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(12)

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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 NXrUdlRDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;TOG5bOC53IN88US=> M1P6UlczKGh? NGfpeY9FVVOR MmjETWM2OD1yLkC0JO69VQ>? MYGyOlE{PjZ6NB?=
LS174T MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUiwMlUh|ryP M1XOOVczKGh? M{TWSWROW09? MmDyTWM2OD1yLkC1JO69VQ>? MVyyOlE{PjZ6NB?=
T84 NWPPSG9{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2O0UVAvPSEQvF2= NIHjW4k4OiCq NYKycVVYTE2VTx?= MoPUTWM2OD1yLkC5JO69VQ>? Ml\VNlYyOzZ4OES=
LS180 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEfmeWQxNjVizszN NHHMc|c4OiCq Mn;SSG1UVw>? NF\reINKSzVyPUGg{txO MYeyOlE{PjZ6NB?=
SW948 MoTWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2LBdVAvPSEQvF2= MW[3NkBp MVfEUXNQ NEnJN3NKSzVyPUGg{txO NVXybW42OjZzM{[2PFQ>
HCT15 NIjsOolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmLrNE42KM7:TR?= Mnm2O|IhcA>? MmrQSG1UVw>? NUjXcoN5UUN3MEywMlQh|ryP NYr2S3JxOjZzM{[2PFQ>
DLD-1 M3TSTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUXyZ4FKOC53IN88US=> MWO3NkBp M{O3SWROW09? MlfhTWM2ODxyLkig{txO MkfHNlYyOzZ4OES=
MIP-101 MnPvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWCyWmhuOC53IN88US=> MYm3NkBp MoPRSG1UVw>? NX7P[mx5UUN3ME2xJO69VQ>? NH7Qd3AzPjF|Nk[4OC=>
SNU1544 NEjEWolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXOwMlUh|ryP M4DvclczKGh? MYnEUXNQ NYrUd3FUUUN3ME2xJO69VQ>? NYXPfYNOOjZzM{[2PFQ>
OCI-Ly10 Ml\MR5l1d3SxeHnjJGF{e2G7 M33HRlczKGh? NH7OR|FFVVOR MYfJR|UxRTBwMEW4JO69VQ>? M1zpOlI2QDd6M{Ox
SU-DHL2 NXP3d2p5S3m2b4TvfIlkKEG|c3H5 M1PBblczKGh? NXrqeVUxTE2VTx?= NX7FboloUUN3ME2wMlAyKM7:TR?= MXWyOVg4QDN|MR?=
OCI-LY7 NGTLXXFEgXSxdH;4bYMhSXO|YYm= NFzkWXo4OiCq M4j0TWROW09? MnXlTWM2OD1yLkC4NUDPxE1? NFS2W3kzPTh5OEOzNS=>
SU-DHL6 NWq0fWpwS3m2b4TvfIlkKEG|c3H5 NYe4WGRPPzJiaB?= MUfEUXNQ MWjJR|UxRTBwNEiyJO69VQ>? NEHOdoEzPTh5OEOzNS=>
Jeko-1 NHTDeYJEgXSxdH;4bYMhSXO|YYm= M4LnT|czKGh? MW\EUXNQ MlzLTWM2OD1yLkCyPUDPxE1? M3K5OlI2QDd6M{Ox
JVM-2 MVzDfZRwfG:6aXOgRZN{[Xl? NEDnZWY4OiCq NEnjbYpFVVOR MVvJR|UxRTBwMEGg{txO MV[yOVg4QDN|MR?=
Rec-1 MY\DfZRwfG:6aXOgRZN{[Xl? NV\YdlV4PzJiaB?= MWLEUXNQ MnnYTWM2OD1yLkC4O{DPxE1? NFuyd4szPTh5OEOzNS=>
Z-138 MkfBR5l1d3SxeHnjJGF{e2G7 NYiyeowyPzJiaB?= NH3rRmRFVVOR NIPMc5lKSzVyPUCuNFE{KM7:TR?= M{PwXFI2QDd6M{Ox
