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 NVvOVodwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUWwMlUh|ryP MVW3NkBp M4LtSGROW09? NFjaU5lKSzVyPUCuNFQh|ryP NWL5[WJGOjZzM{[2PFQ>
LS174T NUjsbGlMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUWwMlUh|ryP NFXtN4Y4OiCq MnT6SG1UVw>? M361bmlEPTB;MD6wOUDPxE1? NGXW[ZUzPjF|Nk[4OC=>
T84 NVTIbXpiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYnCc|NKOC53IN88US=> NIi5Nlc4OiCq NY\kdVNuTE2VTx?= M4ezN2lEPTB;MD6wPUDPxE1? M4XYVVI3OTN4Nki0
LS180 NFrC[YNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV:wMlUh|ryP NGfJd2E4OiCq M3v4N2ROW09? M1vUd2lEPTB;MTFOwG0> Mlr4NlYyOzZ4OES=
SW948 NInWVJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXSwMlUh|ryP MUS3NkBp MoTuSG1UVw>? MW\JR|UxRTFizszN M2XG[|I3OTN4Nki0
HCT15 Ml3kS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUH6U3VWOC53IN88US=> MVG3NkBp Ml\xSG1UVw>? MVvJR|UxRDBwNDFOwG0> MViyOlE{PjZ6NB?=
DLD-1 NWTwOVVXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1PsZVAvPSEQvF2= M1faOlczKGh? M4\6ZmROW09? MkjVTWM2ODxyLkig{txO NIrqRZQzPjF|Nk[4OC=>
MIP-101 NGrXbohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX;3WG11OC53IN88US=> MoT5O|IhcA>? MWTEUXNQ Mor2TWM2OD1zIN88US=> MUKyOlE{PjZ6NB?=
SNU1544 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2HxflAvPSEQvF2= NWnHUJcyPzJiaB?= MX3EUXNQ NWPNdnZCUUN3ME2xJO69VQ>? MmLsNlYyOzZ4OES=
OCI-Ly10 NXfKPVA2S3m2b4TvfIlkKEG|c3H5 NWP2[WwxPzJiaB?= NFPzPYRFVVOR NVPI[m9kUUN3ME2wMlA2QCEQvF2= MXGyOVg4QDN|MR?=
SU-DHL2 NVzpTIxGS3m2b4TvfIlkKEG|c3H5 Mmr0O|IhcA>? NHT1SG5FVVOR Mo\kTWM2OD1yLkCxJO69VQ>? NHTFN2szPTh5OEOzNS=>
OCI-LY7 NF3QZWxEgXSxdH;4bYMhSXO|YYm= NFTibpI4OiCq MW\EUXNQ M3n3TGlEPTB;MD6wPFEh|ryP MXmyOVg4QDN|MR?=
SU-DHL6 NG[3TYhEgXSxdH;4bYMhSXO|YYm= MVS3NkBp M3jzTWROW09? MVHJR|UxRTBwNEiyJO69VQ>? MoewNlU5Pzh|M{G=
Jeko-1 Ml7pR5l1d3SxeHnjJGF{e2G7 NWnnS5Q2PzJiaB?= NE[wcZlFVVOR NGHMWWZKSzVyPUCuNFI6KM7:TR?= MknJNlU5Pzh|M{G=
JVM-2 MnfjR5l1d3SxeHnjJGF{e2G7 NVzN[WRxPzJiaB?= MlXySG1UVw>? Ml;xTWM2OD1yLkCxJO69VQ>? MUOyOVg4QDN|MR?=
Rec-1 MmTVR5l1d3SxeHnjJGF{e2G7 NGXxXYY4OiCq NETwcotFVVOR NFzJbZlKSzVyPUCuNFg4KM7:TR?= MVSyOVg4QDN|MR?=
Z-138 NVXmSVRDS3m2b4TvfIlkKEG|c3H5 MXK3NkBp NYTFTFBITE2VTx?= MknMTWM2OD1yLkCxN{DPxE1? MYWyOVg4QDN|MR?=
H9 MXnDfZRwfG:6aXOgRZN{[Xl? NVThW4hSPzJiaB?= M3vMV2ROW09? M{H3[WlEPTB;MD62JO69VQ>? MnXQNlU5Pzh|M{G=
