Alisertib (MLN8237)

Alisertib (MLN8237)は一種の選択性オーロラ(Aurora )A阻害剤で、無細胞試験でIC50値が1.2 nMです。Alisertib (MLN8237)はオーロラAに作用する選択性はオーロラ Bに作用する選択性より200倍以上が高くなります。臨床3期。

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Alisertib (MLN8237) 化学構造
分子量: 518.92

高品質保証

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カスタマーフィードバック(10)

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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)は一種の選択性オーロラ(Aurora )A阻害剤で、無細胞試験でIC50値が1.2 nMです。Alisertib (MLN8237)はオーロラAに作用する選択性はオーロラ Bに作用する選択性より200倍以上が高くなります。臨床3期。
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 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYrzVJoyOC53IN88US=> MXy3NkBp NXzlXWttTE2VTx?= NUPCOJVUUUN3ME2wMlA1KM7:TR?= NV;UfWpQOjZzM{[2PFQ>
LS174T MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGOwdW4xNjVizszN NVLBTWVKPzJiaB?= NYDzTXg2TE2VTx?= NI\XbYZKSzVyPUCuNFUh|ryP M{PndFI3OTN4Nki0
T84 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1ywZlAvPSEQvF2= M17WflczKGh? MX7EUXNQ M2\xR2lEPTB;MD6wPUDPxE1? MWmyOlE{PjZ6NB?=
LS180 NGDCXFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUewMlUh|ryP NYG5SngzPzJiaB?= NF7mPXJFVVOR M1u0S2lEPTB;MTFOwG0> M4rzOFI3OTN4Nki0
SW948 NHrSenpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUewMlUh|ryP MnTTO|IhcA>? MX3EUXNQ M3\WVGlEPTB;MTFOwG0> NUPDRmtQOjZzM{[2PFQ>
HCT15 NYDVSWRJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4q5[|AvPSEQvF2= NH3kSGk4OiCq MmPSSG1UVw>? MYfJR|UxRDBwNDFOwG0> MUOyOlE{PjZ6NB?=
DLD-1 MmHGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH;SOIgxNjVizszN MmnJO|IhcA>? MWLEUXNQ MkCyTWM2ODxyLkig{txO NX7NfHpiOjZzM{[2PFQ>
MIP-101 NVuzfWxGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWf1dpVOOC53IN88US=> MUO3NkBp NWPz[GlvTE2VTx?= MlrpTWM2OD1zIN88US=> MoTXNlYyOzZ4OES=
SNU1544 NILKSYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkfjNE42KM7:TR?= NEfr[WQ4OiCq MmrjSG1UVw>? NH[x[IFKSzVyPUGg{txO M2rve|I3OTN4Nki0
OCI-Ly10 M2jiUGN6fG:2b4jpZ{BCe3OjeR?= NGnO[pI4OiCq NUfJ[WJWTE2VTx?= MUPJR|UxRTBwMEW4JO69VQ>? M4PEbVI2QDd6M{Ox
SU-DHL2 NHfHdGdEgXSxdH;4bYMhSXO|YYm= NYPNVlJPPzJiaB?= MnTYSG1UVw>? MVvJR|UxRTBwMEGg{txO NIDHU3QzPTh5OEOzNS=>
OCI-LY7 MlewR5l1d3SxeHnjJGF{e2G7 M2K5TlczKGh? NU\BPWkxTE2VTx?= MmfYTWM2OD1yLkC4NUDPxE1? NHPKdGczPTh5OEOzNS=>
SU-DHL6 NYrxVG1rS3m2b4TvfIlkKEG|c3H5 MYm3NkBp NFjrbnpFVVOR M4ixN2lEPTB;MD60PFIh|ryP M37tfFI2QDd6M{Ox
Jeko-1 MoDTR5l1d3SxeHnjJGF{e2G7 NY\qO5lGPzJiaB?= NFnReY9FVVOR Mlu0TWM2OD1yLkCyPUDPxE1? M2PLUlI2QDd6M{Ox