H9 M2HESWN6fG:2b4jpZ{BCe3OjeR?= MnjqO|IhcA>? NFn0[FVFVVOR M4nSbWlEPTB;MD62JO69VQ>? M2SwS|I2QDd6M{Ox
HH M37GcGN6fG:2b4jpZ{BCe3OjeR?= NV3HVW1tPzJiaB?= NGTtbWFFVVOR MVnJR|UxRTBwNzFOwG0> NYHae3o2OjV6N{izN|E>
DND41 NH\j[YNEgXSxdH;4bYMhSXO|YYm= MkXXO|IhcA>? MXrEUXNQ MlPSTWM2OD1yLkGg{txO M2H3NVI2QDd6M{Ox
CCL119 NVLkbYJKS3m2b4TvfIlkKEG|c3H5 NYHnOVVJPzJiaB?= NYPRfoZzTE2VTx?= MnjpTWM2OD1yLkC2NkDPxE1? MYKyOVg4QDN|MR?=
J.Cam 1.6 M2qyPGN6fG:2b4jpZ{BCe3OjeR?= MmfOO|IhcA>? MWHEUXNQ NELaUJhKSzVyPUCuNVA2KM7:TR?= M1;h[FI2QDd6M{Ox
Sup-T1 M4XPZWN6fG:2b4jpZ{BCe3OjeR?= MnXTO|IhcA>? NV\HXXRKTE2VTx?= M2\WfmlEPTB;Mj6xOFIh|ryP MX[yOVg4QDN|MR?=
Tib 152 NWnMb3JoS3m2b4TvfIlkKEG|c3H5 M{H5U|czKGh? NEjMU3JFVVOR MWXJR|UxRTBwODFOwG0> MUKyOVg4QDN|MR?=
MCF7 NYH4fY9uTnWwY4Tpc44hSXO|YYm= M3XMeVUh|ryP NXfpbGlQOjRiaB?= MmfaSG1UVw>? MVzJcoR2[2W|IFeyM20h[XK{ZYP0 NHrrNHMzPTh|NESwNS=>
MDA-MB-231 MXTGeY5kfGmxbjDBd5NigQ>? NHuyZ4s2KM7:TR?= MV6yOEBp NHn5OW1FVVOR NX3rdGFOUW6mdXPld{BIOy:PIHHydoV{fA>? NWXLU5N3OjV6M{S0NFE>
MCF7 MYPGeY5kfGmxbjDBd5NigQ>? MmnSOUDPxE1? MUCyOEBp MX;EUXNQ MnPlSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET|EwS0SFMh?= MYOyOVg{PDRyMR?=
MCF7 MXfGeY5kfGmxbjDBd5NigQ>? NYrzdZl4PSEQvF2= Mn;CNlQhcA>? M2OxUmROW09? NXX1T5E2TGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzJ? M4O1ZVI2QDN2NECx
MCF7 MYfGeY5kfGmxbjDBd5NigQ>? MlvYOUDPxE1? MYmyOEBp MYfEUXNQ M4PzNGRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG= MUOyOVg{PDRyMR?=
MCF7 NVi5[JRwTnWwY4Tpc44hSXO|YYm= NWPEZ|dpPSEQvF2= NGH6TI4zPCCq NYS1R4o4TE2VTx?= M1LlVmlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlEhX2GoMT;DbZAy NFPQZXIzPTh|NESwNS=>
MCF7 MnTUSpVv[3Srb36gRZN{[Xl? Mk\SOUDPxE1? M{HDXFI1KGh? NYnwboR4TE2VTx?= NXezbGZ3UW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJJAzPyCNaYCx MlzFNlU5OzR2MEG=
MDA-MB-231 NXPRRY9zTnWwY4Tpc44hSXO|YYm= MlW2OUDPxE1? MYOyOEBp NIPkNo9FVVOR NVK4[ZBQTGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=> NWL6b|VmOjV6M{S0NFE>
MDA-MB-231 MWrGeY5kfGmxbjDBd5NigQ>? M{TRXlEh|ryP NFnjcVgzPCCq NYrxPYhCTE2VTx?= M1zSdWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz M1TmXFI2QDN2NECx
MDA-MB-231 MXrGeY5kfGmxbjDBd5NigQ>? MV21JO69VQ>? NIrhOm8zPCCq NYrkfpI1TE2VTx?= NHLoU25F\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gZ5lkdGmwIFKx Mk\zNlU5OzR2MEG=
