Alisertib (MLN8237)

For research use only. Not for use in humans.

目录号：S1133 中文名称：阿利色替

CAS No. 1028486-01-2

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。Alisertib 可诱导细胞周期阻滞、细胞凋亡与自噬。Phase 3。

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购买数量

10mM (1mL in DMSO)	RMB 1375.12	现货
5mg	RMB 983.87	现货
10mg	RMB 1725.78	现货
50mg	RMB 5505.84	现货
200mg	RMB 14496.3	现货
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客户使用Selleck生产的Alisertib (MLN8237)发表文献297篇：

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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

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	NFruOXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MUKwMlUh\|ryP	M2rLSVczKGh?	M3TxcWROW09?	M1;aVmlEPTB;MD6wOEDPxE1?	NEfMRlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN\|Y3QDR:L3G+
LS174T	M1;T[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MYSwMlUh\|ryP	NW\TSodTPzJiaB?=	MknzSG1UVw>?	MYrJR\|UxRTBwMEWg{txO	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
T84	NYr5XYlWT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MXywMlUh\|ryP	NFqxSZM4OiCq	M2OzemROW09?	MXTJR\|UxRTBwMEmg{txO	MnfKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
LS180	NFTIclJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M3zl[\|AvPSEQvF2=	NVO0XWp5PzJiaB?=	MV3EUXNQ	M4LhVWlEPTB;MTFOwG0>	NHn4b4k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN\|Y3QDR:L3G+
SW948	MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Ml7MNE42KM7:TR?=	M17teFczKGh?	M3fEUmROW09?	NUPvNplMUUN3ME2xJO69VQ>?	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
HCT15	M2T2cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NV;xfW53OC53IN88US=>	NIPTeHM4OiCq	M{PrTmROW09?	NGLt[4ZKSzVyPECuOEDPxE1?	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
DLD-1	MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NIjGVYMxNjVizszN	NYjCTmxEPzJiaB?=	MUnEUXNQ	Ml\1TWM2ODxyLkig{txO	NWT1cW9YRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xN\|Y3QDRpPkK2NVM3Pjh2PD;hQi=>
MIP-101	MkC5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NV\kNGVDOC53IN88US=>	M1\5N\|czKGh?	M2LvfGROW09?	NITCUpNKSzVyPUGg{txO	M{TrXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUO2Olg1Lz5{NkGzOlY5PDxxYU6=
SNU1544	MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NYj1bppLOC53IN88US=>	NWfJNHl{PzJiaB?=	NUGzRoJjTE2VTx?=	NVzLW4VGUUN3ME2xJO69VQ>?	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
OCI-Ly10	MV7DfZRwfG:6aXOgRZN{[Xl?		MnvRO\|IhcA>?	MknFSG1UVw>?	MlPvTWM2OD1yLkC1PEDPxE1?	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
SU-DHL2	M3HxVWN6fG:2b4jpZ{BCe3OjeR?=		MkDqO\|IhcA>?	M4G0XGROW09?	M3rtcmlEPTB;MD6wNUDPxE1?	NHH4UpU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
OCI-LY7	M1u3XGN6fG:2b4jpZ{BCe3OjeR?=		NUnBSlBIPzJiaB?=	M3HTZmROW09?	MXHJR\|UxRTBwMEixJO69VQ>?	MmXuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
SU-DHL6	MYXDfZRwfG:6aXOgRZN{[Xl?		NGjUOIk4OiCq	MUPEUXNQ	M{PvVGlEPTB;MD60PFIh\|ryP	NEfCZpY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
Jeko-1	NV\WdJMxS3m2b4TvfIlkKEG\|c3H5		MmryO\|IhcA>?	NX\Ic4M4TE2VTx?=	MV\JR\|UxRTBwMEK5JO69VQ>?	NXXU[4xORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
JVM-2	NEPOXm5EgXSxdH;4bYMhSXO\|YYm=		NH;mS2s4OiCq	NVryfYJxTE2VTx?=	MkjmTWM2OD1yLkCxJO69VQ>?	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
Rec-1	NVfZOYx5S3m2b4TvfIlkKEG\|c3H5		MoPtO\|IhcA>?	M1u0WmROW09?	MkK1TWM2OD1yLkC4O{DPxE1?	M3rFTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
