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 Mk[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M32wPFAvPSEQvF2= NVrRTotLPzJiaB?= MXXEUXNQ MUDJR|UxRTBwMESg{txO MWOyOlE{PjZ6NB?=
LS174T NIDMeoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGn4WIIxNjVizszN M{P3SFczKGh? NFzM[mVFVVOR MYHJR|UxRTBwMEWg{txO NGTsTmIzPjF|Nk[4OC=>
T84 NGf2NnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEDy[WkxNjVizszN Mn;IO|IhcA>? NE\1[pNFVVOR NVTvU25DUUN3ME2wMlA6KM7:TR?= NFHGcoMzPjF|Nk[4OC=>
LS180 MnLWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjkS5kxNjVizszN NVGxS5FFPzJiaB?= M{DGc2ROW09? NV\sZY1QUUN3ME2xJO69VQ>? MoK5NlYyOzZ4OES=
SW948 NWf1To9oT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYXnOItWOC53IN88US=> MlzSO|IhcA>? NGX4XYxFVVOR NFXhfWZKSzVyPUGg{txO MWeyOlE{PjZ6NB?=
HCT15 MlXFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoXCNE42KM7:TR?= NYHhTlVPPzJiaB?= MYLEUXNQ NV;lUJR5UUN3MEywMlQh|ryP NIXl[5QzPjF|Nk[4OC=>
DLD-1 NELx[mZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPSNE42KM7:TR?= MnTQO|IhcA>? NH;JVJFFVVOR NXG0fYhxUUN3MEywMlgh|ryP NHvvS3kzPjF|Nk[4OC=>
MIP-101 M{fYeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorsNE42KM7:TR?= MonxO|IhcA>? MUTEUXNQ NEizSFNKSzVyPUGg{txO Ml3GNlYyOzZ4OES=
SNU1544 MkXuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEnQdIQxNjVizszN NYLBbWszPzJiaB?= Mmn6SG1UVw>? NFf2b2hKSzVyPUGg{txO NXW5Xpk2OjZzM{[2PFQ>
OCI-Ly10 M3TTSWN6fG:2b4jpZ{BCe3OjeR?= NGT1WmU4OiCq NF\kUGlFVVOR MoTMTWM2OD1yLkC1PEDPxE1? M4[y[VI2QDd6M{Ox
SU-DHL2 MkDtR5l1d3SxeHnjJGF{e2G7 NHjOZ4I4OiCq Ml[4SG1UVw>? M{jGN2lEPTB;MD6wNUDPxE1? M3XDb|I2QDd6M{Ox
OCI-LY7 MY\DfZRwfG:6aXOgRZN{[Xl? MV[3NkBp MXPEUXNQ NF;DeHBKSzVyPUCuNFgyKM7:TR?= MV:yOVg4QDN|MR?=
SU-DHL6 NETXNnREgXSxdH;4bYMhSXO|YYm= M1LNRlczKGh? NX\wXGtyTE2VTx?= M2[2TmlEPTB;MD60PFIh|ryP NYXofJhDOjV6N{izN|E>
Jeko-1 M1jUT2N6fG:2b4jpZ{BCe3OjeR?= M4PuelczKGh? NYjqUFVQTE2VTx?= NGfsfY5KSzVyPUCuNFI6KM7:TR?= MmfGNlU5Pzh|M{G=
JVM-2 MULDfZRwfG:6aXOgRZN{[Xl? NX\Pc2ZLPzJiaB?= NVTyU5BiTE2VTx?= MX3JR|UxRTBwMEGg{txO NHW2SW4zPTh5OEOzNS=>
Rec-1 MW\DfZRwfG:6aXOgRZN{[Xl? M3nxV|czKGh? MVfEUXNQ M{S2d2lEPTB;MD6wPFch|ryP NX7F[oNoOjV6N{izN|E>
Z-138 NVvX[VlKS3m2b4TvfIlkKEG|c3H5 NEDT[GU4OiCq MVjEUXNQ MnvnTWM2OD1yLkCxN{DPxE1? MlvaNlU5Pzh|M{G=
H9 NGP2bmJEgXSxdH;4bYMhSXO|YYm= MonyO|IhcA>? M4j4SmROW09? M3nPZWlEPTB;MD62JO69VQ>? NEL4fYwzPTh5OEOzNS=>