MDA-MB-231 NH:1fo9HfW6ldHnvckBCe3OjeR?= NYPSV5RYPSEQvF2= MmfoNlQhcA>? NGrl[mRFVVOR MXLJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEKxJHdi\jFxQ3nwNS=> MoPNNlU5OzR2MEG=
MDA-MB-231 MW\GeY5kfGmxbjDBd5NigQ>? MmTMOUDPxE1? M{PQT|I1KGh? M{PaT2ROW09? NEDqZmVKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFI4KEurcEG= M160SFI2QDN2NECx
MDA-MB-231 MUDGeY5kfGmxbjDBd5NigQ>? NEDycZk2KM7:TR?= M1vrW|I1KGh? NHSwXY9FVVOR NF;VflJKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFU{ NWD1V|RuOjV6M{S0NFE>
MCF7 MkXWRZBweHSxc3nzJGF{e2G7 M4rGW|Uh|ryP Mmm1NlQhcA>? MV;EUXNQ MnvFTY5lfWOnczDhdI9xfG:2aXOg[IVifGh? NVezNpFFOjV6M{S0NFE>
MDA-MB-231 MWTBdI9xfG:|aYOgRZN{[Xl? NIPiVZg2KM7:TR?= MkfWNlQhcA>? Mn;MSG1UVw>? NGPWc5NKdmS3Y3XzJIFxd3C2b4TpZ{Bl\WG2aB?= M4rE[|I2QDN2NECx
MCF7 NXXkOGVyTnWwY4Tpc44hSXO|YYm= MlrnNUDPxE1? MmXTO|IhcA>? MVvEUXNQ Mn[zTY5lfWOnczDheZRweGijZ3njJIRm[XSq MoL3NlU5OzR2MEG=
MDA-MB-231 M1;3eGZ2dmO2aX;uJGF{e2G7 MYCxJO69VQ>? M1f6e|czKGh? M2DaO2ROW09? MWrJcoR2[2W|IHH1eI9xcGGpaXOg[IVifGh? M{LhXlI2QDN2NECx
U-2 OS MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3rKVFUxKM7:TR?= NU\FTlBMOjRiaB?= NUToU5hYTE2VTx?= M{fYWWlEPTB;MU[uOkDPxE1? MmfMNlU4QTJ6MUG=
MG-63 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2HYUlUxKM7:TR?= M4LMRlI1KGh? M{jBSmROW09? NIS4VW5KSzVyPUmuOUDPxE1? NUDUcHZ[OjV5OUK4NVE>
U-2 OS MVXBdI9xfG:|aYOgRZN{[Xl? NGDjVHQ2KM7:TR?= MU[yOEBp M3\TZWROW09? MX;JcoR2[2W|IHHwc5B1d3SrYzDj[YxtKGSnYYTo NIfmR2MzPTd7MkixNS=>
MG-63 M3XwTWFxd3C2b4Ppd{BCe3OjeR?= MojmOUDPxE1? M{Lyd|I1KGh? NEPFNXZFVVOR NWXKW4U2UW6mdXPld{BieG:ydH;0bYMh[2WubDDk[YF1cA>? MUCyOVc6OjhzMR?=
U-2 OS M3rWOGZ2dmO2aX;uJGF{e2G7 M2eyRVUh|ryP MoWyNlQhcA>? M2PiZ2ROW09? MnzCVJJwdW:2ZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp NI[zVoUzPTd7MkixNS=>
MG-63 MljHSpVv[3Srb36gRZN{[Xl? MV:1JO69VQ>? NXTBRoVHOjRiaB?= NHO5[HJFVVOR NXG0fYRLWHKxbX;0[ZMh[XW2b4DoZYdq[yClZXzsJIRm[XSq NHW5VI4zPTd7MkixNS=>
PANC-1 NIL1[m5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoWwOVAh|ryP NHzUeG8zPCCq M{TMbGROW09? NYPlW2VxUUN3ME23MlEh|ryP M3PDXFI2PjN{MkK1
BxPC-3 NETwPHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLvOVAh|ryP M{Xl[VI1KGh? M2C3b2ROW09? NYPDdnZWUUN3ME22Mlgh|ryP MYGyOVY{OjJ{NR?=
PANC-1 MVjGeY5kfGmxbjDBd5NigQ>? NIXLOGI2KM7:TR?= M3;pXlI1KGh? M4\Y[mROW09? Mny4TY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dDDpckBIOi:PIIDoZZNm Ml[xNlU3OzJ{MkW=
