Alisertib (MLN8237)

目录号：S1133

Alisertib (MLN8237) Chemical Structure

Molecular Weight(MW): 518.92

Alisertib (MLN8237)是一种选择性Aurora A抑制剂，无细胞试验中IC50为1.2 nM，作用于Aurora A比作用于Aurora B选择性强200倍以上。Phase 3。

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产品安全说明书

Aurora Kinase抑制剂选择性比较

生物活性

产品描述 Alisertib (MLN8237)是一种选择性Aurora A抑制剂，无细胞试验中IC50为1.2 nM，作用于Aurora A比作用于Aurora B选择性强200倍以上。Phase 3。
特性 MLN8237 是第一个口服有效的小分子Aurora A激酶选择性抑制剂。
靶点
Aurora A [1]
(Cell-free assay)
1.2 nM
体外研究

MLN8237作用于Aurora A选择性比作用于结构相关的Aurora B 高200多倍，IC50为396.5 nM, 而对205种其他激酶则没有显著活性。[1] 0.5 μM MLN8237处理MM1.S和 OPM1 细胞，抑制 Aurora A磷酸化，而不影响 Aurora B调节的组蛋白H3磷酸化。MLN8237作用于多发性骨髓瘤(MM) 细胞系，显著抑制细胞增殖，IC50为0.003-1.71 μM。在BM 基质细胞，IL-6和 IGF-1 存在时，MLN8237作用于原代MM 细胞和MM细胞系，抗增殖活性比只有MLN8237单独作用时高很多。0.5 μM MLN8237 作用于原代MM细胞和细胞系，使G2/M 期细胞提高2到6倍，且显著诱导凋亡和衰老，涉及p53, p21 和p27的上调,及 PARP,caspase 3,和 caspase 9的裂解。此外, MLN8237和 Dexamethasone联用具有协同作用，具有强抗MM 功效, 而和Doxorubicin 及Bortezomib联用则具有另外的功能。[2] 0.5 μM MLN8237处理 FLO-1, OE19, 和OE33 食管腺癌细胞系，抑制集落形成，且显著提高多倍体细胞百分数,随后提高G1期细胞百分数,而与 Cisplatin (2.5 μM)联用则效果进一步提高，与单独用药相比，诱导产生更多, TAp73β, PUMA, NOXA, cleaved caspase-3, 和cleaved PARP。[3]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGXydnkxNjVizszN NITzW|Y4OiCq M1vlPWROW09? Mn;RTWM2OD1yLkC0JO69VQ>? NUTHdWVLOjZzM{[2PFQ>
LS174T MlvQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NInCWJYxNjVizszN MVW3NkBp MlLUSG1UVw>? NV\pOYFTUUN3ME2wMlA2KM7:TR?= M3XHT|I3OTN4Nki0
T84 NETIZXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYnHdY9xOC53IN88US=> MV23NkBp NIPSTpRFVVOR NHjsT|lKSzVyPUCuNFkh|ryP NUnOdHh6OjZzM{[2PFQ>
LS180 M2TkWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGr5VYUxNjVizszN NFvzS4c4OiCq NVT6SGdlTE2VTx?= NWe5Z2h[UUN3ME2xJO69VQ>? NHHCbmIzPjF|Nk[4OC=>
SW948 NIP3fXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWCwMlUh|ryP NXexcWh7PzJiaB?= NH;O[YRFVVOR NH3FR3lKSzVyPUGg{txO NH:4R2IzPjF|Nk[4OC=>
HCT15 M{ju[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV2wMlUh|ryP MnP3O|IhcA>? NYrxT5BuTE2VTx?= NUXiOnFsUUN3MEywMlQh|ryP NVnLSVZ3OjZzM{[2PFQ>
DLD-1 MkjQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFPHXI4xNjVizszN M2fSOFczKGh? M2PJbGROW09? MlvUTWM2ODxyLkig{txO NF36WmUzPjF|Nk[4OC=>
MIP-101 NX70dYJoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2rhcFAvPSEQvF2= MUC3NkBp M3jnR2ROW09? MnjaTWM2OD1zIN88US=> NHPtZo8zPjF|Nk[4OC=>
SNU1544 NF;mO2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1jibFAvPSEQvF2= MXW3NkBp NX;MZ3Y5TE2VTx?= MnjrTWM2OD1zIN88US=> MYSyOlE{PjZ6NB?=
OCI-Ly10 MXzDfZRwfG:6aXOgRZN{[Xl? MlP2O|IhcA>? MmTWSG1UVw>? NYryRnFUUUN3ME2wMlA2QCEQvF2= NGfVV3QzPTh5OEOzNS=>