HH M1jkVmN6fG:2b4jpZ{BCe3OjeR?= M3jENVczKGh? MVrEUXNQ MUPJR|UxRTBwNzFOwG0> MVGyOVg4QDN|MR?=
DND41 MlHIR5l1d3SxeHnjJGF{e2G7 MUO3NkBp NVLES3l3TE2VTx?= M{nkdWlEPTB;MD6xJO69VQ>? NXTkW2IyOjV6N{izN|E>
CCL119 M4fXd2N6fG:2b4jpZ{BCe3OjeR?= MlO2O|IhcA>? MWrEUXNQ NXrZSot3UUN3ME2wMlA3OiEQvF2= MYqyOVg4QDN|MR?=
J.Cam 1.6 MWjDfZRwfG:6aXOgRZN{[Xl? M1XicVczKGh? NUXpNGRFTE2VTx?= M1jwNWlEPTB;MD6xNFUh|ryP NXPGXnFVOjV6N{izN|E>
Sup-T1 NWHwcGFFS3m2b4TvfIlkKEG|c3H5 MX23NkBp MX;EUXNQ NGnaeIZKSzVyPUKuNVQzKM7:TR?= M3XXeFI2QDd6M{Ox
Tib 152 M1zheWN6fG:2b4jpZ{BCe3OjeR?= M3;LU|czKGh? M4L6VGROW09? MnPqTWM2OD1yLkig{txO NF35bHEzPTh5OEOzNS=>
MCF7 MVHGeY5kfGmxbjDBd5NigQ>? NE\q[FE2KM7:TR?= MkjVNlQhcA>? MlX5SG1UVw>? NUDYOYFPUW6mdXPld{BIOi:PIHHydoV{fA>? MXqyOVg{PDRyMR?=
MDA-MB-231 MYTGeY5kfGmxbjDBd5NigQ>? MnLaOUDPxE1? NGnZW4EzPCCq M2PjOGROW09? NXrIPI5sUW6mdXPld{BIOy:PIHHydoV{fA>? NGXOO5QzPTh|NESwNS=>
MCF7 MVTGeY5kfGmxbjDBd5NigQ>? NH;Gc2c2KM7:TR?= MkLpNlQhcA>? MVPEUXNQ MYPE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNU9ETEN{ MUOyOVg{PDRyMR?=
MCF7 Mmr3SpVv[3Srb36gRZN{[Xl? MYG1JO69VQ>? NV;xO|M6OjRiaB?= M3Lr[WROW09? NIi4[YlF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOg>? NXPk[2ZIOjV6M{S0NFE>
MCF7 M1\xTmZ2dmO2aX;uJGF{e2G7 NG\pdlk2KM7:TR?= NEjCNZozPCCq MVrEUXNQ Mn3TSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIHP5Z4xqdiCEMR?= MnvaNlU5OzR2MEG=
MCF7 MoXwSpVv[3Srb36gRZN{[Xl? NFHDc5c2KM7:TR?= M{\zUVI1KGh? NX;jfW9WTE2VTx?= M2ro[Glv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlEhX2GoMT;DbZAy NIXOVZUzPTh|NESwNS=>
MCF7 MXHGeY5kfGmxbjDBd5NigQ>? NUnvb4tpPSEQvF2= MViyOEBp MWPEUXNQ M1X2[Glv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?= NV\NbY9qOjV6M{S0NFE>
MDA-MB-231 NYTtWGp7TnWwY4Tpc44hSXO|YYm= MWq1JO69VQ>? M{\iVlI1KGh? MWDEUXNQ NUKxcmZTTGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=> NHfXOokzPTh|NESwNS=>
MDA-MB-231 MmfqSpVv[3Srb36gRZN{[Xl? MYmxJO69VQ>? NUm5WFJDOjRiaB?= NVjEb|JTTE2VTx?= NXS5RXF2UW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzJ? NUTKS4NsOjV6M{S0NFE>
MDA-MB-231 NInMSZlHfW6ldHnvckBCe3OjeR?= NWrGV|hEPSEQvF2= NInHeZAzPCCq NXjZPXYzTE2VTx?= NYfZNnZYTGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJIN6[2yrbjDCNS=> NIHCNJIzPTh|NESwNS=>
