Alisertib (MLN8237) 化学構造
分子量: 518.92

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Quality Control & MSDS

製品説明

  • Compare Aurora Kinase Inhibitors
    Aurora Kinase製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 Alisertib (MLN8237)は、1.2nMのIC50による選択的なオーロラA阻害剤です。
ターゲット Aurora A
IC50 1.2 nM [1]
In vitro試験 MLN8237 shows >200-fold higher selectivity for Aurora A than the structurally related Aurora B with an IC50 of 396.5 nM, and does not have any significant activity against 205 other kinases. [1] MLN8237 (0.5 μM) treatment inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. MLN8237 significantly inhibits cell proliferation in multiple myeloma (MM) cell lines with IC50 values of 0.003-1.71 μM. MLN8237 displays more potent anti-proliferation activity against primary MM cells and MM cell lines in the presence of BM stroma cells, as well as IL-6 and IGF-1 than against MM cells alone. MLN8237 (0.5 μM) induces 2- to 6-fold increase in G2/M phase in primary MM cells and cell lines, as well as significant apoptosis and senescence, involving the up-regulation of p53, p21 and p27, as well as PARP, caspase 3, and caspase 9 cleavage. In addition, MLN8237 shows strong synergistic anti-MM effect with dexamethasone, as well as additive effect with doxorubicin and bortezomib. [2] MLN8237 (0.5 μM) treatment causes the inhibition of colony formation of FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, and induces a significant increase in the percentage of polyploid cells, and subsequently an increase in the percentage of cells in the sub-G1 phase, which can be further enhanced in combination with cisplatin (2.5 μM), involving the higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP as compared with a single-agent treatment. [3]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
HCT116 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrpXmsxNjVizszN NGPXOGI4OiCq Mnv4SG1UVw>? M4e3dGlEPTB;MD6wOEDPxE1? MXqyOlE{PjZ6NB?=
LS174T M2DLfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYqwMlUh|ryP NXzER21sPzJiaB?= MYLEUXNQ NGOwTXZKSzVyPUCuNFUh|ryP NVW0[29kOjZzM{[2PFQ>
T84 NEL6eYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rNelAvPSEQvF2= Mn7OO|IhcA>? NYjWXW4yTE2VTx?= MmX5TWM2OD1yLkC5JO69VQ>? MUGyOlE{PjZ6NB?=
LS180 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrWUWwxNjVizszN MkS3O|IhcA>? NWTxV2lLTE2VTx?= M1vBS2lEPTB;MTFOwG0> NEDhZYczPjF|Nk[4OC=>
SW948 MnjwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVKwMlUh|ryP NHy1ZZg4OiCq MnnzSG1UVw>? NXvr[XB5UUN3ME2xJO69VQ>? NYn0N2NDOjZzM{[2PFQ>
