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 MkPSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmGyTWM2OD1yLkC4NlMyKCEQvF2= MmLzV2FPT0WU
SW756 NUKy[IlUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MljRTWM2OD1yLkG0NFI1KCEQvF2= MkPnV2FPT0WU
CTV-1 NX7wdlVPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MofGTWM2OD1yLkG2N|k5KCEQvF2= MnexV2FPT0WU
HSC-4 Ml\sS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYfRS2tLUUN3ME2wMlE4OTV6IDFOwG0> NGT2d2hUSU6JRWK=
LAMA-84 NYT5NXZjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVzWOWJ5UUN3ME2wMlI5PjZ2IDFOwG0> NUTHU5A3W0GQR1XS
KU812 NXzvWJFKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2myT2lEPTB;MD6zOFA3QCBizszN NYP1NW1GW0GQR1XS
HCC1806 MnfpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFLIZXpKSzVyPUCuN|UzOTZiIN88US=> M2LRUHNCVkeHUh?=
DOK NGjF[VhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1ryeGlEPTB;MD6zO|c5PiBizszN NIHrW|dUSU6JRWK=
NCI-H209 NXfZN406T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvjTWM2OD1yLkSwPFA5KCEQvF2= NYf0[ZlxW0GQR1XS
EoL-1-cell NYToZYplT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWPJR|UxRTBwNEG1O|YhKM7:TR?= NIft[GxUSU6JRWK=
H9 MmG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoH0TWM2OD1yLkSzOFY1KCEQvF2= Mk\yV2FPT0WU
EM-2 MoXpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFn6ZnZKSzVyPUCuOFM5QSBizszN NYWzU2U3W0GQR1XS
NCI-H292 M13QTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVnJR|UxRTBwNESxNFghKM7:TR?= NHfjWYJUSU6JRWK=
697 NXPGbG9wT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGLIWJVKSzVyPUCuOFU3OzNiIN88US=> NYr2NYdLW0GQR1XS
BHT-101 NFLYbYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fFSmlEPTB;MD60OlU6KCEQvF2= NX\oNos{W0GQR1XS
BE-13 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3S3fmlEPTB;MD60PFU4OiBizszN M2jLNnNCVkeHUh?=
RS4-11 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFPvS5NKSzVyPUCuOFg2QDRiIN88US=> MWXTRW5ITVJ?
IGROV-1 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XDc2lEPTB;MD60PFc6PyBizszN MkDRV2FPT0WU
KE-37 MnvUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXTZnJEUUN3ME2wMlQ6PTB7IDFOwG0> NFXubHFUSU6JRWK=
BV-173 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXXPW5NoUUN3ME2wMlUxPzl{IDFOwG0> MWHTRW5ITVJ?
MEG-01 NHq0NJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\JNmlEPTB;MD61NVIyPCBizszN M4H3dHNCVkeHUh?=
LB2241-RCC NYq4W|h[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPjPJQ3UUN3ME2wMlU{PzF6IDFOwG0> NHvs[2FUSU6JRWK=
ACHN MkHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPrbYt{UUN3ME2wMlU1ODZ7IDFOwG0> M{\JXHNCVkeHUh?=
CTB-1 NFLlWoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4XUdWlEPTB;MD61OFgzKCEQvF2= NGnaW3NUSU6JRWK=
HT-1080 M3P3NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXT6bmhbUUN3ME2wMlU2OzR7IDFOwG0> NFvwNHpUSU6JRWK=
CHL-1 NEOyTXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4C1[2lEPTB;MD61OVQ3PSBizszN NIXoVVBUSU6JRWK=
EW-3 NF;YNnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTBwNUW5N|UhKM7:TR?= NWXZT5FoW0GQR1XS
ES1 NILSTVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkT5TWM2OD1yLk[3OFk5KCEQvF2= NXG4W5RUW0GQR1XS
KASUMI-1 NVLtXIhGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXfJR|UxRTBwN{KzN{Ah|ryP M1zvS3NCVkeHUh?=
SW13 NXLae3p{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4ntbWlEPTB;MD63N|c6QCBizszN MYjTRW5ITVJ?
A3-KAW M2\uT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmL3TWM2OD1yLke5NlA5KCEQvF2= MXTTRW5ITVJ?