HH MnnJR5l1d3SxeHnjJGF{e2G7 NX72cI1qPzJiaB?= M3HIWmROW09? NIrPe3lKSzVyPUCuO{DPxE1? MWiyOVg4QDN|MR?=
DND41 MnPBR5l1d3SxeHnjJGF{e2G7 MXu3NkBp MnXxSG1UVw>? MojwTWM2OD1yLkGg{txO NHnvd4MzPTh5OEOzNS=>
CCL119 NVWydWxQS3m2b4TvfIlkKEG|c3H5 NHHSUnE4OiCq NVzXR3lHTE2VTx?= Mki3TWM2OD1yLkC2NkDPxE1? Ml33NlU5Pzh|M{G=
J.Cam 1.6 NXPDZWU5S3m2b4TvfIlkKEG|c3H5 NUfRO5FHPzJiaB?= MXjEUXNQ NHnWTZRKSzVyPUCuNVA2KM7:TR?= NVf3W5hEOjV6N{izN|E>
Sup-T1 M1zMUmN6fG:2b4jpZ{BCe3OjeR?= NXnGZVRzPzJiaB?= MkfDSG1UVw>? M{HNXGlEPTB;Mj6xOFIh|ryP MnfUNlU5Pzh|M{G=
Tib 152 MWPDfZRwfG:6aXOgRZN{[Xl? M1\6N|czKGh? NFXjVXpFVVOR NXLES3g6UUN3ME2wMlgh|ryP M{TuNFI2QDd6M{Ox
MCF7 MkjySpVv[3Srb36gRZN{[Xl? NVvaVJVbPSEQvF2= MWOyOEBp Mo\wSG1UVw>? MkLGTY5lfWOnczDHNk9OKGG{cnXzeC=> NEK2OYMzPTh|NESwNS=>
MDA-MB-231 NHzqTYVHfW6ldHnvckBCe3OjeR?= Mn35OUDPxE1? MUOyOEBp NWiyT5pCTE2VTx?= NYG1XmZ[UW6mdXPld{BIOy:PIHHydoV{fA>? Ml\2NlU5OzR2MEG=
MCF7 MnnCSpVv[3Srb36gRZN{[Xl? M2nUXlUh|ryP MXuyOEBp NIDRW2FFVVOR MX3E[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNU9ETEN{ MlvVNlU5OzR2MEG=
MCF7 M1P0U2Z2dmO2aX;uJGF{e2G7 NX3uTWlMPSEQvF2= NUC4bGNpOjRiaB?= Moq1SG1UVw>? NYTxcHNITGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzJ? MYOyOVg{PDRyMR?=
MCF7 MXPGeY5kfGmxbjDBd5NigQ>? MmPnOUDPxE1? MUGyOEBp MV3EUXNQ NIXteohF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gZ5lkdGmwIFKx M3vpZlI2QDN2NECx
MCF7 NUK5VngxTnWwY4Tpc44hSXO|YYm= MnTDOUDPxE1? MXSyOEBp NF7zSJpFVVOR Ml73TY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> NF\sNHUzPTh|NESwNS=>
MCF7 M1zHbmZ2dmO2aX;uJGF{e2G7 NIDQfW82KM7:TR?= MY[yOEBp Ml\qSG1UVw>? MUTJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF? MYCyOVg{PDRyMR?=
MDA-MB-231 MXLGeY5kfGmxbjDBd5NigQ>? MXK1JO69VQ>? NWX5O3lTOjRiaB?= MWDEUXNQ NVn4cW5LTGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=> M{TiflI2QDN2NECx
MDA-MB-231 NXLlTnF5TnWwY4Tpc44hSXO|YYm= M3G2VFEh|ryP MljaNlQhcA>? MYXEUXNQ MVrJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNi=> MlvqNlU5OzR2MEG=
MDA-MB-231 M3jCO2Z2dmO2aX;uJGF{e2G7 MUe1JO69VQ>? M1L5RlI1KGh? Ml7WSG1UVw>? M1fCWWRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG= MUSyOVg{PDRyMR?=
MDA-MB-231 NInCZpBHfW6ldHnvckBCe3OjeR?= NUPVUJNyPSEQvF2= NGnONYwzPCCq MkjzSG1UVw>? NYTUeGdHUW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJJAzOSCZYX[xM2NqeDF? NHq1eY0zPTh|NESwNS=>