BxPC-3 M2fRSmZ2dmO2aX;uJGF{e2G7 MoPFOUDPxE1? MnfZNlQhcA>? M2rneWROW09? Mn;UTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dDDpckBIOi:PIIDoZZNm MVSyOVY{OjJ{NR?=
PANC-1 M12yWGZ2dmO2aX;uJGF{e2G7 MYS1JO69VQ>? MWSyOEBp MkfISG1UVw>? Ml;1TY5lfWOnczDheZRweGijZ3njJINmdGxiZHXheIg> NVnEVlQ6OjV4M{KyNlU>
BxPC-3 MYfGeY5kfGmxbjDBd5NigQ>? NYW5N3VrPSEQvF2= MVeyOEBp NVjs[Zh3TE2VTx?= NGDNTG1KdmS3Y3XzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? M1i3OVI2PjN{MkK1
SKOV3 M3y5[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWniPIZ5OTByIN88US=> MXmyOEBp NFjnTHFFVVOR NUHMN|M3UUN3ME2yNE41QCEQvF2= NWTOUZF{OjV4MkS3OVA>
OVCAR4 MnXNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYqxNFAh|ryP MmjINlQhcA>? NFq2VWJFVVOR MlP3TWM2OD1{Mj6xN{DPxE1? NVXrNYxROjV4MkS3OVA>
SKOV3 NHjYU3FHfW6ldHnvckBCe3OjeR?= NXu2WGdnPSEQvF2= NWmyc3pZPzJiaB?= Mmq4SG1UVw>? NFnUb2xKdmS3Y3XzJGczN01iYYLy[ZN1 M2rTSFI2PjJ2N{Ww
OVCAR4 MmLqSpVv[3Srb36gRZN{[Xl? NGHrWXA2KM7:TR?= NHrsfYg4OiCq NX3BfXBwTE2VTx?= M1KySmlv\HWlZYOgS|IwVSCjcoLld5Q> NV7PfFNTOjV4MkS3OVA>
SKOV3 Mm\qRZBweHSxc3nzJGF{e2G7 NHvpZVA2KM7:TR?= MX2yOEBp NGqxOZJFVVOR NH3yVmhKdmS3Y3XzJIFxd3C2b4Ppdy=> MWeyOVYzPDd3MB?=
OVCAR4 M4jMbWFxd3C2b4Ppd{BCe3OjeR?= NIfJflk2KM7:TR?= NGrYTpUzPCCq MXHEUXNQ MmXhTY5lfWOnczDhdI9xfG:|aYO= MViyOVYzPDd3MB?=
AGS MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXvXV5FyOjVizszN NVHT[nNLOjRiaB?= NF7TVIFFVVOR NHiw[IFKSzVyPUG5MlA6KM7:TR?= MoX2NlU3ODl7MkO=
NCI-N78 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn[4NlUh|ryP Mk\0NlQhcA>? MWjEUXNQ MUDJR|UxRTJ4LkOzJO69VQ>? MojtNlU3ODl7MkO=
AGS NYnodVhlSXCxcITvd4l{KEG|c3H5 NVLxcXBPPSEQvF2= NVnYRWZ2OjRiaB?= NUfPUoNHTE2VTx?= M4XLT2lv\HWlZYOgZZBweHSxc3nz Mo\uNlU3ODl7MkO=
NCI-N78 MknFRZBweHSxc3nzJGF{e2G7 Mmn4OUDPxE1? NEfUcG4zPCCq MWTEUXNQ Mo\CTY5lfWOnczDhdI9xfG:|aYO= NGnKXXQzPTZyOUmyNy=>
AGS MWHGeY5kfGmxbjDBd5NigQ>? NUWwOpNUPSEQvF2= NUDHRYtoOjRiaB?= MWPEUXNQ NXjoSY56UW6mdXPld{B1cGViYYX0c5Bp[We7 NEf3OnozPTZyOUmyNy=>
NCI-N78 M4DFWWZ2dmO2aX;uJGF{e2G7 MXe1JO69VQ>? M{LkbFI1KGh? M{frXWROW09? M4q2T2lv\HWlZYOgeIhmKGG3dH;wbIFogQ>? MnHUNlU3ODl7MkO=
HSC-3 M2TL[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV2xJO69VQ>? NEDkfI41QCCq NV\5WJpCUUN3ME2wMlU1KM7:TR?= Ml61NlU{PjZzNEO=
GB30 NW\admQ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYOxJO69VQ>? NGHqN5Y4KGR? MnzUSG1UVw>? M33UNGlEPTB;MD6wNVEh|ryP NHzHbnAzPTFyNkSyPC=>