Z-138	MYLDfZRwfG:6aXOgRZN{[Xl?		M4nDO\|czKGh?	MmDqSG1UVw>?	MmDLTWM2OD1yLkCxN{DPxE1?	NWTnRndwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
H9	NGfnSlhEgXSxdH;4bYMhSXO\|YYm=		NGDsOmE4OiCq	MnXMSG1UVw>?	NYnIdZN{UUN3ME2wMlYh\|ryP	NFz0PI49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
HH	NXP1ZZhIS3m2b4TvfIlkKEG\|c3H5		MlPQO\|IhcA>?	NUXadol[TE2VTx?=	M1i2OGlEPTB;MD63JO69VQ>?	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
DND41	MkHRR5l1d3SxeHnjJGF{e2G7		MmLyO\|IhcA>?	NWLOOGRTTE2VTx?=	MnTDTWM2OD1yLkGg{txO	NV;Wd244RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
CCL119	M3jwOmN6fG:2b4jpZ{BCe3OjeR?=		NVLnWI5tPzJiaB?=	NIjyWGlFVVOR	MVTJR\|UxRTBwME[yJO69VQ>?	MoC2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
J.Cam 1.6	M2G2b2N6fG:2b4jpZ{BCe3OjeR?=		MoO2O\|IhcA>?	M4PBbWROW09?	MlS5TWM2OD1yLkGwOUDPxE1?	Mn7uQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
Sup-T1	M1fxWmN6fG:2b4jpZ{BCe3OjeR?=		NHK3UWw4OiCq	NGXOZ3FFVVOR	M2Xie2lEPTB;Mj6xOFIh\|ryP	MmHPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
Tib 152	NVnVfmhrS3m2b4TvfIlkKEG\|c3H5		NFvTOWE4OiCq	MUPEUXNQ	Ml6wTWM2OD1yLkig{txO	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
MCF7	MoK1SpVv[3Srb36gRZN{[Xl?	MkXZOUDPxE1?	NXvrOnAzOjRiaB?=	NV30NlFHTE2VTx?=	MYPJcoR2[2W\|IFeyM20h[XK{ZYP0	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MDA-MB-231	MVXGeY5kfGmxbjDBd5NigQ>?	M4[xc\|Uh\|ryP	MX[yOEBp	NXrGcJQyTE2VTx?=	MkPBTY5lfWOnczDHN{9OKGG{cnXzeC=>	NXPOZnlwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MCF7	M2jiSmZ2dmO2aX;uJGF{e2G7	MljEOUDPxE1?	NH2yXWszPCCq	MnXFSG1UVw>?	NWrXXmRqTGWlcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=>	Ml;oQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MCF7	MnPHSpVv[3Srb36gRZN{[Xl?	NI\ncVY2KM7:TR?=	MYOyOEBp	NYTle2hUTE2VTx?=	NELKdGZF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOg>?	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	MnuzSpVv[3Srb36gRZN{[Xl?	MVq1JO69VQ>?	NID6RXkzPCCq	NYmzd4JOTE2VTx?=	NEPiSY1F\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gZ5lkdGmwIFKx	M1HsT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MCF7	M{e2RmZ2dmO2aX;uJGF{e2G7	NFyy[lY2KM7:TR?=	M13hPFI1KGh?	MVnEUXNQ	NHfhcWtKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFIyKFejZkGvR4lxOQ>?	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	NIW2N3hHfW6ldHnvckBCe3OjeR?=	MUO1JO69VQ>?	Mle0NlQhcA>?	MYXEUXNQ	MXXJcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF?	M1HoZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	NFLDfJJHfW6ldHnvckBCe3OjeR?=	NYX0PFFGPSEQvF2=	MUeyOEBp	M{n3S2ROW09?	NYLZZ2JOTGWlcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=>	NGXhTlU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	M3rOPGZ2dmO2aX;uJGF{e2G7	NXq4eotOOSEQvF2=	NH23[IQzPCCq	NF;pW2lFVVOR	NYDRRmp3UW6lcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJGNFUzJ?	NFLFXm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	NX3zVHh6TnWwY4Tpc44hSXO\|YYm=	MmXDOUDPxE1?	MUOyOEBp	NX;hboNkTE2VTx?=	M1TwSmRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG=	NECzdGw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	Mo\JSpVv[3Srb36gRZN{[Xl?	NX7kTpVkPSEQvF2=	M37OPVI1KGh?	MmC1SG1UVw>?	MnHwTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE>	MnHEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MDA-MB-231	MkO0SpVv[3Srb36gRZN{[Xl?	M4rqUlUh\|ryP	M4PSO\|I1KGh?	MoC1SG1UVw>?	M3zXVWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?