Alisertib (MLN8237)

Catalog No.S1133

Molecular Weight(MW): 518.92

Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Phase 3.

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Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Biological Activity

Description

Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Phase 3.

Features

First orally available inhibitor of Aurora A.

Targets

Aurora A ^[1]
(Cell-free assay)

1.2 nM

In vitro

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 Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
HCT116	MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MVmwMlUh\|ryP	M4jPSVczKGh?	Mn3QSG1UVw>?	M1jz[mlEPTB;MD6wOEDPxE1?	MlvCNlYyOzZ4OES=
LS174T	MnHBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MX2wMlUh\|ryP	M3XRN\|czKGh?	MljlSG1UVw>?	NEjlcZlKSzVyPUCuNFUh\|ryP	M3fuOVI3OTN4Nki0
T84	MmfUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MXOwMlUh\|ryP	NGm0PZo4OiCq	Mn61SG1UVw>?	M37BUGlEPTB;MD6wPUDPxE1?	NFr2fnozPjF\|Nk[4OC=>
LS180	M4Xjc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NF:3XG4xNjVizszN	NV:0bHVNPzJiaB?=	MU\EUXNQ	Mn:yTWM2OD1zIN88US=>	M3LCdlI3OTN4Nki0
SW948	NVyxZ2NYT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M{e5NVAvPSEQvF2=	MnXaO\|IhcA>?	M3frdWROW09?	MXXJR\|UxRTFizszN	MYeyOlE{PjZ6NB?=
HCT15	NHLrTWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NXnqVIZFOC53IN88US=>	MVW3NkBp	NXq5e21RTE2VTx?=	MnjxTWM2ODxyLkSg{txO	NG[1cVAzPjF\|Nk[4OC=>
DLD-1	NYTSd2ZGT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MmrkNE42KM7:TR?=	MkTHO\|IhcA>?	MYPEUXNQ	MlLaTWM2ODxyLkig{txO	MYqyOlE{PjZ6NB?=
MIP-101	MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NEjtNIQxNjVizszN	M4PWWFczKGh?	M2XGZWROW09?	MULJR\|UxRTFizszN	MnLSNlYyOzZ4OES=
SNU1544	NF\OTnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MV2wMlUh\|ryP	NW\LSpA5PzJiaB?=	NXPkWpl2TE2VTx?=	MUPJR\|UxRTFizszN	MlezNlYyOzZ4OES=
OCI-Ly10	NVjOWHBvS3m2b4TvfIlkKEG\|c3H5		Mk\tO\|IhcA>?	MXnEUXNQ	MWjJR\|UxRTBwMEW4JO69VQ>?	NFHQe3MzPTh5OEOzNS=>
SU-DHL2	MnzCR5l1d3SxeHnjJGF{e2G7		NX;XfpB3PzJiaB?=	M4qyNGROW09?	MWTJR\|UxRTBwMEGg{txO	NWHNbpoyOjV6N{izN\|E>
OCI-LY7	NYjUNZY5S3m2b4TvfIlkKEG\|c3H5		NHW1XWI4OiCq	M1ezNWROW09?	NUPZfJpLUUN3ME2wMlA5OSEQvF2=	NFXlTFAzPTh5OEOzNS=>
SU-DHL6	MXXDfZRwfG:6aXOgRZN{[Xl?		MUS3NkBp	MV7EUXNQ	NXvuS4o4UUN3ME2wMlQ5OiEQvF2=	MWOyOVg4QDN\|MR?=
Jeko-1	M1zvdGN6fG:2b4jpZ{BCe3OjeR?=		NGi5NY44OiCq	NYHoNo9VTE2VTx?=	NETOPHBKSzVyPUCuNFI6KM7:TR?=	NHLKdZEzPTh5OEOzNS=>
JVM-2	MlLqR5l1d3SxeHnjJGF{e2G7		M{jVTFczKGh?	NIf0T\|NFVVOR	MYHJR\|UxRTBwMEGg{txO	MXqyOVg4QDN\|MR?=
