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 NIXJSlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXVNE42KM7:TR?= MlH6O|IhcA>? M4P2TGROW09? MVjJR|UxRTBwMESg{txO NUm5OFRyOjZzM{[2PFQ>
LS174T NYr1NI86T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;KcI4xNjVizszN MYi3NkBp Mlf0SG1UVw>? MVjJR|UxRTBwMEWg{txO M2j5OFI3OTN4Nki0
T84 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\hVVAvPSEQvF2= NUHxWnl6PzJiaB?= NGntT|hFVVOR NGLHcpFKSzVyPUCuNFkh|ryP MnfKNlYyOzZ4OES=
LS180 NVzWPJZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFfPbWQxNjVizszN M17ZSFczKGh? NXLpbFFtTE2VTx?= NH3OUolKSzVyPUGg{txO MmWwNlYyOzZ4OES=
SW948 Ml;4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fzNVAvPSEQvF2= NFTrfmM4OiCq MnHQSG1UVw>? M37NNWlEPTB;MTFOwG0> NFzGZYYzPjF|Nk[4OC=>
HCT15 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4jReVAvPSEQvF2= NGPvR4w4OiCq MkjnSG1UVw>? NFH3PZVKSzVyPECuOEDPxE1? MXuyOlE{PjZ6NB?=
DLD-1 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUfvZWc2OC53IN88US=> MYW3NkBp MX;EUXNQ MnvDTWM2ODxyLkig{txO M2W1N|I3OTN4Nki0
MIP-101 MlPlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF3yVFMxNjVizszN NF:wZVY4OiCq MVjEUXNQ MoL3TWM2OD1zIN88US=> MoXqNlYyOzZ4OES=
SNU1544 NX\tSWtTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWGwMlUh|ryP NIe4SnM4OiCq M1nZVmROW09? NHPWR2ZKSzVyPUGg{txO M2nsb|I3OTN4Nki0
OCI-Ly10 NEjCSG5EgXSxdH;4bYMhSXO|YYm= NHnGNYc4OiCq MX3EUXNQ MXTJR|UxRTBwMEW4JO69VQ>? MUmyOVg4QDN|MR?=
SU-DHL2 NInUXWtEgXSxdH;4bYMhSXO|YYm= MlnCO|IhcA>? MlzuSG1UVw>? MkPETWM2OD1yLkCxJO69VQ>? M1jCNlI2QDd6M{Ox
OCI-LY7 NYrHNYNMS3m2b4TvfIlkKEG|c3H5 NGG4RZU4OiCq M{PrOWROW09? M3fJOGlEPTB;MD6wPFEh|ryP M{\abFI2QDd6M{Ox
SU-DHL6 MlLUR5l1d3SxeHnjJGF{e2G7 MVO3NkBp NIHJelJFVVOR NHi1UWtKSzVyPUCuOFgzKM7:TR?= M3vCb|I2QDd6M{Ox
Jeko-1 MUHDfZRwfG:6aXOgRZN{[Xl? NGXwboI4OiCq MUfEUXNQ MmDETWM2OD1yLkCyPUDPxE1? MUOyOVg4QDN|MR?=
JVM-2 MUTDfZRwfG:6aXOgRZN{[Xl? M4K2cVczKGh? MW\EUXNQ MUHJR|UxRTBwMEGg{txO NX7P[3pNOjV6N{izN|E>
Rec-1 MY\DfZRwfG:6aXOgRZN{[Xl? M1jmblczKGh? MlfGSG1UVw>? MkD4TWM2OD1yLkC4O{DPxE1? NXHEdZRROjV6N{izN|E>
Z-138 MlXLR5l1d3SxeHnjJGF{e2G7 MmXMO|IhcA>? MoTzSG1UVw>? NH32WGVKSzVyPUCuNFE{KM7:TR?= NXnHWIRZOjV6N{izN|E>
H9 M2D0WGN6fG:2b4jpZ{BCe3OjeR?= NHzBWo84OiCq MXjEUXNQ NUXXSZgzUUN3ME2wMlYh|ryP MlX3NlU5Pzh|M{G=
HH M4\ZSGN6fG:2b4jpZ{BCe3OjeR?= MlnpO|IhcA>? MlS2SG1UVw>? M1TTTGlEPTB;MD63JO69VQ>? MYSyOVg4QDN|MR?=