HCT15 NIi2NldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVGwMlUh|ryP M3nySlczKGh? MW\EUXNQ MVTJR|UxRDBwNDFOwG0> MmrBNlYyOzZ4OES=
DLD-1 NHjMbFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2LnVVAvPSEQvF2= M1e5dFczKGh? NFHkXFBFVVOR MVrJR|UxRDBwODFOwG0> M1i4PFI3OTN4Nki0
MIP-101 M2rCW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{DUdlAvPSEQvF2= MnXVO|IhcA>? MVjEUXNQ NGLFVnNKSzVyPUGg{txO NU\CV2VSOjZzM{[2PFQ>
SNU1544 MkLhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mon5NE42KM7:TR?= NEjmWYo4OiCq MkXSSG1UVw>? MlHYTWM2OD1zIN88US=> NGHWVFIzPjF|Nk[4OC=>
OCI-Ly10 M2Xle2N6fG:2b4jpZ{BCe3OjeR?= NU\Bd5BtPzJiaB?= M3XIfmROW09? MVLJR|UxRTBwMEW4JO69VQ>? M1L5blI2QDd6M{Ox
SU-DHL2 MXnDfZRwfG:6aXOgRZN{[Xl? Mk\iO|IhcA>? Ml7ySG1UVw>? NXTLdHN7UUN3ME2wMlAyKM7:TR?= MmiwNlU5Pzh|M{G=
OCI-LY7 M4HGZWN6fG:2b4jpZ{BCe3OjeR?= NXPhd2Z1PzJiaB?= MoTtSG1UVw>? MmPNTWM2OD1yLkC4NUDPxE1? NFT3N4IzPTh5OEOzNS=>
SU-DHL6 MWrDfZRwfG:6aXOgRZN{[Xl? NXXOXllpPzJiaB?= M2P4bGROW09? NHzY[mdKSzVyPUCuOFgzKM7:TR?= NGPm[2QzPTh5OEOzNS=>
Jeko-1 NI\zR4REgXSxdH;4bYMhSXO|YYm= Mln3O|IhcA>? M365W2ROW09? NFznWGZKSzVyPUCuNFI6KM7:TR?= NHTmeVYzPTh5OEOzNS=>
JVM-2 M4XRUGN6fG:2b4jpZ{BCe3OjeR?= MYm3NkBp MlLmSG1UVw>? NFrIdFhKSzVyPUCuNFEh|ryP MWGyOVg4QDN|MR?=
Rec-1 M1TGbmN6fG:2b4jpZ{BCe3OjeR?= NGHDWms4OiCq NGP3NoFFVVOR NF7vTVdKSzVyPUCuNFg4KM7:TR?= M2\mRlI2QDd6M{Ox
Z-138 NUOyVXl1S3m2b4TvfIlkKEG|c3H5 M2rrTlczKGh? NFqyVXdFVVOR NYPkXoRbUUN3ME2wMlAyOyEQvF2= NYfs[XZDOjV6N{izN|E>
H9 NGj0cpVEgXSxdH;4bYMhSXO|YYm= NFvpNok4OiCq M1rGZ2ROW09? NVX6fpRHUUN3ME2wMlYh|ryP NWPmSoVDOjV6N{izN|E>
HH M3TUc2N6fG:2b4jpZ{BCe3OjeR?= NUHRS2x3PzJiaB?= NF;WdmRFVVOR NGHUUJBKSzVyPUCuO{DPxE1? NYezZ2tkOjV6N{izN|E>
DND41 NEL6dI1EgXSxdH;4bYMhSXO|YYm= M1e3SVczKGh? NHS2bWtFVVOR Ml7iTWM2OD1yLkGg{txO MV[yOVg4QDN|MR?=
CCL119 M1Xvd2N6fG:2b4jpZ{BCe3OjeR?= NGXmTJc4OiCq Mn[2SG1UVw>? NX\vc5BJUUN3ME2wMlA3OiEQvF2= M2Dy[lI2QDd6M{Ox
J.Cam 1.6 NWr5e4dtS3m2b4TvfIlkKEG|c3H5 M4fZelczKGh? MWXEUXNQ NEPUcIhKSzVyPUCuNVA2KM7:TR?= NFnzfWszPTh5OEOzNS=>
Sup-T1 Mk\1R5l1d3SxeHnjJGF{e2G7 M{OxblczKGh? NHHtOXJFVVOR MnPxTWM2OD1{LkG0NkDPxE1? MkjuNlU5Pzh|M{G=
Tib 152 MUPDfZRwfG:6aXOgRZN{[Xl? NV;MVZR5PzJiaB?= NXnUfplsTE2VTx?= NFLNTIlKSzVyPUCuPEDPxE1? NHuyNW8zPTh5OEOzNS=>
MCF7 NWrXPYtuTnWwY4Tpc44hSXO|YYm= NXHxToJLPSEQvF2= NGHEcGMzPCCq NHflNG5FVVOR MULJcoR2[2W|IFeyM20h[XK{ZYP0 M1SyPFI2QDN2NECx
MDA-MB-231 M4rHUGZ2dmO2aX;uJGF{e2G7 NVnUZmZZPSEQvF2= MkPqNlQhcA>? MmjsSG1UVw>? M3vLU2lv\HWlZYOgS|MwVSCjcoLld5Q> NVHsWVJ4OjV6M{S0NFE>
MCF7 MmHxSpVv[3Srb36gRZN{[Xl? NFrufZY2KM7:TR?= MViyOEBp NV;WU41LTE2VTx?= MVXE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNU9ETEN{ MorGNlU5OzR2MEG=
