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 M4ricGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH[2b2ZKSzVyPUCuNFgzOzFiIN88US=> NEHDRldUSU6JRWK=
SW756 NYT1fnd2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{TLSGlEPTB;MD6xOFAzPCBizszN M{fjdXNCVkeHUh?=
CTV-1 M3fkXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MofHTWM2OD1yLkG2N|k5KCEQvF2= MX7TRW5ITVJ?
HSC-4 NVHJWXkxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTnT5NFUUN3ME2wMlE4OTV6IDFOwG0> MY\TRW5ITVJ?
LAMA-84 MnnQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXuxc2dIUUN3ME2wMlI5PjZ2IDFOwG0> MY\TRW5ITVJ?
KU812 NGC1R5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NULMXo9UUUN3ME2wMlM1ODZ6IDFOwG0> MYrTRW5ITVJ?
HCC1806 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV7JR|UxRTBwM{WyNVYhKM7:TR?= M{O2e3NCVkeHUh?=
DOK MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnH3TWM2OD1yLkO3O|g3KCEQvF2= MVHTRW5ITVJ?
NCI-H209 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M17INmlEPTB;MD60NFgxQCBizszN MV\TRW5ITVJ?
EoL-1-cell MoHmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnzXTWM2OD1yLkSxOVc3KCEQvF2= M1:wZnNCVkeHUh?=
H9 M4rVbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWnqRlJnUUN3ME2wMlQ{PDZ2IDFOwG0> M2PsTnNCVkeHUh?=
EM-2 NEnJfWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2joNWlEPTB;MD60N|g6KCEQvF2= MlS0V2FPT0WU
NCI-H292 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nwbGlEPTB;MD60OFExQCBizszN NXXmWpprW0GQR1XS
697 NYfEe41nT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHe5R4lKSzVyPUCuOFU3OzNiIN88US=> M{PJbXNCVkeHUh?=
BHT-101 NF;qfJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvBd4dKSzVyPUCuOFY2QSBizszN M1fBcnNCVkeHUh?=
BE-13 NFHRfnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1TRUWlEPTB;MD60PFU4OiBizszN NEPnNZhUSU6JRWK=
RS4-11 NInSO5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnS3TWM2OD1yLkS4OVg1KCEQvF2= M4CwN3NCVkeHUh?=
IGROV-1 M4TNcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWTJR|UxRTBwNEi3PVchKM7:TR?= NYj4OFRnW0GQR1XS
KE-37 M1nCbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkXPTWM2OD1yLkS5OVA6KCEQvF2= MnX6V2FPT0WU
BV-173 NXnUNFVQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTBwNUC3PVIhKM7:TR?= NFPOS2ZUSU6JRWK=
MEG-01 MlnTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE[ydXpKSzVyPUCuOVEzOTRiIN88US=> NUO0VnRqW0GQR1XS
LB2241-RCC M{nSTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXXGN4pvUUN3ME2wMlU{PzF6IDFOwG0> M1vSU3NCVkeHUh?=
ACHN MmHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYe2W|M6UUN3ME2wMlU1ODZ7IDFOwG0> MUfTRW5ITVJ?
CTB-1 NXLGflBMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWS1TVZvUUN3ME2wMlU1QDJiIN88US=> NHLMU4hUSU6JRWK=
HT-1080 M4SyTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojxTWM2OD1yLkW1N|Q6KCEQvF2= M2jRb3NCVkeHUh?=
CHL-1 NIXpVXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX3JR|UxRTBwNUW0OlUhKM7:TR?= M1HDOnNCVkeHUh?=
EW-3 M4nXOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NG\rXVJKSzVyPUCuOVU6OzViIN88US=> MnjRV2FPT0WU
ES1 NIXWNYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV;JR|UxRTBwNke0PVghKM7:TR?= MXfTRW5ITVJ?
KASUMI-1 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Moe2TWM2OD1yLkeyN|MhKM7:TR?= NH\SU29USU6JRWK=
SW13 NHTMTmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrHXVBHUUN3ME2wMlc{Pzl6IDFOwG0> MVvTRW5ITVJ?
A3-KAW Mk[yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFrhU5ZKSzVyPUCuO|kzODhiIN88US=> NF7Fe|JUSU6JRWK=
LB771-HNC MlHTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XGZWlEPTB;MD64N|ExPCBizszN M1jk[HNCVkeHUh?=
OC-314 NXv2RmJpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHl[5lpUUN3ME2wMlg3QTZ3IDFOwG0> MVvTRW5ITVJ?
MLMA NVqw[oF3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3LuWmlEPTB;MD65NFY4PSBizszN MUTTRW5ITVJ?
KARPAS-45 NGC3SWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M130OGlEPTB;MD65NlQ3PiBizszN NXnD[JF3W0GQR1XS
CAL-27 M3jteWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTBwOUK5NFYhKM7:TR?= NXriR2JwW0GQR1XS
SK-NEP-1 M4fVXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\4R5NKSzVyPUCuPVczPDhiIN88US=> NFrCVVhUSU6JRWK=
COR-L105 MoPhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnjoTWM2OD1zLkCwN|k1KCEQvF2= MY\TRW5ITVJ?