JVM-2 MYPDfZRwfG:6aXOgRZN{[Xl? NFPl[3E4OiCq NHradlRFVVOR MX\JR|UxRTBwMEGg{txO MnPZNlU5Pzh|M{G=
Rec-1 M2q1TWN6fG:2b4jpZ{BCe3OjeR?= NF:yelM4OiCq M2PzXmROW09? MVnJR|UxRTBwMEi3JO69VQ>? M4L4WFI2QDd6M{Ox
Z-138 MVrDfZRwfG:6aXOgRZN{[Xl? NXfaZ2IzPzJiaB?= NYrBWphITE2VTx?= MnvqTWM2OD1yLkCxN{DPxE1? Mm\RNlU5Pzh|M{G=
H9 M2m5UWN6fG:2b4jpZ{BCe3OjeR?= NXjFPZBkPzJiaB?= NF[4b5FFVVOR NHHCPHZKSzVyPUCuOkDPxE1? NVrodI9iOjV6N{izN|E>
HH MV\DfZRwfG:6aXOgRZN{[Xl? MmPnO|IhcA>? NEfqW5dFVVOR MmPmTWM2OD1yLkeg{txO M1jyc|I2QDd6M{Ox
DND41 NUDVboE6S3m2b4TvfIlkKEG|c3H5 M3nleFczKGh? M4TOU2ROW09? M3\YV2lEPTB;MD6xJO69VQ>? MkDmNlU5Pzh|M{G=
CCL119 MYfDfZRwfG:6aXOgRZN{[Xl? NIr0WmE4OiCq NVm4N2VpTE2VTx?= M1PmVmlEPTB;MD6wOlIh|ryP Mke2NlU5Pzh|M{G=
J.Cam 1.6 MnHrR5l1d3SxeHnjJGF{e2G7 NYSxVGlGPzJiaB?= NVzPTIc3TE2VTx?= Ml;4TWM2OD1yLkGwOUDPxE1? MVGyOVg4QDN|MR?=
Sup-T1 NXnJUlUzS3m2b4TvfIlkKEG|c3H5 MVy3NkBp MV;EUXNQ NGHxT2JKSzVyPUKuNVQzKM7:TR?= MUSyOVg4QDN|MR?=
Tib 152 NWG3U5AyS3m2b4TvfIlkKEG|c3H5 Mn;XO|IhcA>? NXTKRlZPTE2VTx?= NFvyVZRKSzVyPUCuPEDPxE1? Mm\RNlU5Pzh|M{G=
MCF7 M{flbWZ2dmO2aX;uJGF{e2G7 M2LVTFUh|ryP MkDGNlQhcA>? NHvINnZFVVOR MV;JcoR2[2W|IFeyM20h[XK{ZYP0 NF22OFkzPTh|NESwNS=>
MDA-MB-231 NYLsdpl5TnWwY4Tpc44hSXO|YYm= NXXBZ25SPSEQvF2= NIfuPFQzPCCq MlzySG1UVw>? NWnMcZh4UW6mdXPld{BIOy:PIHHydoV{fA>? M37nV|I2QDN2NECx
MCF7 MXzGeY5kfGmxbjDBd5NigQ>? NEjTPZk2KM7:TR?= Ml31NlQhcA>? NGLzTnRFVVOR MWfE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNU9ETEN{ NX\1SVZWOjV6M{S0NFE>
MCF7 NVu1Z4RSTnWwY4Tpc44hSXO|YYm= MojEOUDPxE1? MVWyOEBp MkDtSG1UVw>? NYjORphMTGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzJ? NFjxN3ozPTh|NESwNS=>
MCF7 NYX0cWZWTnWwY4Tpc44hSXO|YYm= M{PTcFUh|ryP NWfwZ3RsOjRiaB?= MoqwSG1UVw>? M4DwTGRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG= M2T2[|I2QDN2NECx
MCF7 Mlr0SpVv[3Srb36gRZN{[Xl? MonDOUDPxE1? NGPifXUzPCCq MkfiSG1UVw>? NIDsV|RKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFIyKFejZkGvR4lxOQ>? NGm5[JczPTh|NESwNS=>
MCF7 MYjGeY5kfGmxbjDBd5NigQ>? NF7Oe2g2KM7:TR?= MoTXNlQhcA>? M1y0fGROW09? MVXJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF? NIrE[GIzPTh|NESwNS=>
MDA-MB-231 MXPGeY5kfGmxbjDBd5NigQ>? M2\PdlUh|ryP M17RSVI1KGh? NH7pW21FVVOR NUTzWoZOTGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=> MlO5NlU5OzR2MEG=
MDA-MB-231 NYX3Wmg4TnWwY4Tpc44hSXO|YYm= NELlepEyKM7:TR?= MlPUNlQhcA>? M4XRTWROW09? NHLNV4FKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOg>? NH7lbWUzPTh|NESwNS=>
MDA-MB-231 NETLcWlHfW6ldHnvckBCe3OjeR?= MnfWOUDPxE1? M3;LUlI1KGh? NYDKSIlETE2VTx?= Mn3MSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIHP5Z4xqdiCEMR?= NHnXSXgzPTh|NESwNS=>