MCF7 NEezbHNHfW6ldHnvckBCe3OjeR?= NGS3eII2KM7:TR?= NXLwdlNKOjRiaB?= NEPKVYJFVVOR MkLnSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET|I> MmXUNlU5OzR2MEG=
MCF7 NHTiVJZHfW6ldHnvckBCe3OjeR?= M{L2fFUh|ryP MkOxNlQhcA>? NXHRZ3RUTE2VTx?= NXH6e5VvTGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJIN6[2yrbjDCNS=> MkK3NlU5OzR2MEG=
MCF7 NXHKZYlqTnWwY4Tpc44hSXO|YYm= NIHNSGQ2KM7:TR?= M120ZlI1KGh? MXvEUXNQ NXPrR3UzUW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJJAzOSCZYX[xM2NqeDF? NYDUOHlNOjV6M{S0NFE>
MCF7 MlrFSpVv[3Srb36gRZN{[Xl? NE[3VVA2KM7:TR?= M13zUFI1KGh? MWXEUXNQ M{HxO2lv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?= NE\CW5czPTh|NESwNS=>
MDA-MB-231 MnPDSpVv[3Srb36gRZN{[Xl? Mo\yOUDPxE1? NEnEVZMzPCCq MoDQSG1UVw>? M{HIR2Rm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsyN0OGQ{K= NHfB[G8zPTh|NESwNS=>
MDA-MB-231 MUjGeY5kfGmxbjDBd5NigQ>? MYqxJO69VQ>? NHPye2ozPCCq MXHEUXNQ M4rmPWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz NIH2TIczPTh|NESwNS=>
MDA-MB-231 M4PFPGZ2dmO2aX;uJGF{e2G7 NWPBU4FvPSEQvF2= MkfPNlQhcA>? MUTEUXNQ NE\VN25F\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gZ5lkdGmwIFKx MVKyOVg{PDRyMR?=
MDA-MB-231 NWjsTYo6TnWwY4Tpc44hSXO|YYm= NWO0fJo5PSEQvF2= MmrENlQhcA>? NH\FcHRFVVOR MnjvTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> NVXKV|J{OjV6M{S0NFE>
MDA-MB-231 NY[2VnM{TnWwY4Tpc44hSXO|YYm= NFrKO402KM7:TR?= M3nQUVI1KGh? MYjEUXNQ M3ridWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?= MmmxNlU5OzR2MEG=
MDA-MB-231 M2DsUGZ2dmO2aX;uJGF{e2G7 NY\sOnF{PSEQvF2= NFT2eGUzPCCq NUD5OYw6TE2VTx?= MYfJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEWz M1voN|I2QDN2NECx
MCF7 NXzOXYNKSXCxcITvd4l{KEG|c3H5 NEi5TmE2KM7:TR?= NEO0OoUzPCCq NXP4XIZ2TE2VTx?= NIjKZXBKdmS3Y3XzJIFxd3C2b4TpZ{Bl\WG2aB?= NFzFW2MzPTh|NESwNS=>
MDA-MB-231 MmPyRZBweHSxc3nzJGF{e2G7 M{fHNVUh|ryP NUTib|N1OjRiaB?= MYXEUXNQ NWXIdpNkUW6mdXPld{BieG:ydH;0bYMh\GWjdHi= NGDWVW8zPTh|NESwNS=>
MCF7 MXHGeY5kfGmxbjDBd5NigQ>? M4TjOFEh|ryP MWW3NkBp MVPEUXNQ Moj2TY5lfWOnczDheZRweGijZ3njJIRm[XSq MXWyOVg{PDRyMR?=
MDA-MB-231 MWLGeY5kfGmxbjDBd5NigQ>? NFzZcIoyKM7:TR?= MVK3NkBp M1PDSWROW09? MW\JcoR2[2W|IHH1eI9xcGGpaXOg[IVifGh? M1\SWVI2QDN2NECx
U-2 OS M{PSSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TkeVUxKM7:TR?= M4\YRlI1KGh? MmjnSG1UVw>? MYLJR|UxRTF4Lk[g{txO MWqyOVc6OjhzMR?=
MG-63 NV;2[ZNTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHT4WnM2OCEQvF2= M17nclI1KGh? NYS0OYVVTE2VTx?= NUPHSHprUUN3ME25MlUh|ryP NVjYO4xEOjV5OUK4NVE>
U-2 OS M3fCNWFxd3C2b4Ppd{BCe3OjeR?= M{GzO|Uh|ryP NYe2S3RQOjRiaB?= Mn34SG1UVw>? MnrOTY5lfWOnczDhdI9xfG:2aXOgZ4VtdCCmZXH0bC=> MlTRNlU4QTJ6MUG=