SU-DHL2 M1vuOWN6fG:2b4jpZ{BCe3OjeR?= M1viVVczKGh? M{i1WGROW09? M4XrZ2lEPTB;MD6wNUDPxE1? MYiyOVg4QDN|MR?=
OCI-LY7 MofGR5l1d3SxeHnjJGF{e2G7 NIm3WpY4OiCq MVnEUXNQ NG[0PXRKSzVyPUCuNFgyKM7:TR?= M{SxeVI2QDd6M{Ox
SU-DHL6 NWDOb|NXS3m2b4TvfIlkKEG|c3H5 M1r5flczKGh? MVfEUXNQ NHzrVXFKSzVyPUCuOFgzKM7:TR?= MoPDNlU5Pzh|M{G=
Jeko-1 M1vNV2N6fG:2b4jpZ{BCe3OjeR?= M3z5dVczKGh? MYPEUXNQ NGrFNnVKSzVyPUCuNFI6KM7:TR?= NI\2dI0zPTh5OEOzNS=>
JVM-2 NV3DNnpPS3m2b4TvfIlkKEG|c3H5 NHTGSIg4OiCq MmnTSG1UVw>? NXjPOGRZUUN3ME2wMlAyKM7:TR?= NFK2XWEzPTh5OEOzNS=>
Rec-1 MXTDfZRwfG:6aXOgRZN{[Xl? MX63NkBp NWPSXlByTE2VTx?= M2qzemlEPTB;MD6wPFch|ryP NY\FcG46OjV6N{izN|E>
Z-138 M4D5PGN6fG:2b4jpZ{BCe3OjeR?= NUjJcoNpPzJiaB?= NFTVcXlFVVOR NH73e4NKSzVyPUCuNFE{KM7:TR?= MWSyOVg4QDN|MR?=
H9 NHPHfIpEgXSxdH;4bYMhSXO|YYm= MkXTO|IhcA>? M1r6fGROW09? NFu2[41KSzVyPUCuOkDPxE1? MVKyOVg4QDN|MR?=
HH MnTpR5l1d3SxeHnjJGF{e2G7 MoTFO|IhcA>? NHfFTIZFVVOR MWPJR|UxRTBwNzFOwG0> M{TMe|I2QDd6M{Ox
DND41 NXfSb4RMS3m2b4TvfIlkKEG|c3H5 NXPXcoVGPzJiaB?= NUXMd2tQTE2VTx?= MUfJR|UxRTBwMTFOwG0> M2i4RVI2QDd6M{Ox
CCL119 NUPVcW9GS3m2b4TvfIlkKEG|c3H5 M4T6XFczKGh? NFzaeVJFVVOR MkfxTWM2OD1yLkC2NkDPxE1? NH[zNpAzPTh5OEOzNS=>
J.Cam 1.6 NGrhclhEgXSxdH;4bYMhSXO|YYm= NEf6R244OiCq MmKzSG1UVw>? NYXRNYVqUUN3ME2wMlExPSEQvF2= MoO1NlU5Pzh|M{G=
Sup-T1 M3HHbGN6fG:2b4jpZ{BCe3OjeR?= M3fDelczKGh? M3X1ZmROW09? M2LwcGlEPTB;Mj6xOFIh|ryP MXiyOVg4QDN|MR?=
Tib 152 NYrJelROS3m2b4TvfIlkKEG|c3H5 NHvGU4E4OiCq NHLhfmtFVVOR NF;C[49KSzVyPUCuPEDPxE1? NXfOdpRsOjV6N{izN|E>
MCF7 NIWyNWtHfW6ldHnvckBCe3OjeR?= MYC1JO69VQ>? Mn7hNlQhcA>? M1KwdmROW09? MXHJcoR2[2W|IFeyM20h[XK{ZYP0 MnjVNlU5OzR2MEG=
MDA-MB-231 NITEVXRHfW6ldHnvckBCe3OjeR?= NFe4NVA2KM7:TR?= Ml35NlQhcA>? MYXEUXNQ MYjJcoR2[2W|IFezM20h[XK{ZYP0 MVSyOVg{PDRyMR?=
MCF7 NHKzOpBHfW6ldHnvckBCe3OjeR?= Mkj3OUDPxE1? MmXVNlQhcA>? NF7HRmVFVVOR MYLE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNU9ETEN{ MmnSNlU5OzR2MEG=
MCF7 MoTBSpVv[3Srb36gRZN{[Xl? MXy1JO69VQ>? MnLENlQhcA>? NVK0TVVUTE2VTx?= MUDE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNi=> M2WzRlI2QDN2NECx
MCF7 NX;ISIk4TnWwY4Tpc44hSXO|YYm= MoDyOUDPxE1? M1z0NVI1KGh? MlLzSG1UVw>? Mo\CSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIHP5Z4xqdiCEMR?= MmXtNlU5OzR2MEG=
MCF7 MUHGeY5kfGmxbjDBd5NigQ>? NF7zWnU2KM7:TR?= MWWyOEBp NYHU[WJvTE2VTx?= NIG4XpBKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFIyKFejZkGvR4lxOQ>? MorvNlU5OzR2MEG=
MCF7 MWXGeY5kfGmxbjDBd5NigQ>? MWW1JO69VQ>? NIjH[5gzPCCq NEn2RXRFVVOR NFnkd5RKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFI4KEurcEG= NVHUSXZ[OjV6M{S0NFE>