DND41 NXfzcWlRS3m2b4TvfIlkKEG|c3H5 Mn3UO|IhcA>? M1P2PWROW09? NEDPd5NKSzVyPUCuNUDPxE1? NHXUNXEzPTh5OEOzNS=>
CCL119 NIn1[nhEgXSxdH;4bYMhSXO|YYm= M1[3[FczKGh? M1:4V2ROW09? NV[3OIdpUUN3ME2wMlA3OiEQvF2= MWWyOVg4QDN|MR?=
J.Cam 1.6 NX;vWZp2S3m2b4TvfIlkKEG|c3H5 M2TmPFczKGh? NGTyTHVFVVOR Ml7YTWM2OD1yLkGwOUDPxE1? MWSyOVg4QDN|MR?=
Sup-T1 MXXDfZRwfG:6aXOgRZN{[Xl? MnvVO|IhcA>? NH\zUWVFVVOR NIL0TpBKSzVyPUKuNVQzKM7:TR?= MXyyOVg4QDN|MR?=
Tib 152 MW\DfZRwfG:6aXOgRZN{[Xl? NYr1ZmYzPzJiaB?= NVrwWVMzTE2VTx?= M3n6eWlEPTB;MD64JO69VQ>? MXeyOVg4QDN|MR?=
MCF7 MYfGeY5kfGmxbjDBd5NigQ>? MV61JO69VQ>? NG\iclMzPCCq NFztcnlFVVOR M{CzfWlv\HWlZYOgS|IwVSCjcoLld5Q> NFLDSHIzPTh|NESwNS=>
MDA-MB-231 MYfGeY5kfGmxbjDBd5NigQ>? NH\ETlA2KM7:TR?= NGHPSG4zPCCq MVnEUXNQ NH[zTVhKdmS3Y3XzJGc{N01iYYLy[ZN1 NV;JUGw3OjV6M{S0NFE>
MCF7 NF7tXHFHfW6ldHnvckBCe3OjeR?= MoO2OUDPxE1? NXLESIk6OjRiaB?= MoOzSG1UVw>? M3frUmRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsyN0OGQ{K= NFHi[Y8zPTh|NESwNS=>
MCF7 M3Szc2Z2dmO2aX;uJGF{e2G7 M1PpNFUh|ryP M3;0T|I1KGh? MnfUSG1UVw>? MUjE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNi=> NVO5eWN5OjV6M{S0NFE>
MCF7 MWDGeY5kfGmxbjDBd5NigQ>? MoHFOUDPxE1? NYnre3FWOjRiaB?= NWTHfHFoTE2VTx?= MXrE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiY4njcIlvKEJz MnnUNlU5OzR2MEG=
MCF7 NV3Seo5KTnWwY4Tpc44hSXO|YYm= MUG1JO69VQ>? M1[xXFI1KGh? NIH3bFJFVVOR MWHJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEKxJHdi\jFxQ3nwNS=> NXi2OIFWOjV6M{S0NFE>
MCF7 NWjpRW4yTnWwY4Tpc44hSXO|YYm= NVHkeGdxPSEQvF2= MkfHNlQhcA>? M1TydGROW09? NET1VXdKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFI4KEurcEG= NX7wR40zOjV6M{S0NFE>
MDA-MB-231 Ml[xSpVv[3Srb36gRZN{[Xl? M{HFcVUh|ryP NHfkc2IzPCCq NIXtfVBFVVOR MnXaSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET|EwS0SFMh?= M1G5[lI2QDN2NECx
MDA-MB-231 MVjGeY5kfGmxbjDBd5NigQ>? M2fYfFEh|ryP NXnOSWpVOjRiaB?= MlrLSG1UVw>? MorJTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET|I> NFPrW4szPTh|NESwNS=>
MDA-MB-231 NHTzc3NHfW6ldHnvckBCe3OjeR?= NUPiVZRGPSEQvF2= M3ziOFI1KGh? NGrtSZdFVVOR Mmm1SIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIHP5Z4xqdiCEMR?= NEHlOHczPTh|NESwNS=>
MDA-MB-231 NWX3NHByTnWwY4Tpc44hSXO|YYm= MmjHOUDPxE1? NXT3TnJKOjRiaB?= MWHEUXNQ M3:5Vmlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlEhX2GoMT;DbZAy NUfUXXNROjV6M{S0NFE>