TI-73 M3rSemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mli2TWM2OD1zLkCxOlUhKM7:TR?= M4DpWHNCVkeHUh?=
JVM-3 NXjpN4l7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFi4cGlKSzVyPUGuNFUxOTdiIN88US=> MlXpV2FPT0WU
HAL-01 MlS0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXIcoV1UUN3ME2xMlA5QDFiIN88US=> MkPLV2FPT0WU
QIMR-WIL MlvhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2XGVmlEPTB;MT6wPVA2QCBizszN M2\KfHNCVkeHUh?=
HSC-3 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfNTWM2OD1zLkGxO|g{KCEQvF2= M4DMV3NCVkeHUh?=
KY821 Ml7uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFS1TIRKSzVyPUGuNVM{PTFiIN88US=> MoPqV2FPT0WU
5637 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVXxPGxCUUN3ME2xMlE{QDB|IDFOwG0> NWGyNGtqW0GQR1XS
CAL-33 Mm[zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXXJR|UxRTFwMUmzNFIhKM7:TR?= NGTERlZUSU6JRWK=
ES4 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYXH[m5NUUN3ME2xMlIxPzliIN88US=> MYPTRW5ITVJ?
BHY M3G3UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF61cI1KSzVyPUGuNlI5QTJiIN88US=> MonqV2FPT0WU
LB1047-RCC NFjqO|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\rTWM2OD1zLkKzO|g2KCEQvF2= NVXs[ZYzW0GQR1XS
H4 NF7SUmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\LUlJKSzVyPUGuNlQzPTViIN88US=> MnixV2FPT0WU
RPMI-8866 NV:xVYdPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlz4TWM2OD1zLkK2NVA3KCEQvF2= Mlf6V2FPT0WU
HO-1-N-1 NHPTeolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnIb5R3UUN3ME2xMlI3OzZ7IDFOwG0> Mmj1V2FPT0WU
BB30-HNC MljQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoD2TWM2OD1zLkK4O|E1KCEQvF2= MWXTRW5ITVJ?
PC-14 M4H4WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkPLTWM2OD1zLkK5NlA2KCEQvF2= M4fCd3NCVkeHUh?=
NUGC-3 NFS2cm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTFwMkmzOVYhKM7:TR?= M2D2[nNCVkeHUh?=
A4-Fuk MlTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NY\5SplKUUN3ME2xMlMxPzB2IDFOwG0> MkPSV2FPT0WU
MHH-NB-11 M1jwTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGDlN5RKSzVyPUGuN|E{QDNiIN88US=> MWHTRW5ITVJ?
KOSC-2 MkjtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVXlTVFrUUN3ME2xMlMyPzd3IDFOwG0> M4jtXHNCVkeHUh?=
A498 NH[xfYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{LCe2lEPTB;MT60NFEyOyBizszN NUG5fZhWW0GQR1XS
KG-1 M3jyd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWLJOVhSUUN3ME2xMlQyOjd|IDFOwG0> M{CxbnNCVkeHUh?=
DEL NGq1ZZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jINmlEPTB;MT60N|Y2PyBizszN NGDhWIFUSU6JRWK=
EW-16 NWWyXmxpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWDJR|UxRTFwNEO5O|MhKM7:TR?= M{nPS3NCVkeHUh?=
BPH-1 MlP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fXWGlEPTB;MT60OFgxPSBizszN NFz6dVBUSU6JRWK=
JAR MmGzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTFwNEmzOkAh|ryP MWLTRW5ITVJ?
J-RT3-T3-5 M{TK[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYjhN49NUUN3ME2xMlUyPzJ{IDFOwG0> M1j3TXNCVkeHUh?=
A375 M4\tUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIW2[W9KSzVyPUGuOVE4PzJiIN88US=> M4\DOXNCVkeHUh?=
SW954 NYfoOpR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYfJR|UxRTFwNUWwNFchKM7:TR?= MXvTRW5ITVJ?
Ca9-22 NEmzUoxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17FV2lEPTB;MT61OlI3KCEQvF2= MXnTRW5ITVJ?
D-566MG Ml7RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVPWVWgxUUN3ME2xMlU4OTV3IDFOwG0> Mn7rV2FPT0WU
SCC-15 M3fkTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnr[2VKSzVyPUGuOlE5ODRiIN88US=> NVO3XlB6W0GQR1XS
HD-MY-Z M3fGSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mln5TWM2OD1zLk[zOVg1KCEQvF2= NWXWN|NLW0GQR1XS
HT-1376 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml;LTWM2OD1zLk[0N|YhKM7:TR?= Mlq3V2FPT0WU
CAL-54 MmqxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{HD[WlEPTB;MT62OVcxQSBizszN NEm2WXlUSU6JRWK=
ONS-76 NFvUU5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHO1S3ZKSzVyPUGuOlc2PTFiIN88US=> NHTtRVJUSU6JRWK=
EFO-27 M2S3OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF3XOJFKSzVyPUGuOlg6OiBizszN NVXxR3dzW0GQR1XS
769-P M{Xafmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX\JR|UxRTFwNkm1PVYhKM7:TR?= NFr0NJhUSU6JRWK=
MV-4-11 NGD1OlBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkS2TWM2OD1zLk[5PFU3KCEQvF2= M1PvTXNCVkeHUh?=
NKM-1 MkLIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWjQ[44yUUN3ME2xMlcyQDB{IDFOwG0> NXzRSI85W0GQR1XS
LOXIMVI M2\ROWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTFwN{S1PVkhKM7:TR?= NYnv[XJIW0GQR1XS
KYSE-140 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXrJR|UxRTFwN{W2OVUhKM7:TR?= NWCwVlA4W0GQR1XS
ES5 M1HV[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo\aTWM2OD1zLki2O|Q4KCEQvF2= MXTTRW5ITVJ?