MG-63 M4[wW2Fxd3C2b4Ppd{BCe3OjeR?= MmnoOUDPxE1? MYGyOEBp MVrEUXNQ NW\3V5ZpUW6mdXPld{BieG:ydH;0bYMh[2WubDDk[YF1cA>? M{O4Z|I2Pzl{OEGx
U-2 OS M33jUWZ2dmO2aX;uJGF{e2G7 M2DuSlUh|ryP NHvGVlEzPCCq M{DVT2ROW09? NHyxc3VRem:vb4Tld{BifXSxcHjh[4lkKGOnbHyg[IVifGh? M4\mSFI2Pzl{OEGx
MG-63 NWXRdXlNTnWwY4Tpc44hSXO|YYm= MYC1JO69VQ>? MmDjNlQhcA>? M2TSfmROW09? M1XSVHBzd22xdHXzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? NVzDWYFrOjV5OUK4NVE>
PANC-1 MnG2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHFU4hHPTBizszN MkXONlQhcA>? MUnEUXNQ NE[zN29KSzVyPUeuNUDPxE1? MlLYNlU3OzJ{MkW=
BxPC-3 M2jOVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmHSOVAh|ryP NF;CdG8zPCCq MmLTSG1UVw>? M1vSeGlEPTB;Nj64JO69VQ>? M4jUR|I2PjN{MkK1
PANC-1 M4G5b2Z2dmO2aX;uJGF{e2G7 M{flPVUh|ryP M2raPFI1KGh? NIDN[nJFVVOR M{LXW2lv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgbY4hTzJxTTDwbIF{\Q>? M2juW|I2PjN{MkK1
BxPC-3 MkjoSpVv[3Srb36gRZN{[Xl? MkDQOUDPxE1? MVGyOEBp MkXxSG1UVw>? M4DRVmlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgbY4hTzJxTTDwbIF{\Q>? M3nwUVI2PjN{MkK1
PANC-1 MmfQSpVv[3Srb36gRZN{[Xl? Mk\yOUDPxE1? MoPvNlQhcA>? MYLEUXNQ M{jY[Glv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp NGPkXIMzPTZ|MkKyOS=>
BxPC-3 NEezPY9HfW6ldHnvckBCe3OjeR?= NVHYTFFNPSEQvF2= MX[yOEBp Mn7DSG1UVw>? MWLJcoR2[2W|IHH1eI9xcGGpaXOgZ4VtdCCmZXH0bC=> NEX2RlIzPTZ|MkKyOS=>
SKOV3 NF\DWnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUSxNFAh|ryP MX6yOEBp M2LXcGROW09? MXPJR|UxRTJyLkS4JO69VQ>? NXLx[|VmOjV4MkS3OVA>
OVCAR4 M37H[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1KxS|ExOCEQvF2= NVHhd|dTOjRiaB?= NGrjPIJFVVOR MnPHTWM2OD1{Mj6xN{DPxE1? MXGyOVYzPDd3MB?=
SKOV3 Mn3USpVv[3Srb36gRZN{[Xl? NFnubWM2KM7:TR?= M1mwb|czKGh? MlfJSG1UVw>? MU\JcoR2[2W|IFeyM20h[XK{ZYP0 MmLqNlU3OjR5NUC=
OVCAR4 NELqS2ZHfW6ldHnvckBCe3OjeR?= Mn;4OUDPxE1? MWK3NkBp M4j0[2ROW09? MlzpTY5lfWOnczDHNk9OKGG{cnXzeC=> M1jDUlI2PjJ2N{Ww
SKOV3 Mm\LRZBweHSxc3nzJGF{e2G7 NYK2bHJNPSEQvF2= M3TCOVI1KGh? M{[w[mROW09? MVXJcoR2[2W|IHHwc5B1d3Orcx?= MYKyOVYzPDd3MB?=
OVCAR4 MYPBdI9xfG:|aYOgRZN{[Xl? M{fxT|Uh|ryP NGD2WFIzPCCq NIC5NmlFVVOR NUezWpVKUW6mdXPld{BieG:ydH;zbZM> NYfQfXczOjV4MkS3OVA>
AGS NEPY[JpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILxeFYzPSEQvF2= NUP6NphZOjRiaB?= MkPhSG1UVw>? NY[4endEUUN3ME2xPU4xQSEQvF2= MXqyOVYxQTl{Mx?=
NCI-N78 MorFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmflNlUh|ryP MoTtNlQhcA>? NFvOZYNFVVOR NXfOeppqUUN3ME2yOk4{OyEQvF2= MnHhNlU3ODl7MkO=
AGS NWDqR|RUSXCxcITvd4l{KEG|c3H5 MnnmOUDPxE1? MmLnNlQhcA>? NIPBNYRFVVOR M4TSTGlv\HWlZYOgZZBweHSxc3nz NGTGUY0zPTZyOUmyNy=>