MDA-MB-231 NGW3b4RHfW6ldHnvckBCe3OjeR?= MWG1JO69VQ>? NI\nTlgzPCCq MmT6SG1UVw>? MX7E[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNU9ETEN{ MYKyOVg{PDRyMR?=
MDA-MB-231 MWXGeY5kfGmxbjDBd5NigQ>? NWi0UJpEOSEQvF2= M3y1XVI1KGh? NWe4XHNVTE2VTx?= M{mxVmlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz MYmyOVg{PDRyMR?=
MDA-MB-231 M1TlXmZ2dmO2aX;uJGF{e2G7 MlK2OUDPxE1? NH\nNYQzPCCq NHXXSpFFVVOR MYfE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiY4njcIlvKEJz MmPjNlU5OzR2MEG=
MDA-MB-231 MUPGeY5kfGmxbjDBd5NigQ>? MXi1JO69VQ>? MoC4NlQhcA>? NXj4fXFmTE2VTx?= MmrXTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> MnLUNlU5OzR2MEG=
MDA-MB-231 MWrGeY5kfGmxbjDBd5NigQ>? M1PnRVUh|ryP Ml64NlQhcA>? NWe0V2FyTE2VTx?= Ml3yTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyO{BMcXBz M1PYOFI2QDN2NECx
MDA-MB-231 MkHtSpVv[3Srb36gRZN{[Xl? NXL6WnE3PSEQvF2= NV7Ce4NoOjRiaB?= MXXEUXNQ NX7EeYRMUW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJJA2Ow>? MnLBNlU5OzR2MEG=
MCF7 Mlr6RZBweHSxc3nzJGF{e2G7 NFOxS2M2KM7:TR?= NX7rbmJMOjRiaB?= NGDa[npFVVOR M{LPTWlv\HWlZYOgZZBweHSxdHnjJIRm[XSq NGnFTnEzPTh|NESwNS=>
MDA-MB-231 MlHHRZBweHSxc3nzJGF{e2G7 M4XzWVUh|ryP M36welI1KGh? M13iXmROW09? MlPkTY5lfWOnczDhdI9xfG:2aXOg[IVifGh? NVLTVnpUOjV6M{S0NFE>
MCF7 M2jIfWZ2dmO2aX;uJGF{e2G7 M4TVN|Eh|ryP NXO4cGtCPzJiaB?= M1voUWROW09? MXrJcoR2[2W|IHH1eI9xcGGpaXOg[IVifGh? NHfLRmYzPTh|NESwNS=>
MDA-MB-231 MVzGeY5kfGmxbjDBd5NigQ>? MlfZNUDPxE1? MVi3NkBp M3XR[WROW09? NVW2WWZiUW6mdXPld{BifXSxcHjh[4lkKGSnYYTo MUKyOVg{PDRyMR?=
U-2 OS NXPMV2c5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVfvWppqPTBizszN NHnnZm8zPCCq NYDVcHNOTE2VTx?= NXzrTHI1UUN3ME2xOk43KM7:TR?= MVmyOVc6OjhzMR?=
MG-63 MofLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXjIe|F5PTBizszN MXGyOEBp NYXEZ2pUTE2VTx?= MmXYTWM2OD17LkWg{txO MoXRNlU4QTJ6MUG=
U-2 OS M1:5UWFxd3C2b4Ppd{BCe3OjeR?= MnLEOUDPxE1? MWCyOEBp NV7KZ3cxTE2VTx?= NIP6T4VKdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRp NVXTOm92OjV5OUK4NVE>
MG-63 NYrmTmI2SXCxcITvd4l{KEG|c3H5 Mn;FOUDPxE1? M1rOOFI1KGh? NVrZc2lUTE2VTx?= M1PscWlv\HWlZYOgZZBweHSxdHnjJINmdGxiZHXheIg> M3;hfFI2Pzl{OEGx
U-2 OS NGPYWWJHfW6ldHnvckBCe3OjeR?= NVfzVllVPSEQvF2= MVeyOEBp MnzkSG1UVw>? MkW3VJJwdW:2ZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp M3PYdlI2Pzl{OEGx
MG-63 MYnGeY5kfGmxbjDBd5NigQ>? M2e0dVUh|ryP MoLwNlQhcA>? MUXEUXNQ MoXpVJJwdW:2ZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp NF\PO3ozPTd7MkixNS=>
PANC-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonVOVAh|ryP NIW1c4EzPCCq MknPSG1UVw>? NUXufoxpUUN3ME23MlEh|ryP MYWyOVY{OjJ{NR?=