=	MnflQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MDA-MB-231	M1PFbGZ2dmO2aX;uJGF{e2G7	M1rEVlUh\|ryP	NUXQXGc1OjRiaB?=	NF;JU5BFVVOR	NWDLRpdzUW6lcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJJA2Ow>?	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	NFHFS3ZCeG:ydH;zbZMhSXO\|YYm=	Mn7QOUDPxE1?	MmXzNlQhcA>?	MWPEUXNQ	M{\2XWlv\HWlZYOgZZBweHSxdHnjJIRm[XSq	NEfrdmw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	NVHLRnRCSXCxcITvd4l{KEG\|c3H5	MU[1JO69VQ>?	M2LDOlI1KGh?	MkHiSG1UVw>?	NHPyRZBKdmS3Y3XzJIFxd3C2b4TpZ{Bl\WG2aB?=	NWPRbnRkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MCF7	NFPoXo1HfW6ldHnvckBCe3OjeR?=	MmXONUDPxE1?	M1XSZVczKGh?	NH[4O4tFVVOR	MUHJcoR2[2W\|IHH1eI9xcGGpaXOg[IVifGh?	NWqyfVFMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MDA-MB-231	NFGy[WNHfW6ldHnvckBCe3OjeR?=	M4nsb\|Eh\|ryP	Ml7rO\|IhcA>?	MV3EUXNQ	Mor2TY5lfWOnczDheZRweGijZ3njJIRm[XSq	NFTyPFk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
U-2 OS	MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MWe1NEDPxE1?	M1;2R\|I1KGh?	MVfEUXNQ	MnixTWM2OD1zNj62JO69VQ>?	NVnKbXhLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3PVI5OTFpPkK1O\|kzQDFzPD;hQi=>
MG-63	M3jCPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NWLtc4k5PTBizszN	MoS3NlQhcA>?	MXXEUXNQ	NUS4bFFQUUN3ME25MlUh\|ryP	NF\YXm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe5NlgyOSd-MkW3PVI5OTF:L3G+
U-2 OS	NYj4O5RwSXCxcITvd4l{KEG\|c3H5	NXPhOnpiPSEQvF2=	MXSyOEBp	NF20N4dFVVOR	MXXJcoR2[2W\|IHHwc5B1d3SrYzDj[YxtKGSnYYTo	MorrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5OUK4NVEoRjJ3N{myPFEyRC:jPh?=
MG-63	NGHaXnpCeG:ydH;zbZMhSXO\|YYm=	NX[3U\|FNPSEQvF2=	M3HxVVI1KGh?	MVzEUXNQ	NGPhSIVKdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRp	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd7MkixNUc,OjV5OUK4NVE9N2F-
U-2 OS	M{jkOGZ2dmO2aX;uJGF{e2G7	MkPVOUDPxE1?	M3eweFI1KGh?	MX7EUXNQ	NH;PXZZRem:vb4Tld{BifXSxcHjh[4lkKGOnbHyg[IVifGh?	NVPtNIQ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3PVI5OTFpPkK1O\|kzQDFzPD;hQi=>
MG-63	M4LNRWZ2dmO2aX;uJGF{e2G7	NHuyZ2U2KM7:TR?=	NGnTVoQzPCCq	MX;EUXNQ	NVziU2V2WHKxbX;0[ZMh[XW2b4DoZYdq[yClZXzsJIRm[XSq	MojSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5OUK4NVEoRjJ3N{myPFEyRC:jPh?=
PANC-1	MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MW[1NEDPxE1?	NF;lWpkzPCCq	MYPEUXNQ	Mln6TWM2OD15LkGg{txO	M1:2dFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkOyNlI2Lz5{NU[zNlIzPTxxYU6=
BxPC-3	NVroZ2lwT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NInFUZY2OCEQvF2=	NYq4fXMyOjRiaB?=	MXTEUXNQ	NYDsTFVRUUN3ME22Mlgh\|ryP	NWn5bJdZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2N\|IzOjVpPkK1OlMzOjJ3PD;hQi=>
PANC-1	MoPXSpVv[3Srb36gRZN{[Xl?	MlHoOUDPxE1?	MVuyOEBp	M4DZVGROW09?	NG\MUm5KdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V?	NYDQTHJjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2N\|IzOjVpPkK1OlMzOjJ3PD;hQi=>
BxPC-3	NWm2XXZbTnWwY4Tpc44hSXO\|YYm=	MUS1JO69VQ>?	MlTvNlQhcA>?	MW\EUXNQ	NHzNSI9KdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V?	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ\|MkKyOUc,OjV4M{KyNlU9N2F-
PANC-1	NYfye5Q{TnWwY4Tpc44hSXO\|YYm=	NXrpN4RmPSEQvF2=	M4mzZVI1KGh?	NVH3T4MzTE2VTx?=	MVTJcoR2[2W\|IHH1eI9xcGGpaXOgZ4VtdCCmZXH0bC=>	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ\|MkKyOUc,OjV4M{KyNlU9N2F-
BxPC-3	NV\0TYFxTnWwY4Tpc44hSXO\|YYm=	NUjOSmxMPSEQvF2=	NIXqO\|UzPCCq	MWHEUXNQ	M4THdWlv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ\|MkKyOUc,OjV4M{KyNlU9N2F-