BB65-RCC MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUT6b4JEUUN3ME2xMlg6QDR7IDFOwG0> MUHTRW5ITVJ?
HN MonVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLLO5JKSzVyPUGuPFk5PzRiIN88US=> NYPNT4ExW0GQR1XS
A101D M1f1UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHrYcHdKSzVyPUGuPVM3OjhiIN88US=> Mn7iV2FPT0WU
LoVo MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUfubnNQUUN3ME2xMlk4Pjd7IDFOwG0> NWm0e2lzW0GQR1XS
NCI-H526 M3vKTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTFwOUmzNlUhKM7:TR?= M1TiW3NCVkeHUh?=
NCI-H1693 MnfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTFwOUm4PFghKM7:TR?= MX7TRW5ITVJ?
OVCAR-4 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHYboM3UUN3ME2yMlAxPDN3IDFOwG0> NV7peGVtW0GQR1XS
SK-HEP-1 M4PySWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVfJR|UxRTJwMEC3OFUhKM7:TR?= M2rFNnNCVkeHUh?=
C2BBe1 MlPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLw[2ZRUUN3ME2yMlA{Ozd{IDFOwG0> Mlf2V2FPT0WU
MEL-JUSO MmnHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXTXeVlSUUN3ME2yMlA1PDZ2IDFOwG0> MYnTRW5ITVJ?
MOLT-16 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3qwSWlEPTB;Mj6wO|A2QCBizszN NEXQb2pUSU6JRWK=
NBsusSR M3jxNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTJwMEm4PFkhKM7:TR?= MlS3V2FPT0WU
TK10 NWmwWWlsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXqwSnA2UUN3ME2yMlE{PDV6IDFOwG0> M{nJd3NCVkeHUh?=
CAL-39 NIm0VYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLLSoFKSzVyPUKuNVQ1QCBizszN MnOwV2FPT0WU
NCI-H2030 M1;ReWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonTTWM2OD1{LkG4PVc{KCEQvF2= M2TPXXNCVkeHUh?=
HCT-116 NWS0dmtmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MU\JR|UxRTJwMkK5PFQhKM7:TR?= M{GwNHNCVkeHUh?=
HTC-C3 M4G1[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Moj4TWM2OD1{LkK2PFI1KCEQvF2= M1fhbXNCVkeHUh?=
TYK-nu MnnXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4rzOGlEPTB;Mj6zNFkxQSBizszN MmLtV2FPT0WU
FADU NV;sWFJ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\6dmlEPTB;Mj6zNlI6PiBizszN NFXzcGJUSU6JRWK=
A431 MknwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmS4TWM2OD1{LkO3NFI2KCEQvF2= Mo\aV2FPT0WU
TE-11 M2XPPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjKZ5JKSzVyPUKuN|gxOTliIN88US=> M1POW3NCVkeHUh?=
CAL-12T NWX2OXRyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVXJR|UxRTJwNEC0NVchKM7:TR?= M{fSfHNCVkeHUh?=
DB NWD1OYVkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUj2ZnZWUUN3ME2yMlQzQDZ7IDFOwG0> NIK1UHJUSU6JRWK=
L-363 NH2zZ3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{jhO2lEPTB;Mj60N|UxPyBizszN MlHSV2FPT0WU
MSTO-211H MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrSUWlKSzVyPUKuOlY{QTFiIN88US=> Mlm0V2FPT0WU
SK-UT-1 MnjQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWfJR|UxRTJwN{G0NFYhKM7:TR?= Mlj5V2FPT0WU
RPMI-8226 NITnNHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmnsTWM2OD1{LkezNVY1KCEQvF2= MnHPV2FPT0WU
SF295 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH;rbGxKSzVyPUKuO|Q{OSBizszN M4LSVXNCVkeHUh?=
OS-RC-2 MlznS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUflb2hjUUN3ME2yMlc3Pjd|IDFOwG0> NHu3dllUSU6JRWK=
SK-MEL-24 MkT4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYPLfoo5UUN3ME2yMlc5OjJ2IDFOwG0> MoTkV2FPT0WU
COR-L23 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPaTWM2OD1{Lke5OFY1KCEQvF2= M2fTXHNCVkeHUh?=
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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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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