BxPC-3 Ml3TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTRUGc2OCEQvF2= MmTRNlQhcA>? NYHoXW12TE2VTx?= NWnU[o9pUUN3ME22Mlgh|ryP NVvpc2x{OjV4M{KyNlU>
PANC-1 NHzCVY9HfW6ldHnvckBCe3OjeR?= NFXsUnU2KM7:TR?= MUKyOEBp MnTBSG1UVw>? MofuTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dDDpckBIOi:PIIDoZZNm M3\zblI2PjN{MkK1
BxPC-3 NX35UmQ3TnWwY4Tpc44hSXO|YYm= MUS1JO69VQ>? M3;jN|I1KGh? MVTEUXNQ MoSxTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dDDpckBIOi:PIIDoZZNm M{m1NFI2PjN{MkK1
PANC-1 NHXYV|VHfW6ldHnvckBCe3OjeR?= MmDGOUDPxE1? MkTVNlQhcA>? Moj5SG1UVw>? MXPJcoR2[2W|IHH1eI9xcGGpaXOgZ4VtdCCmZXH0bC=> MnX1NlU3OzJ{MkW=
BxPC-3 MkTvSpVv[3Srb36gRZN{[Xl? MX[1JO69VQ>? NUnUXXRbOjRiaB?= NFTGSmpFVVOR MX7JcoR2[2W|IHH1eI9xcGGpaXOgZ4VtdCCmZXH0bC=> MUSyOVY{OjJ{NR?=
SKOV3 M4iyT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnvHNVAxKM7:TR?= NHXTdoIzPCCq NX;kW406TE2VTx?= MkPzTWM2OD1{MD60PEDPxE1? NVjrTZdiOjV4MkS3OVA>
OVCAR4 M{fwZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlX3NVAxKM7:TR?= MmPHNlQhcA>? NVzFXow{TE2VTx?= M2O3[mlEPTB;MkKuNVMh|ryP M3;MR|I2PjJ2N{Ww
SKOV3 M1nWRWZ2dmO2aX;uJGF{e2G7 MkTYOUDPxE1? NF;pNoQ4OiCq NGnKZppFVVOR MkHnTY5lfWOnczDHNk9OKGG{cnXzeC=> NEXidYozPTZ{NEe1NC=>
OVCAR4 NHXNfm1HfW6ldHnvckBCe3OjeR?= NXvXV|JKPSEQvF2= MUC3NkBp NUnSeWtRTE2VTx?= M1TIRmlv\HWlZYOgS|IwVSCjcoLld5Q> MlrCNlU3OjR5NUC=
SKOV3 Moq1RZBweHSxc3nzJGF{e2G7 NVHp[FRPPSEQvF2= MXOyOEBp MmrNSG1UVw>? MnOwTY5lfWOnczDhdI9xfG:|aYO= MmS3NlU3OjR5NUC=
OVCAR4 M4XDRmFxd3C2b4Ppd{BCe3OjeR?= MUW1JO69VQ>? M3r3b|I1KGh? NVPkdI17TE2VTx?= MnjwTY5lfWOnczDhdI9xfG:|aYO= MXOyOVYzPDd3MB?=
AGS MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVOyOUDPxE1? MX:yOEBp MoXCSG1UVw>? NVLU[|dLUUN3ME2xPU4xQSEQvF2= MYCyOVYxQTl{Mx?=
NCI-N78 NYL2dItKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;tO3IzPSEQvF2= M4XvZlI1KGh? NUjIc2xqTE2VTx?= MlLxTWM2OD1{Nj6zN{DPxE1? M37TVFI2PjB7OUKz
AGS MUjBdI9xfG:|aYOgRZN{[Xl? NUPyeZI{PSEQvF2= NVj4cYNsOjRiaB?= NV\HdHpFTE2VTx?= M2\iOWlv\HWlZYOgZZBweHSxc3nz NHjpdWczPTZyOUmyNy=>
NCI-N78 MlvFRZBweHSxc3nzJGF{e2G7 M4fwSFUh|ryP MoXpNlQhcA>? MX\EUXNQ MWHJcoR2[2W|IHHwc5B1d3Orcx?= NFvLOJAzPTZyOUmyNy=>
AGS MUfGeY5kfGmxbjDBd5NigQ>? MXW1JO69VQ>? M3jSNVI1KGh? MmDKSG1UVw>? NITHUXNKdmS3Y3XzJJRp\SCjdYTvdIhi\3l? M4DNdlI2PjB7OUKz
NCI-N78 M2C0PWZ2dmO2aX;uJGF{e2G7 MlPpOUDPxE1? MUKyOEBp MojTSG1UVw>? NWiw[VFiUW6mdXPld{B1cGViYYX0c5Bp[We7 NFfrdoszPTZyOUmyNy=>
HSC-3 Mk\sS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlW2NUDPxE1? NUjhOlRpPDhiaB?= MkHVTWM2OD1yLkW0JO69VQ>? NW\MNndvOjV|Nk[xOFM>