SKOV3	NInhOIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M4TOSlExOCEQvF2=	MUSyOEBp	M1j2N2ROW09?	NVT0TmNuUUN3ME2yNE41QCEQvF2=	NI\xSng9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOFc2OCd-MkW2NlQ4PTB:L3G+
OVCAR4	MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MkLENVAxKM7:TR?=	MoDqNlQhcA>?	Ml7xSG1UVw>?	MVvJR\|UxRTJ{LkGzJO69VQ>?	M4XVZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkK0O\|UxLz5{NU[yOFc2ODxxYU6=
SKOV3	NX;Sfm5YTnWwY4Tpc44hSXO\|YYm=	M4TSPVUh\|ryP	MVe3NkBp	MkPjSG1UVw>?	NWnvXZpvUW6mdXPld{BIOi:PIHHydoV{fA>?	NWHMd5oxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NlQ4PTBpPkK1OlI1PzVyPD;hQi=>
OVCAR4	NYHqN3ZqTnWwY4Tpc44hSXO\|YYm=	NVTPeGRXPSEQvF2=	MonpO\|IhcA>?	M324OmROW09?	MlPCTY5lfWOnczDHNk9OKGG{cnXzeC=>	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ{NEe1NEc,OjV4MkS3OVA9N2F-
SKOV3	NYDkNHBHSXCxcITvd4l{KEG\|c3H5	M3P2XlUh\|ryP	NYr3W4xyOjRiaB?=	NF\qfI5FVVOR	MkTTTY5lfWOnczDhdI9xfG:\|aYO=	M1ztTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkK0O\|UxLz5{NU[yOFc2ODxxYU6=
OVCAR4	NX3MenVoSXCxcITvd4l{KEG\|c3H5	MmPNOUDPxE1?	NXr5NnZpOjRiaB?=	NUPHU5hJTE2VTx?=	M1O0WWlv\HWlZYOgZZBweHSxc3nz	Mme0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4MkS3OVAoRjJ3NkK0O\|UxRC:jPh?=
AGS	NXLGOVVJT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M2G5RlI2KM7:TR?=	NHzUdZgzPCCq	MWTEUXNQ	M2HQNGlEPTB;MUmuNFkh\|ryP	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZyOUmyN{c,OjV4MEm5NlM9N2F-
NCI-N78	NF30SphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	Mki1NlUh\|ryP	M4TiUlI1KGh?	NEnwTXVFVVOR	Mlj2TWM2OD1{Nj6zN{DPxE1?	M1PUTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkC5PVI{Lz5{NU[wPVkzOzxxYU6=
AGS	NUTRTXJ{SXCxcITvd4l{KEG\|c3H5	M2nFOFUh\|ryP	MkXONlQhcA>?	M3z6O2ROW09?	NW\SN2c2UW6mdXPld{BieG:ydH;zbZM>	NFW5ZXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[wPVkzOyd-MkW2NFk6OjN:L3G+
NCI-N78	NVrYV\|FmSXCxcITvd4l{KEG\|c3H5	NWTWWmRCPSEQvF2=	MlrBNlQhcA>?	MX;EUXNQ	NEDDNoFKdmS3Y3XzJIFxd3C2b4Ppdy=>	NFj2dnE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[wPVkzOyd-MkW2NFk6OjN:L3G+
AGS	NGfHNIxHfW6ldHnvckBCe3OjeR?=	MXK1JO69VQ>?	MkKyNlQhcA>?	NHG0TpJFVVOR	NWXLR3pEUW6mdXPld{B1cGViYYX0c5Bp[We7	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZyOUmyN{c,OjV4MEm5NlM9N2F-
NCI-N78	MmfzSpVv[3Srb36gRZN{[Xl?	MVK1JO69VQ>?	MWOyOEBp	M3XG[2ROW09?	NVm0O3hLUW6mdXPld{B1cGViYYX0c5Bp[We7	NEfEfos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[wPVkzOyd-MkW2NFk6OjN:L3G+
HSC-3	NY[4OFR5T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NFzXR4syKM7:TR?=	NVf3dJZFPDhiaB?=		Mn7wTWM2OD1yLkW0JO69VQ>?	M{f1SlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{[2NVQ{Lz5{NUO2OlE1OzxxYU6=
GB30	MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M1zLeFEh\|ryP	NWXsN5o5PyCm	MlLhSG1UVw>?	MUHJR\|UxRTBwMEGxJO69VQ>?	Ml\TQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVzME[0NlgoRjJ3MUC2OFI5RC:jPh?=
GB9	Ml;qS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MXWxJO69VQ>?	M17QVlch\A>?	NH;qWmZFVVOR	M{nJXWlEPTB;MD6wNlQh\|ryP	NXH2UpltRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWxNFY1OjhpPkK1NVA3PDJ6PD;hQi=>
GB169	Ml7pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M1vablEh\|ryP	MVy3JIQ>	MnTESG1UVw>?	NXT0c\|d2UUN3ME2wMlA{OiEQvF2=	M{LTblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MUC2OFI5Lz5{NUGwOlQzQDxxYU6=
T24	NVPtb2M1TnWwY4Tpc44hSXO\|YYm=	NIfUd\|IyKM7:TR?=	NE\nZnA1QCCq	MkPuSG1UVw>?	MVLJcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	M2j6ZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NECzOlM{Lz5{M{SwN\|Y{OzxxYU6=
RT4	M1The2Z2dmO2aX;uJGF{e2G7	NXjve213OSEQvF2=	NEDJWIU1QCCq	M1PUc2ROW09?	NET2fZZKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	NWXoSoM{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0NFM3OzNpPkKzOFA{PjN\|PD;hQi=>
UM-UC-3	NVG1S49CTnWwY4Tpc44hSXO\|YYm=	MnThNUDPxE1?	M2fveVQ5KGh?	NFj2PFNFVVOR	MnfBTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzRyM{[zN{c,OjN2MEO2N\|M9N2F-
T24	M2myPGFxd3C2b4Ppd{BCe3OjeR?=	M3uxR\|MvOTZizszN	MY[5OkBp	MV7EUXNQ	NWjRfY5FUUN3ME2wMlA{ODZizszN	M1P2NVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NECzOlM{Lz5{M{SwN\|Y{OzxxYU6=
RT4	MX7BdI9xfG:\|aYOgRZN{[Xl?	MV[zMlE3KM7:TR?=	NFPMdpY6PiCq	NE[3VotFVVOR	M4O0NmlEPTB;MD6xNVk5KM7:TR?=	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzRyM{[zN{c,OjN2MEO2N\|M9N2F-
UM-UC-3	NIXrRnBCeG:ydH;zbZMhSXO\|YYm=	MWezMlE3KM7:TR?=	MoWwPVYhcA>?	M3\ZWGROW09?	MlmyTWM2OD1yLkC0OFkh\|ryP	NYf3[HhlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0NFM3OzNpPkKzOFA{PjN\|PD;hQi=>
OVCAR-5	MkP6SpVv[3Srb36gRZN{[Xl?	MlHZOVAhdk1?			NHXGV5ZKdmirYnn0d{Bk\WyuIH3p[5JifGmxbh?=	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN\|NEOyO{c,OjN\|M{SzNlc9N2F-
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SKM-1	MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NU\nVoxvOyEQvF2=	NH;PT2c4OiCq		MXTEbY1qdmm\|aHXzJINmdGxidnnhZoltcXS7	NULETlk{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PFgzPDlpPkKyOFg5OjR7PD;hQi=>
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OCL-AML2	M1\Kfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NGnVZ\|A{KM7:TR?=	MmrsO\|IhcA>?		NVTIVplHTGmvaX7pd4hmeyClZXzsJJZq[WKrbHn0fS=>	NWmweWpCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0PFgzPDlpPkKyOFg5OjR7PD;hQi=>
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HF2359	MUnDfZRwfG:6aXOgRZN{[Xl?	NYixcplSOTByIN88US=>	MonDNlQhcA>?	MkfBSG1UVw>?	M1SydmlEPTB;MD6wOlAh\|ryP	NHrQeoo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkK3OFM6QSd-MkKyO\|Q{QTl:L3G+
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TC-32	MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NUTPS5ZLOTBizszN	NV;hdlZXQTZiaB?=	MWrEUXNQ	Mlz6TWM2OD1yLkCzPUDPxE1?	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTR2OEW5NUc,OjF2NEi1PVE9N2F-
TC-71	Mn3US5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NIX2fVAyOCEQvF2=	NYHKW3pnQTZiaB?=	NF3mXZZFVVOR	MWnJR\|UxRTBwMUCyJO69VQ>?	NIDTNY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS0PFU6OSd-MkG0OFg2QTF:L3G+
SK-N-MC	MmX6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NV;SSGpIOTBizszN	NF;MTmc6PiCq	MmXnSG1UVw>?	NXHub25YUUN3ME2wMlA4OiEQvF2=	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTR2OEW5NUc,OjF2NEi1PVE9N2F-
CHLA-9	MoW2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M13CblExKM7:TR?=	MV[5OkBp	NF32WXlFVVOR	MlviTWM2OD1yLkCxPEDPxE1?	M{S1RlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNES4OVkyLz5{MUS0PFU6OTxxYU6=
CHLA-10	NH;KXXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	Mke0NVAh\|ryP	NYL5SJl6QTZiaB?=	NF70d5JFVVOR	NGTZXJJKSzVyPUCuNFYxKM7:TR?=	NHLjbHE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS0PFU6OSd-MkG0OFg2QTF:L3G+
CHLA-25	M1zsemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NIrlNYoyOCEQvF2=	MoHFPVYhcA>?	NVPlPXZkTE2VTx?=	MV;JR\|UxRTBwMU[4JO69VQ>?	M2faNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNES4OVkyLz5{MUS0PFU6OTxxYU6=
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PC14	Mo\KRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		MVq3NkBpenN?		MXnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFCFMUSgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFeVVEigZZN{[XluIFnDOVAhRSByLkG3JO69VS5?	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ{NU[xO{c,OjV4MkW2NVc9N2F-
HT-29	NGTuO4hCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NYDVd5h4PzJiaILz		M{eySmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSGStNlkh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IGfTWFgh[XO\|YYmsJGlEPTBiPTCwMlM{KM7:TT6=	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ{NU[xO{c,OjV4MkW2NVc9N2F-
HCT15	M3HJOmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MYG3NkBpenN?		MYPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFVEG1JINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCZU2S4JIF{e2G7LDDJR\|UxKD1iMD63OEDPxE1w	M37WN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkK1OlE4Lz5{NU[yOVYyPzxxYU6=
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HCT116	NVHSeW9LTnWwY4Tpc44h[XO\|YYm=				MXnJcohq[mm2aX;uJI9nKGG3cn;yZUBscW6jc3WgRUBifXSxcHjvd5Bpd3K7bHH0bY9vKGG2IGSyPFghcW5iaIXtZY4hUEOWMUG2JINmdGy\|IHL5JIludXWwb3\seY9z\XOlZX7j[UBidmGueYPpd{whUUN3MDC9JFAvODB5IN88UU4>	M2TuOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUCxOVY1Lz5{NkGwNVU3PDxxYU6=
HCT116	M1fZUmN6fG:2b4jpZ4l1gSCjc4PhfS=>				MX3DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[nliQoLkWUBqdmOxcoDvdoF1cW:wIHHzd4F6NCCJSUWwJF0hOC5yMzFOwG0v	MnfpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMEG1OlQoRjJ4MUCxOVY1RC:jPh?=
HCT116	MUnGeY5kfGmxbjDhd5NigQ>?				NFLjN3RKdmirYnn0bY9vKG:oIHH1do9z[SCtaX7hd4UhSiCrbjDoeY1idiCKQ2SxNVYh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDobZN1d26nIFizJJBpd3OyaH;yfYxifGmxbjDifUBqdW23bn;mcJVwemW\|Y3XuZ4Uh[W6jbInzbZMtKEmFNUCgQUAyNjVizszNMi=>	NGXBcnA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGwNVU3PCd-Mk[xNFE2PjR:L3G+
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HeLa Kyoto	MljoSpVv[3Srb36gZZN{[Xl?		MmLKNlAhcHK\|		NVLmZ\|B3UW6qaXLpeIlwdiCxZjDBeZJwemFiQjDrbY5ie2ViaX6gbJVu[W5iSHXMZUBMgW:2bzDj[YxteyCjc4Pld5Nm\CCjczDl[oZm[3Rib36g[Il{fHKrYoX0bY9vKG:oIIDod5Bpdy2qaYP0c45mKEh\|IIPldlExKGyndnXsJIlv[3WkYYTl[EBnd3JiMkCgbJJ{NCCLQ{WwJF0hOC5yMEG1JO69VS5?	MknlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd\|OUGxN\|MoRjJ5M{mxNVM{RC:jPh?=
HeLa Kyoto	NWOxc3RvTnWwY4Tpc44h[XO\|YYm=		NIjaW5IzOCCqcoO=		M4LBN2lvcGmkaYTpc44hd2ZiQYXyc5JiKEFia3nuZZNmKGG3dH;wbI9{eGixconsZZRqd25iYYSgWIhzOjh6IHnuJIh2dWGwIFjlUIEhU3mxdH:gZ4VtdHNiaX7jeYJifGWmIH\vdkAzOCCqcoOsJGlEPTBiPTCwMlAxPjdizszNMi=>	NIXnZ4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{O5NVE{Oyd-MkezPVEyOzN:L3G+
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MDA-MB-231	NH\5[4hHfW6ldHnvckBie3OjeR?=	NG[3PJoyKHWP	MoK0OFghcHK\|		NFHJVlFKdmS3Y4Tpc44hd2ZiY3jyc41we2:vZTDhcIlodm2nboSg[IVn\WO2czDpckBpfW2jbjDNSGEuVUJvMkOxJINmdGy\|IHH0JFEhfU1iYX\0[ZIhPDhiaILzJIJ6KESDUFmgd5RicW6rbnegZoF{\WRiaX3teY5w\my3b4Lld4NmdmOnIHHzd4F6	NFfDcWs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUO1PFE1Pyd-MkmzOVgyPDd:L3G+
MDA-MB-231	Ml60SpVv[3Srb36gZZN{[Xl?	NIe5OIkyKHWP	NFr1V2Y1QCCqcoO=		M3uwNWlv\HWldHnvckBw\iCjYnXydoFvfCC\|cHnu[IxmKG[xcn3heIlwdiC5aYToJJRzcXCxbHHyJIFv\CC2ZYTyZZBwdGG{IH;jZ5VzemWwY3WgbY4hcHWvYX6gUWRCNU2ELUKzNUBk\WyuczDheEAyKHWPIHHmeIVzKDR6IHjyd{BjgSCGQWDJJJN1[WmwaX7nJIJie2WmIHntcZVvd2[udX;y[ZNk\W6lZTDhd5NigQ>?	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTN3OEG0O{c,Ojl\|NUixOFc9N2F-