NCI-N78 M1;Fb2Fxd3C2b4Ppd{BCe3OjeR?= NYDsdXcyPSEQvF2= NFTBPJUzPCCq NFLlblBFVVOR MlTxTY5lfWOnczDhdI9xfG:|aYO= NHruNXozPTZyOUmyNy=>
AGS MYjGeY5kfGmxbjDBd5NigQ>? NEXJW5U2KM7:TR?= NIfDS|QzPCCq NX\Hc2hoTE2VTx?= MVrJcoR2[2W|IITo[UBifXSxcHjh[5k> M4jmdFI2PjB7OUKz
NCI-N78 MUjGeY5kfGmxbjDBd5NigQ>? Mn;zOUDPxE1? MUCyOEBp NXjGTYlyTE2VTx?= M1zZS2lv\HWlZYOgeIhmKGG3dH;wbIFogQ>? Mm\WNlU3ODl7MkO=
HSC-3 NIjWOHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnHzNUDPxE1? MoHIOFghcA>? M3PQWGlEPTB;MD61OEDPxE1? MXOyOVM3PjF2Mx?=
GB30 MmPGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDXeJJ[OSEQvF2= NYPMSHV1PyCm Mn3ySG1UVw>? M2jlNWlEPTB;MD6wNVEh|ryP NWO1eGJGOjVzME[0Nlg>
GB9 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlzwNUDPxE1? MUi3JIQ> MUDEUXNQ NInGUZdKSzVyPUCuNFI1KM7:TR?= MmXNNlUyODZ2Mki=
GB169 NXvrVWdST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3jWelEh|ryP MmLDO{Bl NVjDWm9QTE2VTx?= M1jRTmlEPTB;MD6wN|Ih|ryP M3jDUFI2OTB4NEK4
T24 MkDFSpVv[3Srb36gRZN{[Xl? NGjDfY0yKM7:TR?= MnzOOFghcA>? NF7jV2JFVVOR NVm0ZVFtUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> Moi5NlM1ODN4M{O=
RT4 NXvPPYhtTnWwY4Tpc44hSXO|YYm= NXjSVFQ{OSEQvF2= M3PsXVQ5KGh? MYTEUXNQ NH;BXoRKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0 M2TFO|I{PDB|NkOz
UM-UC-3 NHyzW2dHfW6ldHnvckBCe3OjeR?= M3\nS|Eh|ryP MVe0PEBp NXHUXYJOTE2VTx?= NXviW|BSUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> NXrEdVVSOjN2MEO2N|M>
T24 M{W4TWFxd3C2b4Ppd{BCe3OjeR?= MVKzMlE3KM7:TR?= MlPTPVYhcA>? MoWwSG1UVw>? M{\PV2lEPTB;MD6wN|A3KM7:TR?= MU[yN|QxOzZ|Mx?=
RT4 MoTLRZBweHSxc3nzJGF{e2G7 MYSzMlE3KM7:TR?= NFHzdJk6PiCq Ml7FSG1UVw>? NFztcGJKSzVyPUCuNVE6QCEQvF2= NF3FRZozOzRyM{[zNy=>
UM-UC-3 NXzI[JdsSXCxcITvd4l{KEG|c3H5 MoniN{4yPiEQvF2= Ml\XPVYhcA>? NGTtSoxFVVOR Moi0TWM2OD1yLkC0OFkh|ryP NWf6XHVxOjN2MEO2N|M>
OVCAR-5 NWrReo1DTnWwY4Tpc44hSXO|YYm= MoPwOVAhdk1? MVPJcohq[mm2czDj[YxtKG2rZ4LheIlwdg>? MUmyN|M{PDN{Nx?=
SKOV3ip2 MUPGeY5kfGmxbjDBd5NigQ>? Mm\wOVAhdk1? NYC4S3pWUW6qaXLpeJMh[2WubDDtbYdz[XSrb36= NWruSpJoOjN|M{SzNlc>
S462 NG\tO4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWTs[VE4OTByIN88US=> NHLvT484OiCq M33tSGROW09? MVfBeJRmdnWjdHXzJINmdGxiZ4Lve5Rp M3vMZVI{OzJ6MUG0
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Kasumi-1 M4Dlc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2GzbFExKM7:TR?= NHLJPIc6PiCq M3;3OmlEPTB;MD6xNFMh|ryP MXmyNFExQDN|OB?=
Karpas-299 NFTocG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVqxNEDPxE1? NYfvUXIzQTZiaB?= NYK4fI5GUUN3ME2wMlA{QCEQvF2= MWGyNFExQDN|OB?=
Ramos-RA1 NILRRWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFjvNVEyOCEQvF2= M3q2Zlk3KGh? M3SxT2lEPTB;MD6xNlch|ryP MYiyNFExQDN|OB?=