GB30 NWm5XVc6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV[xJO69VQ>? M3rFXVch\A>? NU\6d3d3TE2VTx?= M4Pue2lEPTB;MD6wNVEh|ryP NIDm[JEzPTFyNkSyPC=>
GB9 NV[3Vox2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7YZlYyKM7:TR?= MmfDO{Bl MVHEUXNQ MkDiTWM2OD1yLkCyOEDPxE1? Ml21NlUyODZ2Mki=
GB169 NWDzZZd4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkTvNUDPxE1? NVfJSplXPyCm MW\EUXNQ NI\B[nRKSzVyPUCuNFMzKM7:TR?= M2HseFI2OTB4NEK4
T24 NXG3OZd4TnWwY4Tpc44hSXO|YYm= NX;CfXhUOSEQvF2= M1fy[FQ5KGh? M33SWGROW09? MYjJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2 NVPmUJlmOjN2MEO2N|M>
RT4 NFPofppHfW6ldHnvckBCe3OjeR?= MnrHNUDPxE1? MUG0PEBp NIPRVnBFVVOR M3PM[Glv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= NYiyfldFOjN2MEO2N|M>
UM-UC-3 MmXWSpVv[3Srb36gRZN{[Xl? MUOxJO69VQ>? M2DGSlQ5KGh? M1noZWROW09? MljkTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= NYHFN5V[OjN2MEO2N|M>
T24 NF\0XHFCeG:ydH;zbZMhSXO|YYm= M1;neFMvOTZizszN NGfzUlg6PiCq MnvFSG1UVw>? NFfVdXhKSzVyPUCuNFMxPiEQvF2= MVeyN|QxOzZ|Mx?=
RT4 MYPBdI9xfG:|aYOgRZN{[Xl? Ml7lN{4yPiEQvF2= Mm\zPVYhcA>? MX3EUXNQ MUnJR|UxRTBwMUG5PEDPxE1? MlrVNlM1ODN4M{O=
UM-UC-3 M3\EdGFxd3C2b4Ppd{BCe3OjeR?= NYLXPVd7Oy5zNjFOwG0> MYW5OkBp MlLqSG1UVw>? M13N[mlEPTB;MD6wOFQ6KM7:TR?= MofUNlM1ODN4M{O=
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SJ-GBM2 Mn;vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLmd2FVOTBizszN MlnSPVYhcA>? NIPMZVZKSzVyPUCuNFUxKM7:TR?= M2DJeVIxOTB6M{O4
NALM-6 M2jvV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnnJNVAh|ryP MoLKPVYhcA>? M4r0RmlEPTB;MD6wOlIh|ryP M2\OV|IxOTB6M{O4
COG-LL-317 MlzpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnFfXpuOTBizszN NHjGTo06PiCq NYjOZ2ZGUUN3ME2wMlA1PyEQvF2= MnrYNlAyODh|M{i=
RS4-11 MlvNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{faRVExKM7:TR?= NEjZVYM6PiCq M2DoUWlEPTB;MD6wNVgh|ryP MVWyNFExQDN|OB?=
MOLT-4 NVPUTnpwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXPZoEyOCEQvF2= NYHxPJZRQTZiaB?= M3\NXGlEPTB;MD6wNlYh|ryP NVnZe4hmOjBzMEizN|g>
CCRF-CEM NF;0bYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;sZoYyOCEQvF2= M3nXOlk3KGh? M4nCRmlEPTB;MD6wPVQh|ryP M2O5Z|IxOTB6M{O4
Kasumi-1 MlH4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PqO|ExKM7:TR?= M3XtXFk3KGh? M{[2N2lEPTB;MD6xNFMh|ryP MVGyNFExQDN|OB?=
Karpas-299 M{X5Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLKeHAyOCEQvF2= NEPTUJA6PiCq NUexeGRTUUN3ME2wMlA{QCEQvF2= NH3lemIzODFyOEOzPC=>
Ramos-RA1 MmOyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIHXPVQyOCEQvF2= MVe5OkBp NH7w[W9KSzVyPUCuNVI4KM7:TR?= NGrVcIQzODFyOEOzPC=>