GB9 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYLONFNLOSEQvF2= M4K3[Vch\A>? NFXOW4JFVVOR M2j6NmlEPTB;MD6wNlQh|ryP MW[yOVExPjR{OB?=
GB169 NF34XItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUGxJO69VQ>? NWS0UI1CPyCm NFLMT3hFVVOR M2nEUWlEPTB;MD6wN|Ih|ryP MW[yOVExPjR{OB?=
T24 NWLa[phmTnWwY4Tpc44hSXO|YYm= MWCxJO69VQ>? MWK0PEBp MmPvSG1UVw>? MoH3TY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= NUTNbW1vOjN2MEO2N|M>
RT4 M2jMNWZ2dmO2aX;uJGF{e2G7 MUOxJO69VQ>? NG\DclE1QCCq NVX5UIt1TE2VTx?= NYLOUFhPUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> M4D1O|I{PDB|NkOz
UM-UC-3 NHvO[5VHfW6ldHnvckBCe3OjeR?= MoP3NUDPxE1? MnP1OFghcA>? NFLGOWhFVVOR MmTsTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= Mk\3NlM1ODN4M{O=
T24 NGrlN|hCeG:ydH;zbZMhSXO|YYm= NIG2Xog{NjF4IN88US=> NWHBdGlHQTZiaB?= M4PiNWROW09? NFzQZopKSzVyPUCuNFMxPiEQvF2= MY[yN|QxOzZ|Mx?=
RT4 NVr6bWEzSXCxcITvd4l{KEG|c3H5 NXHlcIM1Oy5zNjFOwG0> M1PV[|k3KGh? MWDEUXNQ M4rNW2lEPTB;MD6xNVk5KM7:TR?= MnjKNlM1ODN4M{O=
UM-UC-3 MkSxRZBweHSxc3nzJGF{e2G7 Mm\rN{4yPiEQvF2= MYW5OkBp NIfnUmJFVVOR NHjqOWhKSzVyPUCuNFQ1QSEQvF2= Mk\uNlM1ODN4M{O=
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COG-LL-317 NWDOOJg1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXKxNEDPxE1? NVnYVIFYQTZiaB?= MV3JR|UxRTBwMES3JO69VQ>? MYeyNFExQDN|OB?=
RS4-11 Ml;SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFT0ZZQyOCEQvF2= NX\WV4g5QTZiaB?= MmXFTWM2OD1yLkCxPEDPxE1? NIfRTpUzODFyOEOzPC=>
MOLT-4 NYHFWG5XT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYCxNEDPxE1? NHPrcXA6PiCq MWPJR|UxRTBwMEK2JO69VQ>? M3nufVIxOTB6M{O4
CCRF-CEM NUO2OpdQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPMdGFNOTBizszN M3nTRlk3KGh? M3LCXGlEPTB;MD6wPVQh|ryP MXKyNFExQDN|OB?=
Kasumi-1 M4\4XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHrme|gyOCEQvF2= NFXsZ|E6PiCq NGTuOGlKSzVyPUCuNVA{KM7:TR?= M333[lIxOTB6M{O4
Karpas-299 NUTicIJOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7hPHoyOCEQvF2= M2jUVFk3KGh? NIH4d4xKSzVyPUCuNFM5KM7:TR?= NGLXUI4zODFyOEOzPC=>
Ramos-RA1 MoTzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnCNVAh|ryP MVq5OkBp MV7JR|UxRTBwMUK3JO69VQ>? NHnCTHMzODFyOEOzPC=>

... 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 (48)

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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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