LB771-HNC MmDmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlXTTWM2OD1yLkizNVA1KCEQvF2= MnzkV2FPT0WU
OC-314 NX:wdoZxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUTJR|UxRTBwOE[5OlUhKM7:TR?= MlTEV2FPT0WU
MLMA NIrH[G1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnGTG5KSzVyPUCuPVA3PzViIN88US=> NXuzZYpRW0GQR1XS
KARPAS-45 NXW2RVJQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrQdHBnUUN3ME2wMlkzPDZ4IDFOwG0> NX24dpRbW0GQR1XS
CAL-27 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLhTWM2OD1yLkmyPVA3KCEQvF2= MVPTRW5ITVJ?
SK-NEP-1 NV7ZcmNET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoDOTWM2OD1yLkm3NlQ5KCEQvF2= NIWxOZRUSU6JRWK=
COR-L105 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX6wNVFWUUN3ME2xMlAxOzl2IDFOwG0> NX7DUIxWW0GQR1XS
TI-73 NHmxV|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGn2ZlJKSzVyPUGuNFE3PSBizszN NX;VVW44W0GQR1XS
JVM-3 Mo\rS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVPJR|UxRTFwMEWwNVchKM7:TR?= M1zrUXNCVkeHUh?=
HAL-01 NFj4[IVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHqRlhPUUN3ME2xMlA5QDFiIN88US=> NV;sZ4Q6W0GQR1XS
QIMR-WIL MnnOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nVb2lEPTB;MT6wPVA2QCBizszN MYjTRW5ITVJ?
HSC-3 NXfvSZc5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vTUGlEPTB;MT6xNVc5OyBizszN MmPmV2FPT0WU
KY821 NWDqT45kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHNN2hkUUN3ME2xMlE{OzVzIDFOwG0> M1jXe3NCVkeHUh?=
5637 M1XUXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2Phc2lEPTB;MT6xN|gxOyBizszN MXjTRW5ITVJ?
CAL-33 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml3oTWM2OD1zLkG5N|AzKCEQvF2= MVfTRW5ITVJ?
ES4 NYXETpU6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfoTWM2OD1zLkKwO|khKM7:TR?= NG\PW2ZUSU6JRWK=
BHY MoLnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEHvR|NKSzVyPUGuNlI5QTJiIN88US=> NFSzSGNUSU6JRWK=
LB1047-RCC NInYWpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1TofmlEPTB;MT6yN|c5PSBizszN NGOxeXZUSU6JRWK=
H4 NHPVXXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3UdpBKSzVyPUGuNlQzPTViIN88US=> NF72d2NUSU6JRWK=
RPMI-8866 NVnBclZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NILV[HRKSzVyPUGuNlYyODZiIN88US=> MlLlV2FPT0WU
HO-1-N-1 NUSwOFFRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoG1TWM2OD1zLkK2N|Y6KCEQvF2= MoL6V2FPT0WU
BB30-HNC MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3H6WmlEPTB;MT6yPFcyPCBizszN M3\6VHNCVkeHUh?=
PC-14 M2\JZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrES4toUUN3ME2xMlI6OjB3IDFOwG0> M1TnOHNCVkeHUh?=
NUGC-3 M4TSNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVfJR|UxRTFwMkmzOVYhKM7:TR?= MVLTRW5ITVJ?
A4-Fuk MoHDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTFwM{C3NFQhKM7:TR?= MkjKV2FPT0WU
MHH-NB-11 MlrrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLmTWM2OD1zLkOxN|g{KCEQvF2= MljWV2FPT0WU
KOSC-2 NWX5fZMxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnn4TWM2OD1zLkOxO|c2KCEQvF2= NGTzPHRUSU6JRWK=
A498 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkLoTWM2OD1zLkSwNVE{KCEQvF2= MnrBV2FPT0WU
KG-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MW\JR|UxRTFwNEGyO|MhKM7:TR?= MUXTRW5ITVJ?
DEL MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHS0VYRKSzVyPUGuOFM3PTdiIN88US=> M1u3dnNCVkeHUh?=
EW-16 M3TXPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3;ZcWlEPTB;MT60N|k4OyBizszN MWjTRW5ITVJ?