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
p-AURKA(T288) / p-EIF4E(S209) / c-Myc; 

PubMed: 28073841     


Inhibition of AURKA with alisertib downregulated p-EIF4E (S209) and c-MYC protein levels as assayed by Western blotting.

phospho-Aurora A / Aurora B; 

PubMed: 22863010     


MLN8237differentially inhibited phosphorylation of Aurora kinases. CMK cells were incubated with 0.1 µM paclitaxel for 18 hr, then DMSO or MLN8237 was added and incubated for 2 hr. The degree of phosphorylation of the Aurora kinases in each sample was determined by Western blot.

H3S10P / H3K27me2 / H3K27me3 / H3K9me2 / H3AcK / H4K16Ac; 

PubMed: 29477140     


THP-1 cells were treated with alisertib or DMSO for 48 h. The levels of histone modifications were detected by western blot analysis with the indicated antibodies. H3 was used as a loading control.

28073841 22863010 29477140
Growth inhibition assay
Cell viability; 

PubMed: 25632225     


PANC-1 and BxPC-3 cells were treated with ALS at concentrations ranging from 0.1 μM to 50 μM for 24 hours. The viability of PANC-1 and BxPC-3 cells determined by MTT assay. ALS, alisertib.

25632225
Immunofluorescence
acetylated α-tubulin / γ-tubulin; 

PubMed: 29401581     


Representative immunofluorescence (IF) image and graph in human PKD1-mutant WT9-7, WT9-12 cells or hTERT-RPE1 (RPE1) cells after 2 hours treatment with vehicle, ganetespib , or alisertib to inhibit AURKA, or combination of alisertib and ganetespib. acetylated α-tubulin (red); γ-tubulin (green); DAPI (blue). Scale bars, 5 μm.

E-cadherin / β-catenin / vimentin / p-SMAD5; 

PubMed: 23334326     


Immunofluorescence analysis of CD24 (-/low) cells treated with1 μM MLN8237 for 48 and 72 h showing reversion of EMT. E-cadherin and p-SMAD5 were labeled in red, β-catenin and vimentin were labeled in green, and DNA was labeled in blue with Hoechst dye.