MDA-MB-231 M1rwNmZ2dmO2aX;uJGF{e2G7 MVS1JO69VQ>? NWfoOopGOjRiaB?= M1Lhd2ROW09? M1vOVGlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlEhX2GoMT;DbZAy NFXCUW4zPTh|NESwNS=>
MDA-MB-231 MlvNSpVv[3Srb36gRZN{[Xl? NHPXdYs2KM7:TR?= NIrrR2wzPCCq MX3EUXNQ M37JbWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?= MYKyOVg{PDRyMR?=
MDA-MB-231 MnXPSpVv[3Srb36gRZN{[Xl? MVq1JO69VQ>? NFS0N20zPCCq NHH5WmtFVVOR NVKwNXNzUW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJJA2Ow>? MlztNlU5OzR2MEG=
MCF7 NXfGe|dmSXCxcITvd4l{KEG|c3H5 NFLYTFQ2KM7:TR?= MkLRNlQhcA>? MWHEUXNQ M{SwcWlv\HWlZYOgZZBweHSxdHnjJIRm[XSq NXLyOHJtOjV6M{S0NFE>
MDA-MB-231 NEjYS4pCeG:ydH;zbZMhSXO|YYm= MmXyOUDPxE1? M1rQO|I1KGh? MmPJSG1UVw>? MlfvTY5lfWOnczDhdI9xfG:2aXOg[IVifGh? MYKyOVg{PDRyMR?=
MCF7 M4exXWZ2dmO2aX;uJGF{e2G7 NWPB[4RXOSEQvF2= NG\2NYM4OiCq MYjEUXNQ MXHJcoR2[2W|IHH1eI9xcGGpaXOg[IVifGh? M3LUflI2QDN2NECx
MDA-MB-231 NFz4e|JHfW6ldHnvckBCe3OjeR?= MmTZNUDPxE1? NGLrfHU4OiCq MUjEUXNQ NWjVcI5sUW6mdXPld{BifXSxcHjh[4lkKGSnYYTo M{G0VVI2QDN2NECx
U-2 OS MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1PIOlUxKM7:TR?= NE\rSWkzPCCq NHztRXpFVVOR MX3JR|UxRTF4Lk[g{txO M1PPSlI2Pzl{OEGx
MG-63 NFW0XFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jSWlUxKM7:TR?= M376d|I1KGh? M4H1SWROW09? MX7JR|UxRTlwNTFOwG0> MVqyOVc6OjhzMR?=
U-2 OS NGnGUXFCeG:ydH;zbZMhSXO|YYm= MUS1JO69VQ>? NHfKTJQzPCCq NF3vTVRFVVOR NYrZVHdUUW6mdXPld{BieG:ydH;0bYMh[2WubDDk[YF1cA>? MXSyOVc6OjhzMR?=
MG-63 M{jFdGFxd3C2b4Ppd{BCe3OjeR?= MlzZOUDPxE1? NUnvPHlxOjRiaB?= M4DhRWROW09? M1;2[Glv\HWlZYOgZZBweHSxdHnjJINmdGxiZHXheIg> NXi5WIY5OjV5OUK4NVE>
U-2 OS MlLXSpVv[3Srb36gRZN{[Xl? MXy1JO69VQ>? M2HoOlI1KGh? NIe5O2dFVVOR MXrQdo9ud3SnczDheZRweGijZ3njJINmdGxiZHXheIg> MWCyOVc6OjhzMR?=
MG-63 M1X2b2Z2dmO2aX;uJGF{e2G7 NESyOHU2KM7:TR?= M4PyXFI1KGh? NXPsXIhHTE2VTx?= MVvQdo9ud3SnczDheZRweGijZ3njJINmdGxiZHXheIg> MY[yOVc6OjhzMR?=
PANC-1 M4WxNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2HrW|UxKM7:TR?= MX[yOEBp MUXEUXNQ MV;JR|UxRTdwMTFOwG0> NGLFWI0zPTZ|MkKyOS=>
BxPC-3 NXfvUngzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTQVmo2OCEQvF2= MXOyOEBp M1rLUGROW09? NEPSOFlKSzVyPU[uPEDPxE1? Mly0NlU3OzJ{MkW=
PANC-1 NXn2O|l5TnWwY4Tpc44hSXO|YYm= NF;Nbmk2KM7:TR?= M4LsSVI1KGh? M136RWROW09? MX;JcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2IHnuJGczN01icHjhd4U> MXOyOVY{OjJ{NR?=
BxPC-3 MYTGeY5kfGmxbjDBd5NigQ>? MVq1JO69VQ>? NIO2[2YzPCCq MVHEUXNQ Mn36TY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dDDpckBIOi:PIIDoZZNm MmnhNlU3OzJ{MkW=
