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 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfHV3EyOC53IN88US=> NVrQ[mZEPzJiaB?= M2n1[mROW09? M1rZT2lEPTB;MD6wOEDPxE1? NXz0UVhtOjZzM{[2PFQ>
LS174T MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{n0ZVAvPSEQvF2= Mn\pO|IhcA>? NF23TotFVVOR MmKyTWM2OD1yLkC1JO69VQ>? M2D4VFI3OTN4Nki0
T84 Mm\WS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1H3flAvPSEQvF2= NWfmeJB3PzJiaB?= MoDmSG1UVw>? MVjJR|UxRTBwMEmg{txO NWPkUHF1OjZzM{[2PFQ>
LS180 NVfxWW9mT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{nsRVAvPSEQvF2= NX6wTmFXPzJiaB?= MYTEUXNQ MVXJR|UxRTFizszN MlLpNlYyOzZ4OES=
SW948 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH[xO5gxNjVizszN NXfId2hrPzJiaB?= MVnEUXNQ MYPJR|UxRTFizszN MVKyOlE{PjZ6NB?=
HCT15 M3LNS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEWzbnQxNjVizszN M{\0d|czKGh? MXzEUXNQ MYTJR|UxRDBwNDFOwG0> M3XW[lI3OTN4Nki0
DLD-1 MoXCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV7XOIFTOC53IN88US=> M{PWRVczKGh? MV7EUXNQ MVnJR|UxRDBwODFOwG0> MmfyNlYyOzZ4OES=
MIP-101 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFjoUnMxNjVizszN NFLTUmw4OiCq MmjGSG1UVw>? NITpWGtKSzVyPUGg{txO NHnYWZgzPjF|Nk[4OC=>
SNU1544 MkH0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\ONE42KM7:TR?= NHm2dHo4OiCq Mme2SG1UVw>? NUe1cnExUUN3ME2xJO69VQ>? NVnNdGpoOjZzM{[2PFQ>
OCI-Ly10 NWKxSZZlS3m2b4TvfIlkKEG|c3H5 NXXUdnRbPzJiaB?= M{\wbGROW09? MVrJR|UxRTBwMEW4JO69VQ>? M3LncVI2QDd6M{Ox
SU-DHL2 M1PoVWN6fG:2b4jpZ{BCe3OjeR?= NVLGNnluPzJiaB?= NFT3VWJFVVOR NVTDfZV7UUN3ME2wMlAyKM7:TR?= MYSyOVg4QDN|MR?=
OCI-LY7 MnnrR5l1d3SxeHnjJGF{e2G7 MX63NkBp MX3EUXNQ NWHQdmtYUUN3ME2wMlA5OSEQvF2= MmrRNlU5Pzh|M{G=
SU-DHL6 M2TCbmN6fG:2b4jpZ{BCe3OjeR?= M2fnWFczKGh? M3nQbmROW09? M3SxXGlEPTB;MD60PFIh|ryP NVH3OndQOjV6N{izN|E>
Jeko-1 NX3BV3NKS3m2b4TvfIlkKEG|c3H5 MWe3NkBp NVv2S3k2TE2VTx?= M{jrbWlEPTB;MD6wNlkh|ryP NU\GT|BJOjV6N{izN|E>
JVM-2 MnnzR5l1d3SxeHnjJGF{e2G7 MYG3NkBp NH;2eGxFVVOR MmjwTWM2OD1yLkCxJO69VQ>? MkHvNlU5Pzh|M{G=
Rec-1 MUHDfZRwfG:6aXOgRZN{[Xl? NYXoO5U6PzJiaB?= MX\EUXNQ NXrVeHpXUUN3ME2wMlA5PyEQvF2= Ml\kNlU5Pzh|M{G=
Z-138 M{PPZ2N6fG:2b4jpZ{BCe3OjeR?= M3\SUVczKGh? NGnKWXZFVVOR NEmxWmRKSzVyPUCuNFE{KM7:TR?= Mk\mNlU5Pzh|M{G=
H9 NXvLVm1XS3m2b4TvfIlkKEG|c3H5 MmDyO|IhcA>? MmGzSG1UVw>? M3jKfmlEPTB;MD62JO69VQ>? MV2yOVg4QDN|MR?=
HH NF7zRZFEgXSxdH;4bYMhSXO|YYm= M4Htd|czKGh? NGTMcllFVVOR MkTUTWM2OD1yLkeg{txO M4HJNVI2QDd6M{Ox
DND41 MV;DfZRwfG:6aXOgRZN{[Xl? NX;nO5VTPzJiaB?= M{nWSWROW09? MX;JR|UxRTBwMTFOwG0> MVeyOVg4QDN|MR?=
CCL119 M3PDVmN6fG:2b4jpZ{BCe3OjeR?= NXOyd|RVPzJiaB?= NEnBZmVFVVOR NU\VcGxYUUN3ME2wMlA3OiEQvF2= M2P6NFI2QDd6M{Ox
J.Cam 1.6 Mm\rR5l1d3SxeHnjJGF{e2G7 M4PKVFczKGh? NV\JbVY4TE2VTx?= NUnyT5dvUUN3ME2wMlExPSEQvF2= MkDINlU5Pzh|M{G=
Sup-T1 NYTnb41wS3m2b4TvfIlkKEG|c3H5 Mnv4O|IhcA>? NEDHU3hFVVOR NYLjS2VmUUN3ME2yMlE1OiEQvF2= NVf6N5pPOjV6N{izN|E>
Tib 152 NVexTm41S3m2b4TvfIlkKEG|c3H5 NILoeXM4OiCq NYi0OGVsTE2VTx?= NGW1cJJKSzVyPUCuPEDPxE1? MYiyOVg4QDN|MR?=
MCF7 NXTQR4tMTnWwY4Tpc44hSXO|YYm= Mni3OUDPxE1? MoTSNlQhcA>? MkHlSG1UVw>? MWjJcoR2[2W|IFeyM20h[XK{ZYP0 NV\OdY5[OjV6M{S0NFE>
MDA-MB-231 MnfYSpVv[3Srb36gRZN{[Xl? NYnjW4dnPSEQvF2= NWDuWYY6OjRiaB?= M1\5OWROW09? NF:zd|hKdmS3Y3XzJGc{N01iYYLy[ZN1 M1XW[FI2QDN2NECx
MCF7 M4jrd2Z2dmO2aX;uJGF{e2G7 NUGxbYJHPSEQvF2= M2nuN|I1KGh? NWnud|FzTE2VTx?= NXLSVoJ4TGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=> MVKyOVg{PDRyMR?=
MCF7 M2DkVGZ2dmO2aX;uJGF{e2G7 NWjTT3NkPSEQvF2= MV6yOEBp Mnf2SG1UVw>? MVnE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNi=> MUKyOVg{PDRyMR?=
MCF7 NYLQU2c6TnWwY4Tpc44hSXO|YYm= MmTkOUDPxE1? NWfhTYpHOjRiaB?= MXPEUXNQ M1XJO2Rm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG= NVnwTo9lOjV6M{S0NFE>
MCF7 NUDIU4xXTnWwY4Tpc44hSXO|YYm= NUW2VFR5PSEQvF2= MWmyOEBp NGL0XFFFVVOR Ml\YTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> NHX2VIUzPTh|NESwNS=>
MCF7 M4\H[WZ2dmO2aX;uJGF{e2G7 MYW1JO69VQ>? M4qyO|I1KGh? MlvQSG1UVw>? M4fOPWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?= NIrS[okzPTh|NESwNS=>
MDA-MB-231 M1XSVWZ2dmO2aX;uJGF{e2G7 MoHtOUDPxE1? NI\LfXUzPCCq M37L[2ROW09? Ml:2SIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET|EwS0SFMh?= MkfsNlU5OzR2MEG=
MDA-MB-231 NGrEc|BHfW6ldHnvckBCe3OjeR?= NHjMW3gyKM7:TR?= M1H0UlI1KGh? MUXEUXNQ M3LUS2lv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz NEK1NWUzPTh|NESwNS=>
MDA-MB-231 MVfGeY5kfGmxbjDBd5NigQ>? M4rJWlUh|ryP M2Hpe|I1KGh? NF:wfnNFVVOR M322ZWRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG= M2TobVI2QDN2NECx
MDA-MB-231 NWfOdo15TnWwY4Tpc44hSXO|YYm= NGXwS242KM7:TR?= M{\jVFI1KGh? M3[4bmROW09? M1;aSWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlEhX2GoMT;DbZAy NXzmOYsxOjV6M{S0NFE>
MDA-MB-231 MkfjSpVv[3Srb36gRZN{[Xl? MVm1JO69VQ>? M3LYZ|I1KGh? NYPQPFd[TE2VTx?= MlPwTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyO{BMcXBz NVPQPJcyOjV6M{S0NFE>
MDA-MB-231 NE\hZXVHfW6ldHnvckBCe3OjeR?= NVrQU5FIPSEQvF2= NXLYfIV{OjRiaB?= MnvZSG1UVw>? NWnUW5czUW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJJA2Ow>? MlS3NlU5OzR2MEG=
MCF7 NV;IS|VGSXCxcITvd4l{KEG|c3H5 MY[1JO69VQ>? M2nHZVI1KGh? MmjBSG1UVw>? MnXrTY5lfWOnczDhdI9xfG:2aXOg[IVifGh? MmPqNlU5OzR2MEG=
MDA-MB-231 MUHBdI9xfG:|aYOgRZN{[Xl? NYnsRnFyPSEQvF2= NEXPO|IzPCCq M373OmROW09? Mn7hTY5lfWOnczDhdI9xfG:2aXOg[IVifGh? MYGyOVg{PDRyMR?=
MCF7 Mn36SpVv[3Srb36gRZN{[Xl? NWXPUGZEOSEQvF2= NF;sdVQ4OiCq NXT6fo9KTE2VTx?= NFz1W5JKdmS3Y3XzJIF2fG:yaHHnbYMh\GWjdHi= NFO4fXYzPTh|NESwNS=>
MDA-MB-231 NYfX[5NwTnWwY4Tpc44hSXO|YYm= NEfJV3oyKM7:TR?= MUG3NkBp NX;zTlJrTE2VTx?= Ml\DTY5lfWOnczDheZRweGijZ3njJIRm[XSq NILNWpgzPTh|NESwNS=>
U-2 OS NXfSRW0{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDobXhSPTBizszN MUOyOEBp MYDEUXNQ M363VmlEPTB;MU[uOkDPxE1? M{P1O|I2Pzl{OEGx
MG-63 MnzKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4mwSVUxKM7:TR?= M3vsOFI1KGh? NX3aN5dqTE2VTx?= NHi4PJlKSzVyPUmuOUDPxE1? NVPDWodqOjV5OUK4NVE>
U-2 OS MorHRZBweHSxc3nzJGF{e2G7 NXLY[mUyPSEQvF2= MYCyOEBp NGK4OGpFVVOR M4Cwdmlv\HWlZYOgZZBweHSxdHnjJINmdGxiZHXheIg> MYWyOVc6OjhzMR?=
MG-63 M1PvSmFxd3C2b4Ppd{BCe3OjeR?= NHW3N4Q2KM7:TR?= NHrDeZYzPCCq MUDEUXNQ MoLzTY5lfWOnczDhdI9xfG:2aXOgZ4VtdCCmZXH0bC=> NV[zZZc{OjV5OUK4NVE>
U-2 OS Mke2SpVv[3Srb36gRZN{[Xl? NE\GUnI2KM7:TR?= NIrJ[oEzPCCq NVjWcmgyTE2VTx?= NXvrUYJZWHKxbX;0[ZMh[XW2b4DoZYdq[yClZXzsJIRm[XSq NHvlfJozPTd7MkixNS=>
MG-63 MonhSpVv[3Srb36gRZN{[Xl? MkfFOUDPxE1? MWCyOEBp NULqeW1GTE2VTx?= NYTLNVRKWHKxbX;0[ZMh[XW2b4DoZYdq[yClZXzsJIRm[XSq MlK2NlU4QTJ6MUG=
PANC-1 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYXMOms1PTBizszN MkfUNlQhcA>? M1rzOmROW09? MUXJR|UxRTdwMTFOwG0> NYTDcW5pOjV4M{KyNlU>
BxPC-3 NEHYToxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEK3Tmk2OCEQvF2= MlvENlQhcA>? MW\EUXNQ Mmr0TWM2OD14Lkig{txO MkPXNlU3OzJ{MkW=
PANC-1 NXHTblkzTnWwY4Tpc44hSXO|YYm= M{jpXFUh|ryP NYr5S4lxOjRiaB?= MnS1SG1UVw>? MV3JcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2IHnuJGczN01icHjhd4U> MnPGNlU3OzJ{MkW=
BxPC-3 MWfGeY5kfGmxbjDBd5NigQ>? MYW1JO69VQ>? MXWyOEBp MXTEUXNQ MY\JcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2IHnuJGczN01icHjhd4U> MmLUNlU3OzJ{MkW=
PANC-1 MlfsSpVv[3Srb36gRZN{[Xl? NY\yPFN5PSEQvF2= M4TmZlI1KGh? MYrEUXNQ M2G4R2lv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp NWn5dWl{OjV4M{KyNlU>
BxPC-3 NWHxNmdoTnWwY4Tpc44hSXO|YYm= MlXGOUDPxE1? NWHHPWFMOjRiaB?= M4LmTGROW09? MlTPTY5lfWOnczDheZRweGijZ3njJINmdGxiZHXheIg> NGLrR5AzPTZ|MkKyOS=>
SKOV3 NHLvTZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4DZWFExOCEQvF2= Ml24NlQhcA>? NUC4PHI3TE2VTx?= M17i[mlEPTB;MkCuOFgh|ryP Ml7WNlU3OjR5NUC=
OVCAR4 NULpUndJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIO1VnUyODBizszN Ml7vNlQhcA>? MoX1SG1UVw>? M3juU2lEPTB;MkKuNVMh|ryP M{nqVlI2PjJ2N{Ww
SKOV3 NUj4SoJpTnWwY4Tpc44hSXO|YYm= M{nPc|Uh|ryP MX:3NkBp MofNSG1UVw>? MXvJcoR2[2W|IFeyM20h[XK{ZYP0 MWiyOVYzPDd3MB?=
OVCAR4 NFfUXVNHfW6ldHnvckBCe3OjeR?= NGTwZVc2KM7:TR?= Ml\5O|IhcA>? NHHTTpdFVVOR MonDTY5lfWOnczDHNk9OKGG{cnXzeC=> NWH5d4JLOjV4MkS3OVA>
SKOV3 MXnBdI9xfG:|aYOgRZN{[Xl? MX:1JO69VQ>? MX:yOEBp MXHEUXNQ NWj2cYZ6UW6mdXPld{BieG:ydH;zbZM> NUG4XmdtOjV4MkS3OVA>
OVCAR4 MmH3RZBweHSxc3nzJGF{e2G7 NIjYVGE2KM7:TR?= M4rJ[|I1KGh? MlHiSG1UVw>? NULUd4lLUW6mdXPld{BieG:ydH;zbZM> NFLMXFgzPTZ{NEe1NC=>
AGS Mo\oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2TP[FI2KM7:TR?= Ml3wNlQhcA>? Ml3wSG1UVw>? NYSzRmwxUUN3ME2xPU4xQSEQvF2= NXm5b4xIOjV4MEm5NlM>
NCI-N78 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGCxWY8zPSEQvF2= M2XQOlI1KGh? NYr3SZpiTE2VTx?= NVTOfZVkUUN3ME2yOk4{OyEQvF2= MUeyOVYxQTl{Mx?=
AGS MXzBdI9xfG:|aYOgRZN{[Xl? M4nkWFUh|ryP Mn6yNlQhcA>? MWLEUXNQ NEK1ZnNKdmS3Y3XzJIFxd3C2b4Ppdy=> NH\3WGMzPTZyOUmyNy=>
NCI-N78 MmHxRZBweHSxc3nzJGF{e2G7 NInwW2Y2KM7:TR?= NE\FXHYzPCCq NVe4SmZvTE2VTx?= NUP2ZWNtUW6mdXPld{BieG:ydH;zbZM> MoS1NlU3ODl7MkO=
AGS NIG4eZNHfW6ldHnvckBCe3OjeR?= NFfZXGE2KM7:TR?= MVOyOEBp MXjEUXNQ NHW3W5ZKdmS3Y3XzJJRp\SCjdYTvdIhi\3l? MX6yOVYxQTl{Mx?=
NCI-N78 NX3yUJRVTnWwY4Tpc44hSXO|YYm= NH[0U2c2KM7:TR?= NWjROVJvOjRiaB?= M1HxeGROW09? MmL6TY5lfWOnczD0bIUh[XW2b4DoZYd6 M{H0blI2PjB7OUKz
HSC-3 NIeyc5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3LJZVEh|ryP M2j0TVQ5KGh? NVfDT5dDUUN3ME2wMlU1KM7:TR?= MmjrNlU{PjZzNEO=
GB30 MnzwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M17rNVEh|ryP MmPEO{Bl MVzEUXNQ NFfjWmdKSzVyPUCuNFEyKM7:TR?= M4DxPVI2OTB4NEK4
GB9 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWSxJO69VQ>? NUDi[pp[PyCm M1LJNWROW09? M3jjXWlEPTB;MD6wNlQh|ryP NETITIgzPTFyNkSyPC=>
GB169 NFLtOYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXzMXY1xOSEQvF2= NFj5e5I4KGR? NGLLVVNFVVOR M2PnV2lEPTB;MD6wN|Ih|ryP NGfxdpUzPTFyNkSyPC=>
T24 NVP5bmR[TnWwY4Tpc44hSXO|YYm= MkmzNUDPxE1? NUj4cXV6PDhiaB?= MYXEUXNQ MkeyTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= NID2e4czOzRyM{[zNy=>
RT4 MlrPSpVv[3Srb36gRZN{[Xl? NH3yOosyKM7:TR?= NH[2XGo1QCCq NH\JfoZFVVOR NUP2cIRZUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> MoXPNlM1ODN4M{O=
UM-UC-3 MkDDSpVv[3Srb36gRZN{[Xl? NYXxPIhVOSEQvF2= NGm5eYQ1QCCq M1LaO2ROW09? Mn72TY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= NXXyWY1EOjN2MEO2N|M>
T24 M{jGXmFxd3C2b4Ppd{BCe3OjeR?= MV:zMlE3KM7:TR?= NGH6Rmk6PiCq MULEUXNQ M{W4[2lEPTB;MD6wN|A3KM7:TR?= NGCwfWozOzRyM{[zNy=>
RT4 NHPaVppCeG:ydH;zbZMhSXO|YYm= M1\2RVMvOTZizszN MYG5OkBp NFPsdlVFVVOR NGDI[oxKSzVyPUCuNVE6QCEQvF2= NUTBTpdqOjN2MEO2N|M>
UM-UC-3 NFKzNIFCeG:ydH;zbZMhSXO|YYm= NHj4eXo{NjF4IN88US=> NH3rRok6PiCq M{HHOmROW09? NWf5UFhiUUN3ME2wMlA1PDlizszN NX;DNIk1OjN2MEO2N|M>
OVCAR-5 NV:5OpF2TnWwY4Tpc44hSXO|YYm= NXO5RZpkPTBibl2= NWXNPYREUW6qaXLpeJMh[2WubDDtbYdz[XSrb36= MmPVNlM{OzR|Mke=
SKOV3ip2 NILpSYJHfW6ldHnvckBCe3OjeR?= MoKyOVAhdk1? NEL1T4VKdmirYnn0d{Bk\WyuIH3p[5JifGmxbh?= NETvT4UzOzN|NEOyOy=>
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MOLT-4 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1\NNVExKM7:TR?= M3zRbFk3KGh? M3i2[GlEPTB;MD6wNlYh|ryP NUDWbItuOjBzMEizN|g>
CCRF-CEM NHjuOnNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NITw[WQyOCEQvF2= MoXoPVYhcA>? NI\6[GxKSzVyPUCuNFk1KM7:TR?= MYSyNFExQDN|OB?=
Kasumi-1 M3PxU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfEOm11OTBizszN Ml[2PVYhcA>? NHTWfW9KSzVyPUCuNVA{KM7:TR?= NGD4R2szODFyOEOzPC=>
Karpas-299 NVTESIhmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPVc5lHOTBizszN NGH2PIc6PiCq NFzFSYtKSzVyPUCuNFM5KM7:TR?= NF\afZgzODFyOEOzPC=>
Ramos-RA1 NWryZ2VMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGS2SoEyOCEQvF2= MWO5OkBp MnftTWM2OD1yLkGyO{DPxE1? NWrPTYROOjBzMEizN|g>

... 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)


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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.

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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

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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 (46)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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