Centrin-2 / tubulin; 

PubMed: 30899434     


Following inhibition of Aurora A kinase activity with 100 nM alisertib, cells with two or excess centrosomes similarly exhibit disorganized mitotic spindles. Cells with extra centrosomes are efficiently clustered into bipolar spindles prior to anaphase onset while those with supernumerary centrosomes undergo multipolar mitoses. Centrin-2, a marker of centrioles is shown in green, tubulin in red, and chromatin in blue. AurA inhibitor: alisertib.

phospho-Aurora A(T288); 

PubMed: 20382844     


MM1.S cells were treated with DMSO or MLN8237 (0.5μM) for 24 hours and then stained with anti-phospho (Thr288)-Aurora-A kinase antibody (red), αtubulin (green), and DNA (blue). Overlapping localization is shown in the merged images. Arrow indicates Aurora-A autophosphorylation on Thr288 in the centrosome (original magnification ×40). Magnified single mitotic cell image is shown in the right panel. 

29401581 23334326 30899434 20382844
体内研究 MLN8237口服处理，显著降低肿瘤负担，按15 mg/kg 和30 mg/kg剂量处理肿瘤生长抑制率(TGI) 分别为42%和80%,且与对照组相比，延迟小鼠寿命。[2] MLN8237 (30 mg/kg) 与Cisplatin (2 mg/kg) 联用作用于FLO-1移植瘤，与单独用药相比，抗癌活性增强，伴随着Ki-67表达受抑制，细胞核p73蛋白和cleaved caspase 3表达增强。[3]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验：[1]
+ 展开

Aurora A放射性闪光板酶实验:

进行Aurora A放射性闪光板酶实验，测定体外MLN8237抑制程度。在Sf9细胞中表达重组Aurora A，然后使用GST亲和层析进行纯化。Aurora A 肽底物与生物素联合形成生物素-GLRRASLG。在50 mM Hepes (pH 7.5), 10 mM MgCl2, 5 mM DTT, 0.05% Tween-20, 2 μM 肽底物, 3.3 μCi/mL [γ-33 P]ATP 2 μM, 和浓度不断增高的MLN8237 的混合物中进行Aurora A激酶 (5 nM)实验。
细胞实验：[2]
+ 展开
  • Cell lines: MM1.S, MM.1R, LR5, RPMI 8226, DOX40, OPM1, OPM2, INA6, 和U266
  • Concentrations: 溶于DMSO,终浓度为~10 μM
  • Incubation Time: 24, 48, 和72小时
  • Method: 使用不同浓度MLN8237处理细胞24, 48,和72小时。通过MTT实验测定细胞活力，通过测定 3[3H]-胸甘渗透而测定细胞增殖。为了分析细胞周期，使用70%乙醇在-20oC下使细胞通透，然后与50 μg/mL PI 和20 单位/mL RNase-A温育。 通过流式细胞仪使用 BDFACS-Canto II和FlowJo软件分析DNA含量。 为了测定凋亡和衰老，使用异硫氰酸荧光素-annexin V和PI对细胞进行染色。通过流式细胞仪使用 BDFACS-Canto II和FlowJo软件测定凋亡细胞。
    (Only for Reference)
动物实验：[2]
+ 展开
  • Animal Models: 皮下接种 MM1.S 细胞的SCID鼠
  • Formulation: 在10% 2-羟丙基-β-环糊精/1％碳酸氢钠中配制
  • Dosages: ~30 mg/kg/day
  • Administration: 口服处理
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 27 mg/mL (52.03 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)：
5%DMSO+30% PEG300+5%Tween-80+ddH2O
 8mg/mL

* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 518.92
化学式

C27H20ClFN4O4
CAS号 1028486-01-2
储存条件 powder
in solvent
别名 N/A

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液，使用的计算公式为：

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量：

总分子量：g/mol

注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02812056 Withdrawn Malignant Neoplasms of Digestive Organs|Malignant Neoplasms of Female Genital Organs|Malignant Neoplasms of Lip Oral Cavity and Pharynx|Malignant Neoplasms of Male Genital Organs M.D. Anderson Cancer Center|Millennium Pharmaceuticals Inc. September 2016 Phase 1
NCT02719691 Recruiting Metastatic Breast Cancer|Solid Tumors University of Colorado Denver May 13 2016 Phase 1
NCT02367352 Terminated Advanced Solid Tumors|Ovarian Cancer|Small Cell Lung Cancer Millennium Pharmaceuticals Inc.|Takeda March 19 2015 Phase 1