MDA-MB-231 M1n1dWZ2dmO2aX;uJGF{e2G7 NHTXTmM2KM7:TR?= NUXw[IgyOjRiaB?= MlHRSG1UVw>? NInBUYhKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFIyKFejZkGvR4lxOQ>? NWPlSXBsOjV6M{S0NFE>
MDA-MB-231 MX7GeY5kfGmxbjDBd5NigQ>? NG\MVoE2KM7:TR?= NXrpfJhDOjRiaB?= MWHEUXNQ M1TqfWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?= M2DsUVI2QDN2NECx
MDA-MB-231 Ml\MSpVv[3Srb36gRZN{[Xl? NF3oXFQ2KM7:TR?= MlX3NlQhcA>? MXPEUXNQ Mn3FTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIIC1Ny=> NFTwZowzPTh|NESwNS=>
MCF7 NVG2d|llSXCxcITvd4l{KEG|c3H5 M1u2WFUh|ryP MnnINlQhcA>? MXPEUXNQ NF3UZ49KdmS3Y3XzJIFxd3C2b4TpZ{Bl\WG2aB?= MkHWNlU5OzR2MEG=
MDA-MB-231 NGTxW21CeG:ydH;zbZMhSXO|YYm= NVvLc2MzPSEQvF2= NXHWZWxXOjRiaB?= M3zSZWROW09? M1G3T2lv\HWlZYOgZZBweHSxdHnjJIRm[XSq M2\3SVI2QDN2NECx
MCF7 NVO1bFZxTnWwY4Tpc44hSXO|YYm= NUn1OGlQOSEQvF2= MoHFO|IhcA>? MmfnSG1UVw>? M4KyWmlv\HWlZYOgZZV1d3CqYXfpZ{Bl\WG2aB?= M2LFXlI2QDN2NECx
MDA-MB-231 NH3h[GdHfW6ldHnvckBCe3OjeR?= NF7pNIIyKM7:TR?= MYe3NkBp MWPEUXNQ Mn\zTY5lfWOnczDheZRweGijZ3njJIRm[XSq MnPoNlU5OzR2MEG=
U-2 OS MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3TTXFUxKM7:TR?= MXKyOEBp NYPudopiTE2VTx?= M3;lfGlEPTB;MU[uOkDPxE1? M2jHe|I2Pzl{OEGx
MG-63 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnnYOVAh|ryP NGHWXmgzPCCq NUnUTlg1TE2VTx?= M4HjdGlEPTB;OT61JO69VQ>? Mon6NlU4QTJ6MUG=
U-2 OS NEXmNFZCeG:ydH;zbZMhSXO|YYm= NGe3NY02KM7:TR?= NV7YeJZFOjRiaB?= MUHEUXNQ NXntcnR[UW6mdXPld{BieG:ydH;0bYMh[2WubDDk[YF1cA>? NIn1c3MzPTd7MkixNS=>
MG-63 NIX0[4pCeG:ydH;zbZMhSXO|YYm= NFTXOVM2KM7:TR?= M3\BflI1KGh? MmD0SG1UVw>? MUfJcoR2[2W|IHHwc5B1d3SrYzDj[YxtKGSnYYTo M2PBXlI2Pzl{OEGx
U-2 OS Ml;aSpVv[3Srb36gRZN{[Xl? NYnBXodiPSEQvF2= NUnudFlOOjRiaB?= NETTfZlFVVOR M{PCNXBzd22xdHXzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? MXiyOVc6OjhzMR?=
MG-63 MVnGeY5kfGmxbjDBd5NigQ>? NHX6NI02KM7:TR?= MV[yOEBp MV;EUXNQ MVPQdo9ud3SnczDheZRweGijZ3njJINmdGxiZHXheIg> NIHScIYzPTd7MkixNS=>
PANC-1 Ml;DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLqOVAh|ryP MoC3NlQhcA>? NIL2OXZFVVOR NGjNWplKSzVyPUeuNUDPxE1? M1jsblI2PjN{MkK1
BxPC-3 NVHmVHNjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4jIN|UxKM7:TR?= NFv3dHQzPCCq MkfOSG1UVw>? MoTUTWM2OD14Lkig{txO NH;FWmUzPTZ|MkKyOS=>
PANC-1 NIPsW2tHfW6ldHnvckBCe3OjeR?= NEGybJo2KM7:TR?= NV;mN3FLOjRiaB?= MWHEUXNQ NHvyUYZKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V? MU[yOVY{OjJ{NR?=