MDA-MB-231 MnPxSpVv[3Srb36gRZN{[Xl? MnPsOUDPxE1? MV:yOEBp NHHWcIlFVVOR NUjDOmhtUW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJJAzPyCNaYCx MXmyOVg{PDRyMR?=
MDA-MB-231 NFiwfGZHfW6ldHnvckBCe3OjeR?= NXvkdmJnPSEQvF2= NFPYWWEzPCCq MkPPSG1UVw>? MojyTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIIC1Ny=> MVuyOVg{PDRyMR?=
MCF7 MkOwRZBweHSxc3nzJGF{e2G7 Mn7tOUDPxE1? M2PZWVI1KGh? NGXadVRFVVOR MlTJTY5lfWOnczDhdI9xfG:2aXOg[IVifGh? MnzxNlU5OzR2MEG=
MDA-MB-231 MoT5RZBweHSxc3nzJGF{e2G7 MUC1JO69VQ>? MX:yOEBp MVvEUXNQ MXnJcoR2[2W|IHHwc5B1d3SrYzDk[YF1cA>? MYGyOVg{PDRyMR?=
MCF7 M{eyOmZ2dmO2aX;uJGF{e2G7 NUf0[5RCOSEQvF2= NEPHZVA4OiCq NXXmN4NPTE2VTx?= Ml\qTY5lfWOnczDheZRweGijZ3njJIRm[XSq M3rOZ|I2QDN2NECx
MDA-MB-231 NIrVeIVHfW6ldHnvckBCe3OjeR?= MYKxJO69VQ>? MmPJO|IhcA>? MlnhSG1UVw>? M3viPWlv\HWlZYOgZZV1d3CqYXfpZ{Bl\WG2aB?= M1HPe|I2QDN2NECx
U-2 OS NWTw[2RGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGnpUWI2OCEQvF2= M2jWNlI1KGh? NICycZlFVVOR NHTmbFRKSzVyPUG2MlYh|ryP NXu1UpB7OjV5OUK4NVE>
MG-63 MlvNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUm1NEDPxE1? MWqyOEBp MnmzSG1UVw>? MlXNTWM2OD17LkWg{txO M17yW|I2Pzl{OEGx
U-2 OS Mmq5RZBweHSxc3nzJGF{e2G7 M{PN[|Uh|ryP NET4T3UzPCCq NVnTXWpJTE2VTx?= MX;JcoR2[2W|IHHwc5B1d3SrYzDj[YxtKGSnYYTo NHfsNGIzPTd7MkixNS=>
MG-63 MkTBRZBweHSxc3nzJGF{e2G7 Mn7DOUDPxE1? MYWyOEBp MUPEUXNQ Mn7rTY5lfWOnczDhdI9xfG:2aXOgZ4VtdCCmZXH0bC=> MoLPNlU4QTJ6MUG=
U-2 OS NGTXfpZHfW6ldHnvckBCe3OjeR?= MmX2OUDPxE1? M1\ieFI1KGh? MV;EUXNQ MUDQdo9ud3SnczDheZRweGijZ3njJINmdGxiZHXheIg> NHjZTo8zPTd7MkixNS=>
MG-63 MVrGeY5kfGmxbjDBd5NigQ>? MmjoOUDPxE1? NV\0eIczOjRiaB?= NV6zV5Q2TE2VTx?= M1rPN3Bzd22xdHXzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? MXyyOVc6OjhzMR?=
PANC-1 MmXSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHLYZYE2OCEQvF2= NGfmSWIzPCCq NYTpbI06TE2VTx?= M2DTfmlEPTB;Nz6xJO69VQ>? NHzyV|EzPTZ|MkKyOS=>
BxPC-3 NXm2ZWt1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV:1NEDPxE1? M3vNRVI1KGh? MWHEUXNQ M2XRc2lEPTB;Nj64JO69VQ>? NVe1NXZOOjV4M{KyNlU>
PANC-1 NGLuZmRHfW6ldHnvckBCe3OjeR?= NYrRe|M4PSEQvF2= M3nrblI1KGh? MmHWSG1UVw>? NFXKb5FKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V? NW\YN|BvOjV4M{KyNlU>
BxPC-3 MlHzSpVv[3Srb36gRZN{[Xl? Mof6OUDPxE1? NYPlN3hEOjRiaB?= Mom3SG1UVw>? MmXDTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dDDpckBIOi:PIIDoZZNm M4P1VVI2PjN{MkK1
PANC-1 M4roZ2Z2dmO2aX;uJGF{e2G7 NU\oR5k{PSEQvF2= NGXEbXQzPCCq NWL3So1wTE2VTx?= NE\PenBKdmS3Y3XzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? MnPPNlU3OzJ{MkW=
BxPC-3 NV;5d2JZTnWwY4Tpc44hSXO|YYm= NXjuPYw2PSEQvF2= M3rJOFI1KGh? NWnNS|lETE2VTx?= M3vz[2lv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp Ml3NNlU3OzJ{MkW=
SKOV3 MkOzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWexNFAh|ryP NFnsPGozPCCq NEXPXpRFVVOR M2LKUGlEPTB;MkCuOFgh|ryP M3PxNVI2PjJ2N{Ww
OVCAR4 NGLseJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2TqUVExOCEQvF2= NXfFUZQzOjRiaB?= NYfIWGZzTE2VTx?= NEnOd5RKSzVyPUKyMlE{KM7:TR?= NXvCRmJROjV4MkS3OVA>
SKOV3 MlHBSpVv[3Srb36gRZN{[Xl? MVG1JO69VQ>? M3LvWlczKGh? MUHEUXNQ NHLWcVBKdmS3Y3XzJGczN01iYYLy[ZN1 MWiyOVYzPDd3MB?=
OVCAR4 Mn[5SpVv[3Srb36gRZN{[Xl? MVG1JO69VQ>? MnjLO|IhcA>? M4H1NWROW09? Mo\XTY5lfWOnczDHNk9OKGG{cnXzeC=> NFzFPZAzPTZ{NEe1NC=>
SKOV3 M3LJeGFxd3C2b4Ppd{BCe3OjeR?= NWDZOnd2PSEQvF2= M4TWc|I1KGh? MYfEUXNQ MVzJcoR2[2W|IHHwc5B1d3Orcx?= MYKyOVYzPDd3MB?=
OVCAR4 MYDBdI9xfG:|aYOgRZN{[Xl? NIrW[Zg2KM7:TR?= MkPQNlQhcA>? NY\adlNJTE2VTx?= MVPJcoR2[2W|IHHwc5B1d3Orcx?= NWPwXpRTOjV4MkS3OVA>
AGS NXLhbGplT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3j2VFI2KM7:TR?= M2LBSVI1KGh? NH:zd4pFVVOR MVjJR|UxRTF7LkC5JO69VQ>? NEfvOIMzPTZyOUmyNy=>
NCI-N78 NUjVd41TT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4GySlI2KM7:TR?= NHLHflgzPCCq MXfEUXNQ NUnaOHh[UUN3ME2yOk4{OyEQvF2= NInVOmwzPTZyOUmyNy=>
AGS NFnLPFhCeG:ydH;zbZMhSXO|YYm= NVTUXlRRPSEQvF2= M{nlWFI1KGh? M3nuVmROW09? NIS3OI5KdmS3Y3XzJIFxd3C2b4Ppdy=> Mm[1NlU3ODl7MkO=
NCI-N78 NYTHclg4SXCxcITvd4l{KEG|c3H5 MnL0OUDPxE1? MlrwNlQhcA>? MXXEUXNQ NHjtVZhKdmS3Y3XzJIFxd3C2b4Ppdy=> NF;VNoUzPTZyOUmyNy=>
AGS MUjGeY5kfGmxbjDBd5NigQ>? MnTqOUDPxE1? NWnRVIhTOjRiaB?= M32zbWROW09? NXLK[4J{UW6mdXPld{B1cGViYYX0c5Bp[We7 NVnsZWlSOjV4MEm5NlM>
NCI-N78 NEHze5BHfW6ldHnvckBCe3OjeR?= M2XU[FUh|ryP NVrsWXJWOjRiaB?= NWXVSWE{TE2VTx?= MXrJcoR2[2W|IITo[UBifXSxcHjh[5k> MVGyOVYxQTl{Mx?=
HSC-3 NY\rPW9yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfKSZcyKM7:TR?= MonBOFghcA>? M1r1SGlEPTB;MD61OEDPxE1? NFvvTWIzPTN4NkG0Ny=>
GB30 Mn\iS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\BNUDPxE1? MYC3JIQ> NYPsN5hZTE2VTx?= MmrDTWM2OD1yLkCxNUDPxE1? MlPsNlUyODZ2Mki=
GB9 NHjzbJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXyxJO69VQ>? MVO3JIQ> NFPGUYVFVVOR NILRUVlKSzVyPUCuNFI1KM7:TR?= M4r5N|I2OTB4NEK4
GB169 Mn;2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYWxJO69VQ>? MWq3JIQ> MojGSG1UVw>? NF\ES3VKSzVyPUCuNFMzKM7:TR?= MWOyOVExPjR{OB?=
T24 NV;ZZmRXTnWwY4Tpc44hSXO|YYm= MWmxJO69VQ>? NHOxVlk1QCCq NHv3VI9FVVOR NVXsOHVtUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> NYXKc5l6OjN2MEO2N|M>
RT4 MUTGeY5kfGmxbjDBd5NigQ>? MmD0NUDPxE1? M4\He|Q5KGh? MW\EUXNQ NFTZSo5KdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0 MoHNNlM1ODN4M{O=
UM-UC-3 NHzWbWhHfW6ldHnvckBCe3OjeR?= NW[4[2NUOSEQvF2= NHHlPZc1QCCq NUTtWGlGTE2VTx?= M3y0dGlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= M1T6ZVI{PDB|NkOz
T24 M4S0T2Fxd3C2b4Ppd{BCe3OjeR?= NUn6ZpRDOy5zNjFOwG0> M1TSNlk3KGh? MlzaSG1UVw>? NXPweIZGUUN3ME2wMlA{ODZizszN NFjjXoYzOzRyM{[zNy=>
RT4 NHTTdo1CeG:ydH;zbZMhSXO|YYm= NHjFflg{NjF4IN88US=> MYK5OkBp NULBT3lrTE2VTx?= MWHJR|UxRTBwMUG5PEDPxE1? MmG0NlM1ODN4M{O=
UM-UC-3 M1;zSWFxd3C2b4Ppd{BCe3OjeR?= NWewNWFbOy5zNjFOwG0> NUT2RoJoQTZiaB?= Ml3HSG1UVw>? MUXJR|UxRTBwMES0PUDPxE1? M1zGZVI{PDB|NkOz
OVCAR-5 M{T3cWZ2dmO2aX;uJGF{e2G7 NHnEbXQ2OCCwTR?= MlTqTY5pcWKrdIOgZ4VtdCCvaXfyZZRqd25? M1T3elI{OzN2M{K3
SKOV3ip2 NWjBVG5ZTnWwY4Tpc44hSXO|YYm= NXjK[pNbPTBibl2= Mnq4TY5pcWKrdIOgZ4VtdCCvaXfyZZRqd25? NFO5fYEzOzN|NEOyOy=>
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COG-LL-317 M{PhWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFjtVHEyOCEQvF2= NWnGNI5pQTZiaB?= NXrPe3ViUUN3ME2wMlA1PyEQvF2= NFLDTWozODFyOEOzPC=>
RS4-11 NYjFWHJmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUOxNEDPxE1? NXS2[XhLQTZiaB?= NEi5blVKSzVyPUCuNFE5KM7:TR?= NYjGUZZPOjBzMEizN|g>
MOLT-4 M1TJXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojJNVAh|ryP NWe0NFVnQTZiaB?= M1:5PWlEPTB;MD6wNlYh|ryP NV3CXoFMOjBzMEizN|g>
CCRF-CEM M4GxfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFq3UpQyOCEQvF2= NXr3SFZDQTZiaB?= MWXJR|UxRTBwMEm0JO69VQ>? NGj1em0zODFyOEOzPC=>
Kasumi-1 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;RcYEyOCEQvF2= NFmxT3E6PiCq MVjJR|UxRTBwMUCzJO69VQ>? NYjnZnlPOjBzMEizN|g>
Karpas-299 M3vQcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX3KZVlXOTBizszN Ml3HPVYhcA>? NULlXmI3UUN3ME2wMlA{QCEQvF2= NGmzfo4zODFyOEOzPC=>
Ramos-RA1 NIXSdG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrLT2J1OTBizszN NITFPJE6PiCq M1zTRWlEPTB;MD6xNlch|ryP NH7sWHYzODFyOEOzPC=>

... 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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