技术支持

在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题，请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1：

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

  • 回答：

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

Selleck产品目录册

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

  • 泛Aurora Kinase抑制剂

    Danusertib (PHA-739358) : Pan-Aurora kinase inhibitor, Aurora A/B/C, IC50=13 nM/79 nM/61 nM.

  • 泛Aurora Kinase抑制剂

    SNS-314 Mesylate : Pan-Aurora kinase inhibitor, Aurora A/B/C, IC50=9 nM/31 nM/3 nM.

  • 活性最高的Aurora Kinase抑制剂

    MK-5108 (VX-689) : Aurora A, IC50=0.064 nM.

  • 用于临床的Aurora Kinase抑制剂

    VX-680 (Tozasertib, MK-0457) : Phase II for Advanced Non-Small Cell Lung Cancer (NSCLC).

  • 经典的Aurora Kinase抑制剂

    Hesperadin : Potently inhibits Aurora B with IC50 of 250 nM.

相关Aurora Kinase产品

  • Ro-3306 New

    RO-3306是一种ATP竞争性的选择性 CDK1 抑制剂，Ki 为20 nM，选择性是其他各种人类激酶的15倍多。

  • CCG-1423 New

    CCG-1423是一种特定的 RhoA 通路抑制剂，能够抑制SRF介导的转录。

  • ML141 New

    ML141是Rho家族GTPase cdc42的一种有效的，选择性可逆非竞争性抑制剂，IC50为200 nM。对cdc42比对其他Rho家族中的GTPases(如Rac1, Rab2, Rab7)更有选择性。

  • Barasertib (AZD1152-HQPA|AZD2811)

    Barasertib (AZD1152-HQPA)是一种高度选择性的Aurora B抑制剂，无细胞试验中IC50为0.37 nM，作用于Aurora B比作用于Aurora A选择性高3700倍左右。

  • Tozasertib (VX-680, MK-0457)

    Tozasertib (VX-680, MK-0457)是一种pan-Aurora抑制剂，对Aurora A作用最强，无细胞试验中Kiapp为0.6 nM，而对Aurora B/Aurora C的作用较弱，对Aurora A选择性比其他55种激酶高100倍。Phase 2。

  • Danusertib (PHA-739358)

    Danusertib (PHA-739358)是一种Aurora kinase抑制剂，作用于Aurora A/B/C，无细胞试验中IC50为13 nM/79 nM/61 nM，适度有效作用于Abl，TrkA，c-RET和FGFR1，对Lck，VEGFR2/3，c-Kit，CDK2等作用效果稍弱。Phase 2。

  • ZM 447439

    ZM 447439是一种选择性的，ATP竞争性Aurora A和Aurora B抑制剂，IC50分别为110 nM和130 nM，作用于Aurora A/B比作用于MEK1， Src， Lck选择性高8倍，对CDK1/2/4， Plk1， Chk1等几乎没有作用效果。

    Features:ZM-447439是Aurora选择性ATP竞争性抑制剂

  • MLN8054

    MLN8054是一种有效的，选择性Aurora A抑制剂，在Sf9昆虫细胞中IC50为4 nM，作用于Aurora A比作用于Aurora B选择性高40倍。Phase 1。

    Features:MLN8054是有效的 Aurora A激酶选择性抑制剂。

  • MK-5108 (VX-689)

    MK-5108 (VX-689)是一种高选择性的Aurora A抑制剂，无细胞试验中IC50为0.064 nM，作用于Aurora A比作用于Aurora B/C选择性高220和190倍，作用于TrkA的选择性低100倍。Phase 1。

  • Aurora A Inhibitor I (TC-S 7010)

    Aurora A Inhibitor I是一种新型有效的，选择性Aurora A抑制剂，无细胞试验中IC50为3.4 nM，作用于Aurora A比作用于Aurora B选择性高1000倍。

    Features:Aurora A Inhibitor I 是2,4-二苯胺嘧啶抑制剂。

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID