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 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF\2NZAxNjVizszN MWS3NkBp Ml7vSG1UVw>? MlfJTWM2OD1yLkC0JO69VQ>? Mlv4NlYyOzZ4OES=
LS174T M1;LSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnO5NE42KM7:TR?= NHT0Z4g4OiCq NXfTTW9{TE2VTx?= NFWyTpFKSzVyPUCuNFUh|ryP NF3nVWszPjF|Nk[4OC=>
T84 NGPMR41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzmNE42KM7:TR?= NVfyRWxpPzJiaB?= M1vibmROW09? NFv6Z|FKSzVyPUCuNFkh|ryP NF3rWngzPjF|Nk[4OC=>
LS180 NX60ZYFCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkXDNE42KM7:TR?= MmTvO|IhcA>? NIL1fIVFVVOR M13DbmlEPTB;MTFOwG0> MmKzNlYyOzZ4OES=
SW948 MknnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlXwNE42KM7:TR?= MojiO|IhcA>? M2LMb2ROW09? MWPJR|UxRTFizszN MUWyOlE{PjZ6NB?=
HCT15 Mli4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWiwMlUh|ryP M2PmXlczKGh? NUP2Z21nTE2VTx?= MWHJR|UxRDBwNDFOwG0> NXfuSmtZOjZzM{[2PFQ>
DLD-1 NV\pV2p3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX2wMlUh|ryP NW\1XmhSPzJiaB?= MULEUXNQ NWPKSYoxUUN3MEywMlgh|ryP Mle2NlYyOzZ4OES=
MIP-101 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{jJSFAvPSEQvF2= NYT3N4N[PzJiaB?= MWLEUXNQ NHXLPG9KSzVyPUGg{txO MlH4NlYyOzZ4OES=
SNU1544 NGHzNIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLwO41oOC53IN88US=> MnuzO|IhcA>? NGXydGRFVVOR NFHOdYxKSzVyPUGg{txO MWKyOlE{PjZ6NB?=
OCI-Ly10 NXnYZoI3S3m2b4TvfIlkKEG|c3H5 M2jSN|czKGh? MUXEUXNQ M2fVcmlEPTB;MD6wOVgh|ryP MUCyOVg4QDN|MR?=
SU-DHL2 NHy2dXhEgXSxdH;4bYMhSXO|YYm= NYH0VmZZPzJiaB?= NHjr[o5FVVOR NFzkRo9KSzVyPUCuNFEh|ryP NXfGbop5OjV6N{izN|E>
OCI-LY7 NV75U4t1S3m2b4TvfIlkKEG|c3H5 MojMO|IhcA>? MYTEUXNQ NYHodFRJUUN3ME2wMlA5OSEQvF2= M2fVT|I2QDd6M{Ox
SU-DHL6 M3m4[2N6fG:2b4jpZ{BCe3OjeR?= NF[yOnI4OiCq Mn:0SG1UVw>? MkDyTWM2OD1yLkS4NkDPxE1? NXrH[Wc2OjV6N{izN|E>
Jeko-1 MVzDfZRwfG:6aXOgRZN{[Xl? MYK3NkBp MnG0SG1UVw>? MmXITWM2OD1yLkCyPUDPxE1? NWPUdYdEOjV6N{izN|E>
JVM-2 MkDNR5l1d3SxeHnjJGF{e2G7 NG\udYU4OiCq MknXSG1UVw>? NVrHNY5YUUN3ME2wMlAyKM7:TR?= MlL2NlU5Pzh|M{G=
Rec-1 MUXDfZRwfG:6aXOgRZN{[Xl? NVjpcZoxPzJiaB?= NVjtOnFTTE2VTx?= MXzJR|UxRTBwMEi3JO69VQ>? Mn\mNlU5Pzh|M{G=
Z-138 NHnDV3BEgXSxdH;4bYMhSXO|YYm= NUjFNYZuPzJiaB?= NGTGOolFVVOR NILSXlNKSzVyPUCuNFE{KM7:TR?= MXiyOVg4QDN|MR?=
H9 NV7qbHFxS3m2b4TvfIlkKEG|c3H5 MYW3NkBp MUXEUXNQ NWDE[2FkUUN3ME2wMlYh|ryP MXeyOVg4QDN|MR?=
HH NXjQNYp7S3m2b4TvfIlkKEG|c3H5 NFfFW3Q4OiCq M{\ieWROW09? M2XEeGlEPTB;MD63JO69VQ>? Ml7FNlU5Pzh|M{G=
DND41 NUjNSWg3S3m2b4TvfIlkKEG|c3H5 MkXlO|IhcA>? NVjhc4JyTE2VTx?= NEK1NWRKSzVyPUCuNUDPxE1? M{fNbFI2QDd6M{Ox
CCL119 MlOzR5l1d3SxeHnjJGF{e2G7 MYO3NkBp NV71[G93TE2VTx?= MXnJR|UxRTBwME[yJO69VQ>? MW[yOVg4QDN|MR?=
J.Cam 1.6 MVXDfZRwfG:6aXOgRZN{[Xl? NInFSXY4OiCq M2LxTWROW09? M4HnPGlEPTB;MD6xNFUh|ryP MlrINlU5Pzh|M{G=
Sup-T1 MYTDfZRwfG:6aXOgRZN{[Xl? MV:3NkBp NX7ocXJzTE2VTx?= NYGwVnJkUUN3ME2yMlE1OiEQvF2= M1niTlI2QDd6M{Ox
Tib 152 M4fZcmN6fG:2b4jpZ{BCe3OjeR?= MV23NkBp NVzPWIFpTE2VTx?= NIqzWnNKSzVyPUCuPEDPxE1? M{PtclI2QDd6M{Ox
MCF7 MXzGeY5kfGmxbjDBd5NigQ>? NEi4fmM2KM7:TR?= MmjHNlQhcA>? M3HHVmROW09? MmPWTY5lfWOnczDHNk9OKGG{cnXzeC=> M4jhd|I2QDN2NECx
MDA-MB-231 MWLGeY5kfGmxbjDBd5NigQ>? MWK1JO69VQ>? MojvNlQhcA>? M2rOWWROW09? MYjJcoR2[2W|IFezM20h[XK{ZYP0 MVSyOVg{PDRyMR?=
MCF7 MoD0SpVv[3Srb36gRZN{[Xl? NFjDPJQ2KM7:TR?= NUTVd|BHOjRiaB?= MojDSG1UVw>? MlHySIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET|EwS0SFMh?= Mmr5NlU5OzR2MEG=
MCF7 NH;SdJRHfW6ldHnvckBCe3OjeR?= NFXHbGU2KM7:TR?= NVPa[|h7OjRiaB?= NHi4TVFFVVOR M3yxRWRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz M3LMW|I2QDN2NECx
MCF7 M{XKPGZ2dmO2aX;uJGF{e2G7 NUfFdXVyPSEQvF2= NVn2Rpc5OjRiaB?= M{XUN2ROW09? M4W0WWRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG= M1r6WlI2QDN2NECx
MCF7 MoXxSpVv[3Srb36gRZN{[Xl? NH3ONos2KM7:TR?= NWT0VpZiOjRiaB?= M{SzUWROW09? NXvPRpNyUW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJJAzOSCZYX[xM2NqeDF? MnvzNlU5OzR2MEG=
MCF7 M4XMc2Z2dmO2aX;uJGF{e2G7 MkfmOUDPxE1? NYrx[2hpOjRiaB?= MXHEUXNQ MkHtTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyO{BMcXBz M3L4e|I2QDN2NECx
MDA-MB-231 NEXDdYhHfW6ldHnvckBCe3OjeR?= Mnv6OUDPxE1? NIXKWVgzPCCq MWDEUXNQ M{\udWRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsyN0OGQ{K= Mln0NlU5OzR2MEG=
MDA-MB-231 M4\ZcWZ2dmO2aX;uJGF{e2G7 NEXLRmUyKM7:TR?= NYXvXXJ7OjRiaB?= NIC1c5FFVVOR M4TXOmlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz NIXFTFYzPTh|NESwNS=>
MDA-MB-231 MnvzSpVv[3Srb36gRZN{[Xl? M{[2UVUh|ryP NH\te2czPCCq M37vTWROW09? MmHiSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIHP5Z4xqdiCEMR?= NGKzNJUzPTh|NESwNS=>
MDA-MB-231 MXfGeY5kfGmxbjDBd5NigQ>? MnvSOUDPxE1? MonSNlQhcA>? MnPMSG1UVw>? MnLaTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> Mn\QNlU5OzR2MEG=
MDA-MB-231 M4TKNGZ2dmO2aX;uJGF{e2G7 Mn\EOUDPxE1? Mk\hNlQhcA>? Mm[xSG1UVw>? MlvJTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyO{BMcXBz MXeyOVg{PDRyMR?=
MDA-MB-231 NGTvUHZHfW6ldHnvckBCe3OjeR?= NHXsPHg2KM7:TR?= Mk\JNlQhcA>? MYrEUXNQ M3n5U2lv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwOVM> NHTSZY8zPTh|NESwNS=>
MCF7 MWTBdI9xfG:|aYOgRZN{[Xl? M1rFZ|Uh|ryP M33TZVI1KGh? M3;WZmROW09? NVP4OY5OUW6mdXPld{BieG:ydH;0bYMh\GWjdHi= NVXBbnlKOjV6M{S0NFE>
MDA-MB-231 MVjBdI9xfG:|aYOgRZN{[Xl? NVPi[2VGPSEQvF2= M{jhUFI1KGh? NWHTWnk5TE2VTx?= MULJcoR2[2W|IHHwc5B1d3SrYzDk[YF1cA>? NEDPeGgzPTh|NESwNS=>
MCF7 NGLa[olHfW6ldHnvckBCe3OjeR?= Ml;jNUDPxE1? MWm3NkBp NETQTWtFVVOR NH:4ZpZKdmS3Y3XzJIF2fG:yaHHnbYMh\GWjdHi= M1flVlI2QDN2NECx
MDA-MB-231 MXXGeY5kfGmxbjDBd5NigQ>? MoTPNUDPxE1? NX\s[4NLPzJiaB?= NF3WUmtFVVOR MX7JcoR2[2W|IHH1eI9xcGGpaXOg[IVifGh? NITXNYgzPTh|NESwNS=>
U-2 OS NUTETVl6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NILqNXQ2OCEQvF2= MXyyOEBp NWj0V4RGTE2VTx?= MXvJR|UxRTF4Lk[g{txO Mn7HNlU4QTJ6MUG=
MG-63 NYm2[GV7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NG\uOW42OCEQvF2= MnTvNlQhcA>? NEP3eIdFVVOR MU\JR|UxRTlwNTFOwG0> Mkm4NlU4QTJ6MUG=
U-2 OS MoTJRZBweHSxc3nzJGF{e2G7 NVTwbo52PSEQvF2= M37UcVI1KGh? NHr2OnFFVVOR MnXBTY5lfWOnczDhdI9xfG:2aXOgZ4VtdCCmZXH0bC=> MVqyOVc6OjhzMR?=
MG-63 NIK2bI9CeG:ydH;zbZMhSXO|YYm= NWDHcY9XPSEQvF2= M2PJUVI1KGh? NUjidWV3TE2VTx?= M{PCeGlv\HWlZYOgZZBweHSxdHnjJINmdGxiZHXheIg> M4\We|I2Pzl{OEGx
U-2 OS NVjPRlNGTnWwY4Tpc44hSXO|YYm= NXT6V4RDPSEQvF2= MViyOEBp NFL1dWtFVVOR NWX6XnVyWHKxbX;0[ZMh[XW2b4DoZYdq[yClZXzsJIRm[XSq NU\EZow2OjV5OUK4NVE>
MG-63 M{\x[mZ2dmO2aX;uJGF{e2G7 MojJOUDPxE1? NHzQTYUzPCCq M1\qWWROW09? MmDwVJJwdW:2ZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp NXGyflA4OjV5OUK4NVE>
PANC-1 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHudpY2OCEQvF2= MWWyOEBp NGjtR|FFVVOR NXmzTpdPUUN3ME23MlEh|ryP M1ntS|I2PjN{MkK1
BxPC-3 NHfLbGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XBXFUxKM7:TR?= MoK4NlQhcA>? NFTyc25FVVOR MWrJR|UxRTZwODFOwG0> NHi0NVQzPTZ|MkKyOS=>
PANC-1 MmnpSpVv[3Srb36gRZN{[Xl? MnTHOUDPxE1? MoTsNlQhcA>? MnXySG1UVw>? MYHJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2IHnuJGczN01icHjhd4U> M4DZXlI2PjN{MkK1
BxPC-3 NXPmXW4zTnWwY4Tpc44hSXO|YYm= NF;iZWQ2KM7:TR?= M1rKWVI1KGh? NGHlW5pFVVOR MorQTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dDDpckBIOi:PIIDoZZNm NYnxb|JlOjV4M{KyNlU>
PANC-1 M3fxR2Z2dmO2aX;uJGF{e2G7 M2HQZ|Uh|ryP MXqyOEBp M2LNXmROW09? MVnJcoR2[2W|IHH1eI9xcGGpaXOgZ4VtdCCmZXH0bC=> NEP6V2MzPTZ|MkKyOS=>
BxPC-3 NGHh[HlHfW6ldHnvckBCe3OjeR?= MkSyOUDPxE1? NXfqbYdtOjRiaB?= NY\4WpJITE2VTx?= MW\JcoR2[2W|IHH1eI9xcGGpaXOgZ4VtdCCmZXH0bC=> MVGyOVY{OjJ{NR?=
SKOV3 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUPwcXF6OTByIN88US=> NELZe4kzPCCq NXjJU2M{TE2VTx?= M1;6PGlEPTB;MkCuOFgh|ryP MkG0NlU3OjR5NUC=
OVCAR4 NU\2PIxNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUOxNFAh|ryP MUKyOEBp MlW1SG1UVw>? NWn4d4tOUUN3ME2yNk4yOyEQvF2= MkTBNlU3OjR5NUC=
SKOV3 NVTzd4lYTnWwY4Tpc44hSXO|YYm= Mlu5OUDPxE1? NIDZO284OiCq MnHoSG1UVw>? NIjKUmlKdmS3Y3XzJGczN01iYYLy[ZN1 MV[yOVYzPDd3MB?=
OVCAR4 NH:ybm9HfW6ldHnvckBCe3OjeR?= MXK1JO69VQ>? MWe3NkBp M{j0UWROW09? NEHDPYJKdmS3Y3XzJGczN01iYYLy[ZN1 MYiyOVYzPDd3MB?=
SKOV3 Mm\QRZBweHSxc3nzJGF{e2G7 MVO1JO69VQ>? MnXkNlQhcA>? M17uS2ROW09? MlPhTY5lfWOnczDhdI9xfG:|aYO= M4P4[VI2PjJ2N{Ww
OVCAR4 NIjQeW1CeG:ydH;zbZMhSXO|YYm= MlW3OUDPxE1? NIPSdlAzPCCq MYnEUXNQ NG\VUnRKdmS3Y3XzJIFxd3C2b4Ppdy=> NH72RW8zPTZ{NEe1NC=>
AGS MnnYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDURYQzPSEQvF2= MoHwNlQhcA>? NIPibGpFVVOR NXrwdWJUUUN3ME2xPU4xQSEQvF2= NVT2[2dHOjV4MEm5NlM>
NCI-N78 NIraNoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXKyOUDPxE1? MnvoNlQhcA>? MnTJSG1UVw>? M4K4VGlEPTB;Mk[uN|Mh|ryP MnPUNlU3ODl7MkO=
AGS NHPDZolCeG:ydH;zbZMhSXO|YYm= NHjxU3k2KM7:TR?= MnXYNlQhcA>? MUnEUXNQ NITXcG9KdmS3Y3XzJIFxd3C2b4Ppdy=> M13SN|I2PjB7OUKz
NCI-N78 NEfRPVZCeG:ydH;zbZMhSXO|YYm= NVzQdYw2PSEQvF2= MkjyNlQhcA>? NUDFNFZiTE2VTx?= MVzJcoR2[2W|IHHwc5B1d3Orcx?= NXrOVXlKOjV4MEm5NlM>
AGS MVrGeY5kfGmxbjDBd5NigQ>? MWG1JO69VQ>? NGXObJMzPCCq NW\O[3lQTE2VTx?= M4rXUWlv\HWlZYOgeIhmKGG3dH;wbIFogQ>? NE\GdIkzPTZyOUmyNy=>
NCI-N78 NXX4VmFoTnWwY4Tpc44hSXO|YYm= Mn[0OUDPxE1? M{nqTFI1KGh? MYjEUXNQ M4fiRWlv\HWlZYOgeIhmKGG3dH;wbIFogQ>? M3rjRVI2PjB7OUKz
HSC-3 NX\C[JU3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml7WNUDPxE1? NHT1WpI1QCCq NYSxXYtWUUN3ME2wMlU1KM7:TR?= M{LYc|I2OzZ4MUSz
GB30 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1vmOFEh|ryP MXu3JIQ> NFTtXWJFVVOR MVzJR|UxRTBwMEGxJO69VQ>? MkO0NlUyODZ2Mki=
GB9 NWfYNmhxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoPSNUDPxE1? MU[3JIQ> M3uzSGROW09? NEjFRXBKSzVyPUCuNFI1KM7:TR?= MVuyOVExPjR{OB?=
GB169 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MljpNUDPxE1? NIT2WXQ4KGR? NWfqe|R3TE2VTx?= NXTRSZpuUUN3ME2wMlA{OiEQvF2= M2DSV|I2OTB4NEK4
T24 M1nOfGZ2dmO2aX;uJGF{e2G7 NIHuNGIyKM7:TR?= NIfIVXE1QCCq NVPXb4Z[TE2VTx?= M2[zVWlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= MnfxNlM1ODN4M{O=
RT4 M2nIOGZ2dmO2aX;uJGF{e2G7 NWX0U41kOSEQvF2= NHTnVWs1QCCq M3npUWROW09? MVnJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2 MlLUNlM1ODN4M{O=
UM-UC-3 MlnPSpVv[3Srb36gRZN{[Xl? M3;qNVEh|ryP MoXyOFghcA>? Mk\CSG1UVw>? NV3weFd7UW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> M2GxTVI{PDB|NkOz
T24 NVvuUmhjSXCxcITvd4l{KEG|c3H5 MX:zMlE3KM7:TR?= MlnWPVYhcA>? NXXyPHJRTE2VTx?= NEKwR3lKSzVyPUCuNFMxPiEQvF2= MoXGNlM1ODN4M{O=
RT4 NV7xe5lGSXCxcITvd4l{KEG|c3H5 M4DGS|MvOTZizszN MojuPVYhcA>? MXTEUXNQ NF\nWJlKSzVyPUCuNVE6QCEQvF2= M1H2dFI{PDB|NkOz
UM-UC-3 NIjs[WJCeG:ydH;zbZMhSXO|YYm= NYG1U3RvOy5zNjFOwG0> MlPJPVYhcA>? NEfMdnBFVVOR Mn76TWM2OD1yLkC0OFkh|ryP M3f3Z|I{PDB|NkOz
OVCAR-5 M4jwcWZ2dmO2aX;uJGF{e2G7 Mnv5OVAhdk1? NX;JcZFpUW6qaXLpeJMh[2WubDDtbYdz[XSrb36= MlvYNlM{OzR|Mke=
SKOV3ip2 NUXKbIRyTnWwY4Tpc44hSXO|YYm= M1q0NFUxKG6P MYXJcohq[mm2czDj[YxtKG2rZ4LheIlwdg>? NXfKbHN2OjN|M{SzNlc>
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MOLT-4 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfaZolTOTBizszN NET1VFU6PiCq NVzIW3h[UUN3ME2wMlAzPiEQvF2= NETUeFEzODFyOEOzPC=>
CCRF-CEM MojaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXxd5JmOTBizszN MWi5OkBp MY\JR|UxRTBwMEm0JO69VQ>? MlzLNlAyODh|M{i=
Kasumi-1 M{mxcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUCxNEDPxE1? NHLPRpU6PiCq MYrJR|UxRTBwMUCzJO69VQ>? NUPRdHg6OjBzMEizN|g>
Karpas-299 NHzVdmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXm5cYpmOTBizszN M2LzS|k3KGh? NID1[m9KSzVyPUCuNFM5KM7:TR?= NXvMVXFSOjBzMEizN|g>
Ramos-RA1 NFHkZ4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHToSYgyOCEQvF2= MnXEPVYhcA>? M3PNOGlEPTB;MD6xNlch|ryP NFPxXoIzODFyOEOzPC=>

... 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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