BPH-1 NFW3SVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX3YeHNmUUN3ME2xMlQ1QDB3IDFOwG0> NETVWnBUSU6JRWK=
JAR MnvyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljSTWM2OD1zLkS5N|YhKM7:TR?= MkTvV2FPT0WU
J-RT3-T3-5 NGmyWGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NETQZ|RKSzVyPUGuOVE4OjJiIN88US=> MlTDV2FPT0WU
A375 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\1RWlEPTB;MT61NVc4OiBizszN NWDiWJV6W0GQR1XS
SW954 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIPTO|ZKSzVyPUGuOVUxODdiIN88US=> MVrTRW5ITVJ?
Ca9-22 NWDiclhTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;abHRKSzVyPUGuOVYzPiBizszN NETQTI9USU6JRWK=
D-566MG NFPuRW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTVTWM2OD1zLkW3NVU2KCEQvF2= NEixZYJUSU6JRWK=
SCC-15 MnPOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWHJR|UxRTFwNkG4NFQhKM7:TR?= Mnq4V2FPT0WU
HD-MY-Z M4\aTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTFwNkO1PFQhKM7:TR?= NFTTPZpUSU6JRWK=
HT-1376 MnL1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1qxbmlEPTB;MT62OFM3KCEQvF2= MULTRW5ITVJ?
CAL-54 NGTPWHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fmUWlEPTB;MT62OVcxQSBizszN NEK4SG9USU6JRWK=
ONS-76 NXTTV5JiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmHSTWM2OD1zLk[3OVUyKCEQvF2= MWXTRW5ITVJ?
EFO-27 NHn4[ppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIX1bnpKSzVyPUGuOlg6OiBizszN NXvhO4I1W0GQR1XS
769-P NFe0b2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{H4d2lEPTB;MT62PVU6PiBizszN NWPJdI5mW0GQR1XS
MV-4-11 MoHnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3mxeWlEPTB;MT62PVg2PiBizszN MorqV2FPT0WU
NKM-1 M2\PcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MljnTWM2OD1zLkexPFAzKCEQvF2= NEP3eFBUSU6JRWK=
LOXIMVI NHvLXFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEXTSWxKSzVyPUGuO|Q2QTliIN88US=> M1v0V3NCVkeHUh?=
KYSE-140 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M37OdWlEPTB;MT63OVY2PSBizszN MXHTRW5ITVJ?
ES5 MlXkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEnRXWFKSzVyPUGuPFY4PDdiIN88US=> MmrlV2FPT0WU
BB65-RCC NE\XSY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIfm[ZZKSzVyPUGuPFk5PDliIN88US=> M4\zNHNCVkeHUh?=
HN NY\Kb2NnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXCWYRqUUN3ME2xMlg6QDd2IDFOwG0> NX7sUnJpW0GQR1XS
A101D NYrwOY9zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHS3d|lKSzVyPUGuPVM3OjhiIN88US=> NXfwelhQW0GQR1XS
LoVo M1vxfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7DR5BKSzVyPUGuPVc3PzliIN88US=> M4XBTHNCVkeHUh?=
NCI-H526 M4XB[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1\BPWlEPTB;MT65PVMzPSBizszN MYXTRW5ITVJ?
NCI-H1693 NWrJTWFkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlPLTWM2OD1zLkm5PFg5KCEQvF2= M4nMcnNCVkeHUh?=
OVCAR-4 M37pXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHP3N2VKSzVyPUKuNFA1OzViIN88US=> M1flWnNCVkeHUh?=
SK-HEP-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn\jTWM2OD1{LkCwO|Q2KCEQvF2= M1v6T3NCVkeHUh?=
C2BBe1 NWLMTWJzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHZOllKSzVyPUKuNFM{PzJiIN88US=> NVLwboFKW0GQR1XS
MEL-JUSO NUTrSVFST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIDSSlZKSzVyPUKuNFQ1PjRiIN88US=> MkO1V2FPT0WU
MOLT-16 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlSzTWM2OD1{LkC3NFU5KCEQvF2= MYfTRW5ITVJ?