PANC-1 NH;qZolHfW6ldHnvckBCe3OjeR?= MkjYOUDPxE1? MkLENlQhcA>? NGjEO5lFVVOR NWPlbXZCUW6mdXPld{BifXSxcHjh[4lkKGOnbHyg[IVifGh? M3XPVVI2PjN{MkK1
BxPC-3 NXHY[lhsTnWwY4Tpc44hSXO|YYm= NYL3R5dNPSEQvF2= NITZW3EzPCCq MlKwSG1UVw>? M2PyZmlv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp M1KxOFI2PjN{MkK1
SKOV3 MlPwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkmzNVAxKM7:TR?= MlzENlQhcA>? MWTEUXNQ NUnnd3NIUUN3ME2yNE41QCEQvF2= M1XKT|I2PjJ2N{Ww
OVCAR4 NW\RXFM1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2T3O|ExOCEQvF2= NV[2NoRkOjRiaB?= NGLEbHlFVVOR M2HoeGlEPTB;MkKuNVMh|ryP MV[yOVYzPDd3MB?=
SKOV3 MXHGeY5kfGmxbjDBd5NigQ>? NGTF[5U2KM7:TR?= MnzxO|IhcA>? MoHFSG1UVw>? MlXtTY5lfWOnczDHNk9OKGG{cnXzeC=> M4ixZlI2PjJ2N{Ww
OVCAR4 NIDPc|RHfW6ldHnvckBCe3OjeR?= MVO1JO69VQ>? MXO3NkBp MWDEUXNQ NVfZSYx{UW6mdXPld{BIOi:PIHHydoV{fA>? MYeyOVYzPDd3MB?=
SKOV3 M3zaTGFxd3C2b4Ppd{BCe3OjeR?= MYK1JO69VQ>? M{m1fFI1KGh? MVLEUXNQ NXzJNoU6UW6mdXPld{BieG:ydH;zbZM> NUHCfVlHOjV4MkS3OVA>
OVCAR4 MUHBdI9xfG:|aYOgRZN{[Xl? NGTFZ3k2KM7:TR?= MmfmNlQhcA>? NHLUR5lFVVOR Mly5TY5lfWOnczDhdI9xfG:|aYO= NVLDPXV{OjV4MkS3OVA>
AGS NU[2SmNkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYT2OIZbOjVizszN NY[zOllzOjRiaB?= NUTqXFU3TE2VTx?= NYDw[oNxUUN3ME2xPU4xQSEQvF2= MoDPNlU3ODl7MkO=
NCI-N78 NVzBfFhrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoLvNlUh|ryP MVKyOEBp NFzDSmRFVVOR MmXUTWM2OD1{Nj6zN{DPxE1? NXTRTY9bOjV4MEm5NlM>
AGS NIPyTI9CeG:ydH;zbZMhSXO|YYm= MlrhOUDPxE1? NVnKUJFGOjRiaB?= M2DySGROW09? MoGxTY5lfWOnczDhdI9xfG:|aYO= NHPNfIMzPTZyOUmyNy=>
NCI-N78 NI\2N3RCeG:ydH;zbZMhSXO|YYm= M1;ucVUh|ryP NXXtfW82OjRiaB?= M2LDcGROW09? MXzJcoR2[2W|IHHwc5B1d3Orcx?= NGXTZ3IzPTZyOUmyNy=>
AGS MWrGeY5kfGmxbjDBd5NigQ>? NXHpUHpuPSEQvF2= NH20O|UzPCCq MV7EUXNQ NFvYTHNKdmS3Y3XzJJRp\SCjdYTvdIhi\3l? MmO0NlU3ODl7MkO=
NCI-N78 NGqxU3dHfW6ldHnvckBCe3OjeR?= NWfDZ21yPSEQvF2= NVzGe2JjOjRiaB?= MkLCSG1UVw>? MlXNTY5lfWOnczD0bIUh[XW2b4DoZYd6 Ml;FNlU3ODl7MkO=
HSC-3 NGnnSFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEDWeZEyKM7:TR?= MnzoOFghcA>? NHnI[JFKSzVyPUCuOVQh|ryP M4Tt[lI2OzZ4MUSz
GB30 NGD4c29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NES3OlAyKM7:TR?= NHPVOng4KGR? M2Dob2ROW09? MYrJR|UxRTBwMEGxJO69VQ>? MUGyOVExPjR{OB?=
GB9 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoroNUDPxE1? MmDvO{Bl MkfxSG1UVw>? MWXJR|UxRTBwMEK0JO69VQ>? Mn\LNlUyODZ2Mki=
GB169 NYHKRlZLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHiw[VMyKM7:TR?= MWq3JIQ> Ml2xSG1UVw>? NIn1[lhKSzVyPUCuNFMzKM7:TR?= NYLENWc1OjVzME[0Nlg>
