWM2OD1zLkOxO|c2KCEQvF2= NWO2So4zW0GQR1XS
A498 NWrpdVZET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWnJR|UxRTFwNECxNVMhKM7:TR?= NEfmdnhUSU6JRWK=
KG-1 MkTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M374T2lEPTB;MT60NVI4OyBizszN NEfYU|FUSU6JRWK=
DEL NUTYOFJGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfEeHRKSzVyPUGuOFM3PTdiIN88US=> MXzTRW5ITVJ?
EW-16 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13UbmlEPTB;MT60N|k4OyBizszN M2DNVHNCVkeHUh?=
BPH-1 NHzObWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PIW2lEPTB;MT60OFgxPSBizszN MWTTRW5ITVJ?
JAR M1\NZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nLT2lEPTB;MT60PVM3KCEQvF2= MV3TRW5ITVJ?
J-RT3-T3-5 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LJcWlEPTB;MT61NVczOiBizszN NGLPfHBUSU6JRWK=
A375 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfoUnpKSzVyPUGuOVE4PzJiIN88US=> NFXLRm5USU6JRWK=
SW954 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWfmS215UUN3ME2xMlU2ODB5IDFOwG0> MmK2V2FPT0WU
Ca9-22 NFO3TYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1jneWlEPTB;MT61OlI3KCEQvF2= NXroT2FwW0GQR1XS
D-566MG MmTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXX0UGw3UUN3ME2xMlU4OTV3IDFOwG0> MlfHV2FPT0WU
SCC-15 M2j5[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVjJR|UxRTFwNkG4NFQhKM7:TR?= MmLUV2FPT0WU
HD-MY-Z M4DWemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{fDb2lEPTB;MT62N|U5PCBizszN NEHhT4JUSU6JRWK=
HT-1376 M3;mdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXjJR|UxRTFwNkSzOkAh|ryP MWDTRW5ITVJ?
CAL-54 MmPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDhNnFnUUN3ME2xMlY2PzB7IDFOwG0> Ml;xV2FPT0WU
ONS-76 NHTodGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEDMdJhKSzVyPUGuOlc2PTFiIN88US=> NWC2PHZWW0GQR1XS
EFO-27 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUnJR|UxRTFwNki5NkAh|ryP NFXaV3RUSU6JRWK=
769-P MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoTGTWM2OD1zLk[5OVk3KCEQvF2= M1XjZXNCVkeHUh?=
MV-4-11 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrkS4dKSzVyPUGuOlk5PTZiIN88US=> NIHXd3NUSU6JRWK=
NKM-1 M4LsOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{j3TmlEPTB;MT63NVgxOiBizszN M2izUnNCVkeHUh?=
LOXIMVI MlnHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWfJR|UxRTFwN{S1PVkhKM7:TR?= NWrKTGV6W0GQR1XS
KYSE-140 M13QTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGPxUFZKSzVyPUGuO|U3PTViIN88US=> MnP5V2FPT0WU
ES5 M3viZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnv3TWM2OD1zLki2O|Q4KCEQvF2= NHLmbXpUSU6JRWK=
BB65-RCC NEXKc5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3nOZWlEPTB;MT64PVg1QSBizszN MWnTRW5ITVJ?
HN NGjib29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfVTWM2OD1zLki5PFc1KCEQvF2= MVfTRW5ITVJ?
A101D M1H4XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mln6TWM2OD1zLkmzOlI5KCEQvF2= MVXTRW5ITVJ?
LoVo M1G1WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoHUTWM2OD1zLkm3Olc6KCEQvF2= NWizbpRRW0GQR1XS
NCI-H526 NV\UfFh6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXnJR|UxRTFwOUmzNlUhKM7:TR?= NV7wdYlOW0GQR1XS
NCI-H1693 M{frTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHpTWM2OD1zLkm5PFg5KCEQvF2= MXLTRW5ITVJ?
OVCAR-4 MnnPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW\JR|UxRTJwMEC0N|UhKM7:TR?= NWP3bnh5W0GQR1XS
SK-HEP-1 NHPWdIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIiwWIJKSzVyPUKuNFA4PDViIN88US=> NX;nbYN2W0GQR1XS
C2BBe1 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\GTWM2OD1{LkCzN|czKCEQvF2= MmrFV2FPT0WU
MEL-JUSO NGjWeFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2X6eWlEPTB;Mj6wOFQ3PCBizszN M{X1e3NCVkeHUh?=
MOLT-16 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjDb4dKSzVyPUKuNFcxPThiIN88US=> NVi3dZBwW0GQR1XS
NBsusSR M4fpOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWDJR|UxRTJwMEm4PFkhKM7:TR?= NUPuOpl5W0GQR1XS
TK10 MoH5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlXITWM2OD1{LkGzOFU5KCEQvF2= M2PmTHNCVkeHUh?=
CAL-39 NWDIdmRtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfaZWNsUUN3ME2yMlE1PDhiIN88US=> NWHYR5ltW0GQR1XS
NCI-H2030 MlG1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoT3TWM2OD1{LkG4PVc{KCEQvF2= M3TRcnNCVkeHUh?=
HCT-116 NHPDUVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1nYS2lEPTB;Mj6yNlk5PCBizszN M1LtVnNCVkeHUh?=
HTC-C3 NV[5RotMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTJwMk[4NlQhKM7:TR?= MoDsV2FPT0WU
TYK-nu M{i0Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvHe4h2UUN3ME2yMlMxQTB7IDFOwG0> M{f2XHNCVkeHUh?=
FADU MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEWye5NKSzVyPUKuN|IzQTZiIN88US=> MUPTRW5ITVJ?
A431 NEG1c5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUPJR|UxRTJwM{ewNlUhKM7:TR?= MmrtV2FPT0WU
TE-11 NVHmUGxxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLaUGE3UUN3ME2yMlM5ODF7IDFOwG0> NHn5bnVUSU6JRWK=
CAL-12T MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{\2W2lEPTB;Mj60NFQyPyBizszN M2G3RXNCVkeHUh?=
DB NIXlVIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGfHdmhKSzVyPUKuOFI5PjliIN88US=> M{LvTXNCVkeHUh?=
L-363 NY\MPWt2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{TBcmlEPTB;Mj60N|UxPyBizszN MXvTRW5ITVJ?
MSTO-211H NIfGTGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mny2TWM2OD1{Lk[2N|kyKCEQvF2= M4rmeHNCVkeHUh?=
SK-UT-1 NFyyPYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2TjSWlEPTB;Mj63NVQxPiBizszN NGq0R2ZUSU6JRWK=
RPMI-8226 M33zXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnviTWM2OD1{LkezNVY1KCEQvF2= NX3N[WdMW0GQR1XS
SF295 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrmO5VKSzVyPUKuO|Q{OSBizszN NEDpUIVUSU6JRWK=
OS-RC-2 Ml3KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTKTWM2OD1{Lke2Olc{KCEQvF2= NUeyWpZZW0GQR1XS
SK-MEL-24 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEH0b4xKSzVyPUKuO|gzOjRiIN88US=> NXO3R|FrW0GQR1XS
COR-L23 NYLrWJM3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn7nTWM2OD1{Lke5OFY1KCEQvF2= M{\5SnNCVkeHUh?=
MHH-PREB-1 M3Tnd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV7wepdZUUN3ME2yMlgxOTZzIDFOwG0> NVzselBlW0GQR1XS
SK-N-DZ NV;2dWFOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWmwWZEzUUN3ME2yMlgyPjN6IDFOwG0> MUDTRW5ITVJ?
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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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