MDA-MB-231	M2K2TmZ2dmO2aX;uJIF{e2G7	M3vrZ\|AvPSC3TR?=	MmDxOFghcHK\|		MnXDTY5pcWKrdHnvckBw\iCjbIDoZU11fWK3bHnuJIlvKGi3bXHuJG1FSS2PQj2yN\|Eh[2WubIOgZZN{\XO\|ZXSgZZMh[WKxbHnzbI1mdnRib3[gdoVofWyjcjDsc4NifGmxbjDv[kBxem:2ZXnuJIF1KDBwNTD1UUBi\nSncjC0PEBpenNiYomgSGFRUSC\|dHHpcolv\yCkYYPl[EBqdW23bn;mcJVwemW\|Y3XuZ4Uh[XO\|YYm=	Mki4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl\|NUixOFcoRjJ7M{W4NVQ4RC:jPh?=
MDA-MB-231	NHPm[49HfW6ldHnvckBie3OjeR?=	M33mcVAvPSC3TR?=	MYq0PEBpenN?		NXzKWW1rUW6qaXLpeIlwdiCxZjDBWXJMSSCrbjDoeY1idiCPRFGtUWIuOjNzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHHic4xqe2ivZX70JI9nKHKnZ4XsZZIhdG:lYYTpc44hd2ZicILveIVqdiCjdDCwMlUhfU1iYX\0[ZIhPDhiaILzJIJ6KESDUFmgd5RicW6rbnegZoF{\WRiaX3teY5w\my3b4Lld4NmdmOnIHHzd4F6	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTN3OEG0O{c,Ojl\|NUixOFc9N2F-
TC32	MlnGdWhVWyCjc4PhfS=>				MVjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXEN\|MjDj[Yxtew>?	M{jkdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2	NWK5RlNDeUiWUzDhd5NigQ>?				NWLUbWhPeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=>	M4HRblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	M1z3SJFJXFNiYYPzZZk>				NF;W[JNyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1UUCClZXzsdy=>	NWi5flJCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	M3PRN5FJXFNiYYPzZZk>				NYrU[YVHeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF3HJFY{KCh4LWTHJHIqKGOnbHzz	NInETJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB1643	MWHxTHRUKGG\|c3H5				NWq2d\|h2eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=>	NYnVTGE6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB-EBc1	MYXxTHRUKGG\|c3H5				M4rVNJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJG5DNUWEY{GgZ4VtdHN?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
MG 63 (6-TG R)	M2mxUZFJXFNiYYPzZZk>				MYjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDNS{A3OyBqNj3US{BTMSClZXzsdy=>	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
U-2 OS	M3HXZZFJXFNiYYPzZZk>				NFnXSG1yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBWNTJiT2OgZ4VtdHN?	M4qwRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SJ-GBM2	NX[2fnZ4eUiWUzDhd5NigQ>?				NICwcpJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1qtS2JOOiClZXzsdy=>	NHjucGU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	M3X3dJFJXFNiYYPzZZk>				M2nlWZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz	NULZNoxsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB-EBc1	Mmf0dWhVWyCjc4PhfS=>				NXPrbJJ5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CMWVD[zFiY3XscJM>	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
LAN-5	M4fqU5FJXFNiYYPzZZk>				NW\UN4hleUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh18	MXTxTHRUKGG\|c3H5				NHHiSWhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnixPEBk\Wyucx?=	Ml34QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	MWPxTHRUKGG\|c3H5				NIGydFZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLV3DJINmdGy\|	MlnRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
TC32	NGnBWnpyUFSVIHHzd4F6				MXfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDUR\|MzKGOnbHzz	Mn7EQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Saos-2	M2TuXJFJXFNiYYPzZZk>				M3TDcpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNid3NvMjDj[Yxtew>?	M4TGdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=

... 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 Clin Cancer Res 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 Cell 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 Mol Cells 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 Drug Des Devel Ther 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 FASEB J 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 Oncogene 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 Oncotarget 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 Blood 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]

激酶实验：^[1]	- 合并 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]	- 合并 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-20^oC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]	- 合并 Animal Models: 皮下接种 MM1.S 细胞的SCID鼠 Dosages: ~30 mg/kg/day Administration: 口服处理 (Only for Reference)

参考文献

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	6mg/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 Download Alisertib (MLN8237) SDF

分子量	518.92
化学式	C₂₇H₂₀ClFN₄O₄
CAS号	1028486-01-2
储存条件	3年-20°C 粉状 2年-80°C 溶于溶剂
别名	N/A

动物体内配方计算器 (澄清溶液)

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量

mg/kg

动物平均体重

每只动物给药体积

动物数量

只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO+ % + % Tween 80+ % ddH₂O

计算重置

计算结果:

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH₂O，混匀澄清。

注意：1. 首先保证母液是澄清的；
2. 一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

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、SDS / 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

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、SDS / 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
初始浓度:
稀释倍数:

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

通过输入化合物的化学式来计算其分子量：

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 (data from https://clinicaltrials.gov, updated on 2022-01-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04479306	Recruiting	Drug: Alisertib\|Drug: Osimertinib\|Drug: Sapanisertib	Recurrent Lung Non-Small Cell Carcinoma\|Stage IIIB Lung Cancer AJCC v8\|Stage IV Lung Cancer AJCC v8\|Stage IVA Lung Cancer AJCC v8\|Stage IVB Lung Cancer AJCC v8	M.D. Anderson Cancer Center	June 18 2020	Phase 1
NCT02812056	Withdrawn	Drug: Alisertib\|Drug: TAK-228	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	Completed	Drug: Alisertib\|Drug: MLN0128	Metastatic Breast Cancer\|Solid Tumors	University of Colorado Denver	May 13 2016	Phase 1
NCT02367352	Terminated	Drug: Alisertib\|Drug: Paclitaxel	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。

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.

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.

研究领域

产品类型

定制您的化合物库

Alisertib (MLN8237)

客户使用Selleck生产的Alisertib (MLN8237)发表文献297篇：

产品安全说明书

Aurora Kinase抑制剂选择性比较

生物活性

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)

参考文献

溶解度 (25°C)

化学数据 Download Alisertib (MLN8237) SDF

动物体内配方计算器 (澄清溶液)

计算器

摩尔浓度计算器

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

摩尔浓度计算公式

稀释计算器

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

连续稀释计算器方程

连续稀释

计算结果

分子量计算器

总分子量：g/mol

摩尔浓度计算器

临床试验信息 (data from https://clinicaltrials.gov, updated on 2022-01-17)

技术支持

常见问题及建议解决方法

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

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