T24 NEHTNm9HfW6ldHnvckBCe3OjeR?= NX62OIVuOSEQvF2= MlrIOFghcA>? NGXJU|RFVVOR M17xXmlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= MVuyN|QxOzZ|Mx?=
RT4 MorHSpVv[3Srb36gRZN{[Xl? MofENUDPxE1? NUXCS3UzPDhiaB?= NXfuW21OTE2VTx?= MUjJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2 NUD6blFpOjN2MEO2N|M>
UM-UC-3 NEDBUJZHfW6ldHnvckBCe3OjeR?= M4DPTFEh|ryP MVS0PEBp NHnH[XFFVVOR NVPJTJpmUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> NWPHOmRoOjN2MEO2N|M>
T24 MlvyRZBweHSxc3nzJGF{e2G7 MlHqN{4yPiEQvF2= NWPTOZp{QTZiaB?= MWLEUXNQ NXLuRWdjUUN3ME2wMlA{ODZizszN NWnCZWJXOjN2MEO2N|M>
RT4 M1yySmFxd3C2b4Ppd{BCe3OjeR?= NGjmfYE{NjF4IN88US=> NGTRbWE6PiCq M3O5[WROW09? NEXEfIVKSzVyPUCuNVE6QCEQvF2= NHTWe5AzOzRyM{[zNy=>
UM-UC-3 NV\K[mQ{SXCxcITvd4l{KEG|c3H5 NH23bW0{NjF4IN88US=> MojzPVYhcA>? M1L0bWROW09? M3XJ[mlEPTB;MD6wOFQ6KM7:TR?= NYHBe214OjN2MEO2N|M>
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COG-LL-317 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGPGVYMyOCEQvF2= NHXSdXQ6PiCq NFLteWRKSzVyPUCuNFQ4KM7:TR?= M{\lc|IxOTB6M{O4
RS4-11 NYjxbnhOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2riV|ExKM7:TR?= MV65OkBp NWHMe2I2UUN3ME2wMlAyQCEQvF2= Mnr2NlAyODh|M{i=
MOLT-4 NXvnRWxuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlXMNVAh|ryP MlrjPVYhcA>? NHzodIdKSzVyPUCuNFI3KM7:TR?= NUXGRoFlOjBzMEizN|g>
CCRF-CEM NG\QfmZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmSxNVAh|ryP NGfVXFg6PiCq M2S2[WlEPTB;MD6wPVQh|ryP MYGyNFExQDN|OB?=
Kasumi-1 NWGyN5U{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVSxNEDPxE1? MX:5OkBp NXz4OGJLUUN3ME2wMlExOyEQvF2= M1zxWVIxOTB6M{O4
Karpas-299 M1TkTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPzO48yOCEQvF2= MX[5OkBp M1PaUmlEPTB;MD6wN|gh|ryP NUDMS|NQOjBzMEizN|g>
Ramos-RA1 M1vucWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIrtN3UyOCEQvF2= NGHKbYg6PiCq M3fhS2lEPTB;MD6xNlch|ryP Mmr3NlAyODh|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 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 27 mg/mL (52.03 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
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-

文献中の引用 (46)

Frequently Asked Questions

  • Question 1
    What is the suggested formulation of this compound for mouse injection(i.p.)?

    Answer: It can be dissolved in 6% DMSO/50% PEG 300/5% Tween 80/ddH2O at 10 mg/ml as a clear solution.

技術サポート&よくある質問(FAQ)

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