BxPC-3 MWTGeY5kfGmxbjDBd5NigQ>? NWGzc4QyPSEQvF2= NXLiO5VGOjRiaB?= NGTSfXNFVVOR NGfyW3VKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V? M1nnXlI2PjN{MkK1
PANC-1 NG\IO4tHfW6ldHnvckBCe3OjeR?= NUPEemw3PSEQvF2= MYmyOEBp MkTrSG1UVw>? MYLJcoR2[2W|IHH1eI9xcGGpaXOgZ4VtdCCmZXH0bC=> NV7ZS|E{OjV4M{KyNlU>
BxPC-3 NITYUY1HfW6ldHnvckBCe3OjeR?= M4PPPVUh|ryP NXzBWlVYOjRiaB?= MXHEUXNQ M4rkO2lv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp MlvMNlU3OzJ{MkW=
SKOV3 M{\sS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPKXXUyODBizszN MYSyOEBp M2KyUWROW09? NWm0cW1OUUN3ME2yNE41QCEQvF2= NYO3[2xTOjV4MkS3OVA>
OVCAR4 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXmz[o1ROTByIN88US=> MXyyOEBp MU\EUXNQ NWHwfXdQUUN3ME2yNk4yOyEQvF2= NXXFdol2OjV4MkS3OVA>
SKOV3 MmfDSpVv[3Srb36gRZN{[Xl? NHvVWoI2KM7:TR?= NGTtVZA4OiCq NX;vSXd5TE2VTx?= Ml7rTY5lfWOnczDHNk9OKGG{cnXzeC=> NXrYT3lsOjV4MkS3OVA>
OVCAR4 NYH3cWRDTnWwY4Tpc44hSXO|YYm= MmjKOUDPxE1? MnrVO|IhcA>? M1vyR2ROW09? MUHJcoR2[2W|IFeyM20h[XK{ZYP0 MViyOVYzPDd3MB?=
SKOV3 M{e0NGFxd3C2b4Ppd{BCe3OjeR?= M2njOVUh|ryP M2jVb|I1KGh? MUfEUXNQ NX[3fHQ2UW6mdXPld{BieG:ydH;zbZM> M2P1W|I2PjJ2N{Ww
OVCAR4 NHHvNGlCeG:ydH;zbZMhSXO|YYm= MYW1JO69VQ>? MXGyOEBp NUD2PY9lTE2VTx?= NEK1OpNKdmS3Y3XzJIFxd3C2b4Ppdy=> NHjPdWYzPTZ{NEe1NC=>
AGS MnzCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfJPYYzPSEQvF2= MmfwNlQhcA>? M331[2ROW09? NX;Fb|JOUUN3ME2xPU4xQSEQvF2= M2rTdVI2PjB7OUKz
NCI-N78 NVK2eYNZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoL3NlUh|ryP M3nmXlI1KGh? MnuySG1UVw>? MkfTTWM2OD1{Nj6zN{DPxE1? NFnXSG8zPTZyOUmyNy=>
AGS NHTOPW5CeG:ydH;zbZMhSXO|YYm= M1PpO|Uh|ryP NUOyT2RNOjRiaB?= M3zifWROW09? MoW3TY5lfWOnczDhdI9xfG:|aYO= NVKzU4s5OjV4MEm5NlM>
NCI-N78 MmjaRZBweHSxc3nzJGF{e2G7 NU\RNFNEPSEQvF2= MW[yOEBp M4qx[GROW09? MUnJcoR2[2W|IHHwc5B1d3Orcx?= M{fWWlI2PjB7OUKz
AGS NVrDbZBUTnWwY4Tpc44hSXO|YYm= NWTNT3FjPSEQvF2= M1L1VFI1KGh? M4[yZWROW09? MXLJcoR2[2W|IITo[UBifXSxcHjh[5k> MUGyOVYxQTl{Mx?=
NCI-N78 NEDzdlNHfW6ldHnvckBCe3OjeR?= NH:xdms2KM7:TR?= M1;3[VI1KGh? M4DWSWROW09? MVfJcoR2[2W|IITo[UBifXSxcHjh[5k> M1rFd|I2PjB7OUKz
HSC-3 M33NNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWGxJO69VQ>? MX20PEBp NXLRVJBjUUN3ME2wMlU1KM7:TR?= MmXkNlU{PjZzNEO=
GB30 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoCxNUDPxE1? NWX1PG9DPyCm M3vPRmROW09? MlTrTWM2OD1yLkCxNUDPxE1? MoDGNlUyODZ2Mki=
GB9 NE\Tc2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUixJO69VQ>? NXToPWc3PyCm M2C4cmROW09? MX;JR|UxRTBwMEK0JO69VQ>? MkPmNlUyODZ2Mki=
GB169 M3vQcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nUe|Eh|ryP MV:3JIQ> NH7xRnFFVVOR M1TpRWlEPTB;MD6wN|Ih|ryP MWqyOVExPjR{OB?=
T24 M3nURmZ2dmO2aX;uJGF{e2G7 NUf6eHVDOSEQvF2= NWTTZoJwPDhiaB?= M1Xk[mROW09? NHLQdXVKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0 MmflNlM1ODN4M{O=
RT4 MXrGeY5kfGmxbjDBd5NigQ>? NVqzV3hiOSEQvF2= NETvXWU1QCCq MlzXSG1UVw>? NW\oSW14UW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> MUSyN|QxOzZ|Mx?=
UM-UC-3 MkX4SpVv[3Srb36gRZN{[Xl? MXuxJO69VQ>? NYjlTlluPDhiaB?= MoTISG1UVw>? MVzJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2 NWnINVBqOjN2MEO2N|M>
T24 NGn0WW5CeG:ydH;zbZMhSXO|YYm= MUSzMlE3KM7:TR?= NWD4SJN3QTZiaB?= M{OyZWROW09? MVLJR|UxRTBwMEOwOkDPxE1? NI[zZ5kzOzRyM{[zNy=>
RT4 NHH3OpVCeG:ydH;zbZMhSXO|YYm= NFHMdWc{NjF4IN88US=> MorvPVYhcA>? NYjMOodbTE2VTx?= NYf0SIhuUUN3ME2wMlEyQThizszN MV6yN|QxOzZ|Mx?=
UM-UC-3 NXT3W2pJSXCxcITvd4l{KEG|c3H5 M3;QRlMvOTZizszN MmDaPVYhcA>? M1TFfmROW09? NGf4fW9KSzVyPUCuNFQ1QSEQvF2= NGXFWJgzOzRyM{[zNy=>
OVCAR-5 NH\SNWxHfW6ldHnvckBCe3OjeR?= Mly1OVAhdk1? NFPndItKdmirYnn0d{Bk\WyuIH3p[5JifGmxbh?= MYeyN|M{PDN{Nx?=
SKOV3ip2 MmH2SpVv[3Srb36gRZN{[Xl? M17vOVUxKG6P NF3Kc4pKdmirYnn0d{Bk\WyuIH3p[5JifGmxbh?= MUOyN|M{PDN{Nx?=
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MOLT-4 MmjCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWC4eY5wOTBizszN M37OOFk3KGh? MXjJR|UxRTBwMEK2JO69VQ>? NIG1SpUzODFyOEOzPC=>
CCRF-CEM NGPnOmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYGxNEDPxE1? MVy5OkBp NXH1WlNkUUN3ME2wMlA6PCEQvF2= M1LiclIxOTB6M{O4
Kasumi-1 NUD0SIhmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfrS28yOCEQvF2= M4qzT|k3KGh? MoPxTWM2OD1yLkGwN{DPxE1? MnfNNlAyODh|M{i=
Karpas-299 M2HLe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3\wW|ExKM7:TR?= NFHZOYo6PiCq MUHJR|UxRTBwMEO4JO69VQ>? MUKyNFExQDN|OB?=
Ramos-RA1 NVnoXGU{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnTxNVAh|ryP NGjuS5I6PiCq MnHNTWM2OD1yLkGyO{DPxE1? M2\uU|IxOTB6M{O4

... 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 (45)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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