MDA-MB-231 MnuxSpVv[3Srb36gRZN{[Xl? NUfBS2J1PSEQvF2= NUXsbJhQOjRiaB?= NUDnU2Z1TE2VTx?= NFTTRmdKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFI4KEurcEG= MYSyOVg{PDRyMR?=
MDA-MB-231 MWLGeY5kfGmxbjDBd5NigQ>? M1LHfVUh|ryP NGrBXW4zPCCq NYXwVYF1TE2VTx?= NFHhRXhKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFU{ NXr3cJN4OjV6M{S0NFE>
MCF7 M2fQ[mFxd3C2b4Ppd{BCe3OjeR?= MlzGOUDPxE1? MnHDNlQhcA>? MWLEUXNQ MXTJcoR2[2W|IHHwc5B1d3SrYzDk[YF1cA>? MmLZNlU5OzR2MEG=
MDA-MB-231 MYHBdI9xfG:|aYOgRZN{[Xl? NES0[oM2KM7:TR?= M3r2W|I1KGh? NIq5N2xFVVOR NY[1WWY5UW6mdXPld{BieG:ydH;0bYMh\GWjdHi= MWOyOVg{PDRyMR?=
MCF7 NHHz[JVHfW6ldHnvckBCe3OjeR?= M4j5cVEh|ryP MXm3NkBp NXu4UGpRTE2VTx?= MmjsTY5lfWOnczDheZRweGijZ3njJIRm[XSq NV\wW3pwOjV6M{S0NFE>
MDA-MB-231 NGTzWphHfW6ldHnvckBCe3OjeR?= M4XtR|Eh|ryP MV:3NkBp MW\EUXNQ NXXpW5VbUW6mdXPld{BifXSxcHjh[4lkKGSnYYTo M{jjVlI2QDN2NECx
U-2 OS MoL2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYfwXGFtPTBizszN M2DCTFI1KGh? MnjRSG1UVw>? M2j6WmlEPTB;MU[uOkDPxE1? MnGzNlU4QTJ6MUG=
MG-63 M3npd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfwVYhOPTBizszN MVOyOEBp Mlz4SG1UVw>? MVvJR|UxRTlwNTFOwG0> M{\1TFI2Pzl{OEGx
U-2 OS MoPrRZBweHSxc3nzJGF{e2G7 MV[1JO69VQ>? MV6yOEBp NVzxZmd1TE2VTx?= NEjiNlNKdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRp MoTzNlU4QTJ6MUG=
MG-63 NXXtNW1XSXCxcITvd4l{KEG|c3H5 M2D6fVUh|ryP MkjINlQhcA>? NG\qOI9FVVOR MUPJcoR2[2W|IHHwc5B1d3SrYzDj[YxtKGSnYYTo NGTxb20zPTd7MkixNS=>
U-2 OS Mn;nSpVv[3Srb36gRZN{[Xl? NUjtO245PSEQvF2= NWXOOJptOjRiaB?= MVfEUXNQ NYDrTWdYWHKxbX;0[ZMh[XW2b4DoZYdq[yClZXzsJIRm[XSq NEP0[JgzPTd7MkixNS=>
MG-63 MnuwSpVv[3Srb36gRZN{[Xl? M2TUblUh|ryP MoizNlQhcA>? NHzwfnBFVVOR NF3Jc5pRem:vb4Tld{BifXSxcHjh[4lkKGOnbHyg[IVifGh? NWfDN3JXOjV5OUK4NVE>
PANC-1 NELBSGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX:1NEDPxE1? MVuyOEBp NFL1ZnVFVVOR M3XKcGlEPTB;Nz6xJO69VQ>? NXPZfnBGOjV4M{KyNlU>
BxPC-3 MkjKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrFOVAh|ryP M{HReFI1KGh? NFrQUJJFVVOR MnfnTWM2OD14Lkig{txO NFHsTZozPTZ|MkKyOS=>
PANC-1 NV\2U5ZTTnWwY4Tpc44hSXO|YYm= M1XPNFUh|ryP M1u2U|I1KGh? M1HMWGROW09? NVrqXYdLUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBqdiCJMj;NJJBp[XOn Mn;oNlU3OzJ{MkW=
BxPC-3 NF;iN|RHfW6ldHnvckBCe3OjeR?= NX7KT4xqPSEQvF2= M{DDXVI1KGh? NYDyNWpKTE2VTx?= NULDVmtEUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBqdiCJMj;NJJBp[XOn NXvlbZhmOjV4M{KyNlU>
PANC-1 MWPGeY5kfGmxbjDBd5NigQ>? NV\afFBqPSEQvF2= NUfXTnV4OjRiaB?= NYTlUmZzTE2VTx?= M3rKTWlv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp NXK4blhbOjV4M{KyNlU>
BxPC-3 MYDGeY5kfGmxbjDBd5NigQ>? NXS1clFzPSEQvF2= M3LWfFI1KGh? NHn2elhFVVOR M3\USGlv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp MXyyOVY{OjJ{NR?=
SKOV3 NU[2d21sT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3O5flExOCEQvF2= MnvDNlQhcA>? MknZSG1UVw>? MUPJR|UxRTJyLkS4JO69VQ>? NXT4NWRsOjV4MkS3OVA>
OVCAR4 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHPYUXoyODBizszN MVuyOEBp MkHJSG1UVw>? M4jSdWlEPTB;MkKuNVMh|ryP NIPZbG0zPTZ{NEe1NC=>
SKOV3 NHHucIJHfW6ldHnvckBCe3OjeR?= NV3vcnhTPSEQvF2= M3v3U|czKGh? NHPySVlFVVOR NXTUbYJEUW6mdXPld{BIOi:PIHHydoV{fA>? Mk\ONlU3OjR5NUC=
OVCAR4 Mny2SpVv[3Srb36gRZN{[Xl? NEDGXpg2KM7:TR?= MmjuO|IhcA>? MWDEUXNQ MV;JcoR2[2W|IFeyM20h[XK{ZYP0 MonvNlU3OjR5NUC=
SKOV3 MVXBdI9xfG:|aYOgRZN{[Xl? MoDNOUDPxE1? NYfIfVNnOjRiaB?= NX3tephsTE2VTx?= MYPJcoR2[2W|IHHwc5B1d3Orcx?= NED1VlgzPTZ{NEe1NC=>
OVCAR4 NXz0UWFnSXCxcITvd4l{KEG|c3H5 NImzO4E2KM7:TR?= M2L2OFI1KGh? NUHpZXFRTE2VTx?= NWTtW|ZiUW6mdXPld{BieG:ydH;zbZM> MlrHNlU3OjR5NUC=
AGS NFXLPFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV7ueGQ3OjVizszN MoDGNlQhcA>? M4rOdGROW09? MoLhTWM2OD1zOT6wPUDPxE1? NF7TNVEzPTZyOUmyNy=>
NCI-N78 NFHMOm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXr4VXMyOjVizszN MnfFNlQhcA>? NXq5O5V4TE2VTx?= NHnCWWFKSzVyPUK2MlM{KM7:TR?= M2L4VFI2PjB7OUKz
AGS MoHaRZBweHSxc3nzJGF{e2G7 MlLOOUDPxE1? MWSyOEBp M2LMTGROW09? Ml7FTY5lfWOnczDhdI9xfG:|aYO= M17uTFI2PjB7OUKz
NCI-N78 MkHqRZBweHSxc3nzJGF{e2G7 M4K3N|Uh|ryP NETj[Y4zPCCq NEe2dW5FVVOR MkL3TY5lfWOnczDhdI9xfG:|aYO= MXeyOVYxQTl{Mx?=
AGS NFP2THJHfW6ldHnvckBCe3OjeR?= M3TxR|Uh|ryP M1XTdVI1KGh? MnPWSG1UVw>? NHmxS5pKdmS3Y3XzJJRp\SCjdYTvdIhi\3l? MVSyOVYxQTl{Mx?=
NCI-N78 M1fCU2Z2dmO2aX;uJGF{e2G7 NInHNmg2KM7:TR?= M{faTlI1KGh? MlvWSG1UVw>? NX7TW|BbUW6mdXPld{B1cGViYYX0c5Bp[We7 NYHqNJQ{OjV4MEm5NlM>
HSC-3 NGPwZXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH7FXZIyKM7:TR?= M2DIbVQ5KGh? M3LVS2lEPTB;MD61OEDPxE1? MUCyOVM3PjF2Mx?=
GB30 M4LCcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVixJO69VQ>? MmS2O{Bl MWXEUXNQ Mlf6TWM2OD1yLkCxNUDPxE1? M3P5TFI2OTB4NEK4
GB9 NFPRNVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFjxT2IyKM7:TR?= MmL4O{Bl M4XyZWROW09? M4DOZmlEPTB;MD6wNlQh|ryP M3rLOlI2OTB4NEK4
GB169 NYP5Xm5rT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NU[wUYVGOSEQvF2= MoLkO{Bl M2G2VWROW09? MmLoTWM2OD1yLkCzNkDPxE1? M1i3TVI2OTB4NEK4
T24 MVXGeY5kfGmxbjDBd5NigQ>? NHv0W5UyKM7:TR?= NVvaUVMxPDhiaB?= NXLQc3I5TE2VTx?= M{fYNGlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= MmexNlM1ODN4M{O=
RT4 M2\0SGZ2dmO2aX;uJGF{e2G7 MofmNUDPxE1? Mlf0OFghcA>? NWjBVJZYTE2VTx?= NY\HUGxGUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> NWTXW2pCOjN2MEO2N|M>
UM-UC-3 M3m0bGZ2dmO2aX;uJGF{e2G7 NETHeYIyKM7:TR?= MnfqOFghcA>? NHmwZ2ZFVVOR Mn7qTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= NWHkSolwOjN2MEO2N|M>
T24 NVfNNpFtSXCxcITvd4l{KEG|c3H5 NETmUG8{NjF4IN88US=> MnWxPVYhcA>? NUfxbWVjTE2VTx?= NFvlZ3NKSzVyPUCuNFMxPiEQvF2= MlrpNlM1ODN4M{O=
RT4 M1XkWGFxd3C2b4Ppd{BCe3OjeR?= NUjyXGdwOy5zNjFOwG0> NX:xWVZrQTZiaB?= MnvSSG1UVw>? NF;mRmJKSzVyPUCuNVE6QCEQvF2= MmHpNlM1ODN4M{O=
UM-UC-3 M3HobWFxd3C2b4Ppd{BCe3OjeR?= MkfON{4yPiEQvF2= MnvYPVYhcA>? MkS2SG1UVw>? NYHOTVZ[UUN3ME2wMlA1PDlizszN Mn7iNlM1ODN4M{O=
OVCAR-5 M3jj[WZ2dmO2aX;uJGF{e2G7 MnHiOVAhdk1? MknWTY5pcWKrdIOgZ4VtdCCvaXfyZZRqd25? MorONlM{OzR|Mke=
SKOV3ip2 MX\GeY5kfGmxbjDBd5NigQ>? M2nxW|UxKG6P M4r3PWlvcGmkaYTzJINmdGxibXnndoF1cW:w NX3JOIFQOjN|M{SzNlc>
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RS4-11 MoLUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTjNVAh|ryP M1LNSVk3KGh? MnXBTWM2OD1yLkCxPEDPxE1? MlSzNlAyODh|M{i=
MOLT-4 NGPtZXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUfCXXRzOTBizszN NFrEfWs6PiCq NFPqR5JKSzVyPUCuNFI3KM7:TR?= MYOyNFExQDN|OB?=
CCRF-CEM MmfRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYmxNEDPxE1? MnXxPVYhcA>? NX7KeXFPUUN3ME2wMlA6PCEQvF2= NHPFPY0zODFyOEOzPC=>
Kasumi-1 NEP3Z5FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvoNVAh|ryP NIX0eoc6PiCq MX7JR|UxRTBwMUCzJO69VQ>? MYGyNFExQDN|OB?=
Karpas-299 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTTNVAh|ryP NFfZbWY6PiCq MXXJR|UxRTBwMEO4JO69VQ>? NUXyWY5FOjBzMEizN|g>
Ramos-RA1 M1jtUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPrRo8yOCEQvF2= M3LZSlk3KGh? NX;2d3h1UUN3ME2wMlEzPyEQvF2= Mn;vNlAyODh|M{i=

... 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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