... Click to View More Cell Line Experimental Data

In vivo試験 MLN8237 significantly reduces the tumor burden with tumor growth inhibition (TGI) of 42% and 80% at 15 mg/kg and 30 mg/kg, respectively, and prolongs the survival of mice compared with the control. [2]
臨床試験 A Phase II study of MLN8237 for treatment of patients with ovarian, fallopian tube, or peritoneal carcinoma has been completed.
特集 First orally available inhibitor of Aurora A.

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

Aurora A radioactive Flashplate enzyme assay Aurora A radioactive Flashplate enzyme assay is conducted to determine the nature and degree of MLN8237-mediated inhibition in vitro. Recombinant Aurora A is expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A is conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) is assayed in 50 mM Hepes (pH 7.5), 10 mM MgCl2, 5 mM DTT, 0.05% Tween 20, 2 μM peptide substrate, 3.3 μCi/mL [γ-33P]ATP at 2 μM, and increasing concentrations of MLN8237 by using Image FlashPlates.

細胞アッセイ: [2]

細胞株 MM1.S, MM.1R, LR5, RPMI 8226, DOX40, OPM1, OPM2, INA6, and U266
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 24, 48, and 72 hours
実験の流れ Cells are exposed to various concentrations of MLN8237 for 24, 48, and 72 hours. Cells viability is measured using MTT assay, and cell proliferation is measured using 3[H]-thymidine incorporation. For cell cycle analysis, cells are permeabilized by 70% ethanol at -20 °C, and incubated with 50 μg/mL PI and 20 units/mL RNase-A. DNA content is analyzed by flow cytometry using BDFACS-Canto II and FlowJo software. For the detection of apoptosis and senescence, cells are stained with fluorescein isothiocyanate-annexin V and PI. Apoptotic cells are determined by flow cytometric analysis using BDFACS-Canto II and FlowJo software.

動物実験: [2]

動物モデル Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells
製剤 Formulated in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate
投薬量 ~30 mg/kg/day
投与方法 Orally

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 Alisertib (MLN8237) SDF
分子量 518.92
化学式

C27H20ClFN4O4

CAS No. 1028486-01-2
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 27 mg/mL (52.03 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 15% Captisol 30 mg/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 Benzoic acid, 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxy-

カスタマーフィードバック (10)


Click to enlarge
Rating
Source Cell Stem Cell, 2012, 11, 179-94. Alisertib (MLN8237) purchased from Selleck
Method qPCR
Cell Lines CCE cells
Concentrations 1 uM
Incubation Time 48 h
Results Treatment with the Aurka-specific chemical inhibitor MLN8237 suppressed pluripotency TF expression and decreased fluorescence in the NG4 Nanog-GFP reporter line.

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Rating
Source EMBO J, 2012, 30, 906-19. Alisertib (MLN8237) purchased from Selleck
Method immunofluorescence
Cell Lines HEK293 cells
Concentrations 0.3 μM
Incubation Time 40 min
Results Incubation of cells with the Aurora-A kinase inhibitor MLN8237 (0.3 μM) induced a change in the localisation of endogenous TACC3 and clathrin from the mitotic spindle to the cytoplasm.

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Rating
Source J Cell Biol, 2010, 191, 1315-32. Alisertib (MLN8237) purchased from Selleck
Method DAPI staining
Cell Lines HeLa cells
Concentrations 10/20 nM
Incubation Time 15 min/24 h
Results Depletion of PPP6C resulted in a twofold increase in the pT288 form of Aurora A at prometaphase and metaphase spindles compared with control cells, and addition of 10 nM MLN8237 reversed this increase (Fig. A). Importantly, this partial Aurora A inhibition with 10 nM MLN8237 also reduced the micronucleation seen in PPP6C-depleted cells from 40 to 5% (Fig. B).

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Rating
Source EMBO reports , 2010, 11, 977-984. Alisertib (MLN8237) purchased from Selleck
Method Immunoprecipitation, MS/MS analysis
Cell Lines HeLa cells
Concentrations 0.5 µM
Incubation Time 1 h
Results This phosphopeptide was absent in interphase cells and strongly reduced in mitotic cells treated with the inhibitor.

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Rating
Source EMBO Mol Med, 2013, 5(1), 149-66. Alisertib (MLN8237) purchased from Selleck
Method Immunofluorescence co-staining
Cell Lines Hs294T xenograft
Concentrations 30 mg/kg
Incubation Time 28 days
Results To extend its findings in vivo, we examined senescence (SA-b-Gal staining), DNA damage (53BP1), NF-kB activity (IkB-a) and the SASP (IL-6) in an Hs294T xenograft tumour after MLN 8237 treatment. Tumour tissues treated with MLN8237 were b-galactosidase-positive (blue), 53BP1 (red) was increased.

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Rating
Source Oncogene, 2014, 33, 3550-60. Alisertib (MLN8237) purchased from Selleck
Method Western blot, time-lapse microscopy, flow cytometry
Cell Lines HeLa cells
Concentrations 6-1000 nM
Incubation Time 2 h,8 h,24 h,48 h
Results Alisertib inhibits AURKA and AURKB in a concentration-dependent manner.

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Rating
Source ACS Chem Biol , 2010, 5, 563-576. Alisertib (MLN8237) purchased from Selleck
Method Duplicate radiometric assays
Cell Lines
Concentrations 0.1-1000 nM
Incubation Time
Results These clinical stage compounds MLN8237 and MLN8254, which exhibit subtly different chemistry, display similar potency towards Aurora A in vitro.

Click to enlarge
Rating
Source ACS Chem Biol , 2010, 5, 563-576. Alisertib (MLN8237) purchased from Selleck
Method Colony assays
Cell Lines WT Aurora A-expressing cells
Concentrations 30 nM
Incubation Time 8 d
Results We find that a T217D/W277E double mutant does not induce cellular resistance to MLN8054 or MLN8237 in cells

Click to enlarge
Rating
Source J Biol Chem, 2012, 287, 27670-81. Alisertib (MLN8237) purchased from Selleck
Method Immunofluorescence Microscopy
Cell Lines HeLa cells
Concentrations 100 nM
Incubation Time 2 h
Results The fluorescence intensity of the pT210 signal in the spindle poles was markedly decreasedin Fry-depleted cells. Exposure to MLN8237, a specific inhibitor of Aurora A, also abrogated the pT210 signal in the spindle poles.

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Rating
Source Mol Cancer, 2011, 10, 131. Alisertib (MLN8237) purchased from Selleck
Method immunofluorescence
Cell Lines U2OS cells
Concentrations 20/50 nM
Incubation Time 4 h
Results MLN8237 treatment lasted 4 hours and yielded the induction of spindle abnormalities. Spindles with multiple poles represented 15-20 % of all PM/Ms in M LN8237-treated cultures, comparable to the occurrence in Aurora-Ai cultures. When MON was added, Eg5 was inhibited, and the generation of spindles with fragmented poles in MLN8237-treated cultures was abolished, with a parallel increase in mono polar figures.

文献中の引用 (45)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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