NBsusSR M1XjWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV;JR|UxRTJwMEm4PFkhKM7:TR?= M3fLb3NCVkeHUh?=
TK10 NEn1fZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVq0NFB{UUN3ME2yMlE{PDV6IDFOwG0> NH\jdnJUSU6JRWK=
CAL-39 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4rJ[2lEPTB;Mj6xOFQ5KCEQvF2= NH\MVXNUSU6JRWK=
NCI-H2030 MmDLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7GVGNTUUN3ME2yMlE5QTd|IDFOwG0> MoPvV2FPT0WU
HCT-116 NIXtb2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4GwVmlEPTB;Mj6yNlk5PCBizszN M4DFNXNCVkeHUh?=
HTC-C3 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlvWTWM2OD1{LkK2PFI1KCEQvF2= MnnvV2FPT0WU
TYK-nu MkiyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXnJR|UxRTJwM{C5NFkhKM7:TR?= NV3UdVROW0GQR1XS
FADU MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTjTWM2OD1{LkOyNlk3KCEQvF2= NFrERYNUSU6JRWK=
A431 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3P0UmlEPTB;Mj6zO|AzPSBizszN Mom1V2FPT0WU
TE-11 MnTZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkTBTWM2OD1{LkO4NFE6KCEQvF2= Mmj0V2FPT0WU
CAL-12T MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVu2dVRvUUN3ME2yMlQxPDF5IDFOwG0> NXzYXm5xW0GQR1XS
DB M3TjUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlTjTWM2OD1{LkSyPFY6KCEQvF2= M3zoZXNCVkeHUh?=
L-363 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkPaTWM2OD1{LkSzOVA4KCEQvF2= MWnTRW5ITVJ?
MSTO-211H NGrVSnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYnsR|B5UUN3ME2yMlY3OzlzIDFOwG0> NWniVWZjW0GQR1XS
SK-UT-1 M2WwXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2jpN2lEPTB;Mj63NVQxPiBizszN NHvCV29USU6JRWK=
RPMI-8226 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUfJR|UxRTJwN{OxOlQhKM7:TR?= M1POcnNCVkeHUh?=
SF295 M2XWbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1T3d2lEPTB;Mj63OFMyKCEQvF2= M3[yOXNCVkeHUh?=
OS-RC-2 NXzTbJRMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\M[2lEPTB;Mj63OlY4OyBizszN M3XkN3NCVkeHUh?=
SK-MEL-24 NULJUI9wT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVLJR|UxRTJwN{iyNlQhKM7:TR?= NHq4bpFUSU6JRWK=
COR-L23 M{O1W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW\JR|UxRTJwN{m0OlQhKM7:TR?= MYjTRW5ITVJ?
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SBC-5 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX7JR|UxRTN4LkW5NFIhKM7:TR?= MX\TRW5ITVJ?
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NCI-H1563 NGPVOVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVHJR|UxRTRzLkWwN|khKM7:TR?= MWDTRW5ITVJ?
NB14 M4X0[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorSTWM2OD12Mj63NlY{KCEQvF2= M2jhS3NCVkeHUh?=
COLO-800 NG[xe2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M37qcWlEPTB;NEKuPFUyPyBizszN MVrTRW5ITVJ?
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SK-PN-DW MoPES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUfJR|UxRTR|Lki3O|YhKM7:TR?= M3m3UXNCVkeHUh?=
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NCI-H2291 M4XVVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHjlU|ZKSzVyPUS0MlgxOTdiIN88US=> MUHTRW5ITVJ?
PC-3 NVe4VXpXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYG1cFlXUUN3ME20OU45ODJ|IDFOwG0> NFTR[lVUSU6JRWK=
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SW1116 M3\zVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmezTWM2OD12Nz6wNVgzKCEQvF2= NWG1[ZY5W0GQR1XS
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ES3 NG\I[WFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTKTWM2OD12OD6zOVI6KCEQvF2= MYnTRW5ITVJ?
NCI-H630 M4[3ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXnJR|UxRTR7LkG3OFIhKM7:TR?= NV\Z[Y5kW0GQR1XS
OE19 M37ZR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUjXOVd4UUN3ME20PU4zQTB{IDFOwG0> MkL5V2FPT0WU
NCI-H1573 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrHbm1KSzVyPUS5MlY5PjFiIN88US=> MVPTRW5ITVJ?
EW-1 NG\pNYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVrJR|UxRTR7LkmwPFQhKM7:TR?= MWLTRW5ITVJ?

... 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 (11)

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