Rec-1	MVnDfZRwfG:6aXOgRZN{[Xl?		MmnWO\|IhcA>?	MXHEUXNQ	NU[1em42UUN3ME2wMlA5PyEQvF2=	NIn6[nozPTh5OEOzNS=>
Z-138	Mn7QR5l1d3SxeHnjJGF{e2G7		NH3pbJQ4OiCq	NEPDN25FVVOR	MVTJR\|UxRTBwMEGzJO69VQ>?	M4PPe\|I2QDd6M{Ox
H9	M1TJeGN6fG:2b4jpZ{BCe3OjeR?=		MYS3NkBp	Mk\USG1UVw>?	NVPNflBlUUN3ME2wMlYh\|ryP	NGfUT\|gzPTh5OEOzNS=>
HH	MoWwR5l1d3SxeHnjJGF{e2G7		MmW0O\|IhcA>?	NILTUYlFVVOR	MkjqTWM2OD1yLkeg{txO	NEXFO3MzPTh5OEOzNS=>
DND41	NEjUdoxEgXSxdH;4bYMhSXO\|YYm=		NIrUdJM4OiCq	M4LVTWROW09?	NVPmTlI4UUN3ME2wMlEh\|ryP	M1z0VFI2QDd6M{Ox
CCL119	NH;YbI1EgXSxdH;4bYMhSXO\|YYm=		NUDiRlJ4PzJiaB?=	MVvEUXNQ	NX3GbWRRUUN3ME2wMlA3OiEQvF2=	MkjBNlU5Pzh\|M{G=
J.Cam 1.6	NH:xN5dEgXSxdH;4bYMhSXO\|YYm=		Mm\QO\|IhcA>?	MmS2SG1UVw>?	NWTnRolbUUN3ME2wMlExPSEQvF2=	M{TZTFI2QDd6M{Ox
Sup-T1	M1HxWGN6fG:2b4jpZ{BCe3OjeR?=		NHq2TVA4OiCq	MU\EUXNQ	MVjJR\|UxRTJwMUSyJO69VQ>?	NGjESZIzPTh5OEOzNS=>
Tib 152	MoPYR5l1d3SxeHnjJGF{e2G7		NHu1eo84OiCq	M36yXmROW09?	MoTFTWM2OD1yLkig{txO	M4fFRlI2QDd6M{Ox
MCF7	NWmwUGZ4TnWwY4Tpc44hSXO\|YYm=	M1vFWlUh\|ryP	MnuxNlQhcA>?	MXXEUXNQ	MoTmTY5lfWOnczDHNk9OKGG{cnXzeC=>	NGjDT40zPTh\|NESwNS=>
MDA-MB-231	MV7GeY5kfGmxbjDBd5NigQ>?	MW[1JO69VQ>?	NW\FUplmOjRiaB?=	NYL0OZM2TE2VTx?=	NFKxRpNKdmS3Y3XzJGc{N01iYYLy[ZN1	Mo\LNlU5OzR2MEG=
MCF7	MonwSpVv[3Srb36gRZN{[Xl?	MnPlOUDPxE1?	NF\WZpEzPCCq	M2\JcGROW09?	MYjE[YNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNU9ETEN{	Mn\tNlU5OzR2MEG=
MCF7	MmHESpVv[3Srb36gRZN{[Xl?	Mnj1OUDPxE1?	MV6yOEBp	M2fPfmROW09?	NGrlbZlF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOg>?	M4PTeVI2QDN2NECx
MCF7	MmOzSpVv[3Srb36gRZN{[Xl?	MWe1JO69VQ>?	MmnmNlQhcA>?	NWTjZVdTTE2VTx?=	NWTrTJlbTGWlcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJIN6[2yrbjDCNS=>	NF6yWXozPTh\|NESwNS=>
MCF7	NV;5V3k2TnWwY4Tpc44hSXO\|YYm=	NHTG[Ic2KM7:TR?=	MXmyOEBp	MXXEUXNQ	NUHRTYJjUW6lcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJJAzOSCZYX[xM2NqeDF?	MWGyOVg{PDRyMR?=
MCF7	NEfuPIRHfW6ldHnvckBCe3OjeR?=	MlTQOUDPxE1?	M3XVOVI1KGh?	M1m3cWROW09?	MYjJcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF?	Mn2xNlU5OzR2MEG=
MDA-MB-231	NHW3XI1HfW6ldHnvckBCe3OjeR?=	NHzrUFg2KM7:TR?=	M2i0ZVI1KGh?	MYHEUXNQ	NGKxUZZF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOS:FRFOy	M{mye\|I2QDN2NECx
MDA-MB-231	NXHiWYE{TnWwY4Tpc44hSXO\|YYm=	NYq4VoU2OSEQvF2=	M33IelI1KGh?	MkjUSG1UVw>?	M1i2SGlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz	M1GyZlI2QDN2NECx
MDA-MB-231	NXLSRVBITnWwY4Tpc44hSXO\|YYm=	MWe1JO69VQ>?	M2H6[VI1KGh?	M2DnZmROW09?	NYf6cHZ[TGWlcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJIN6[2yrbjDCNS=>	M2O4UlI2QDN2NECx
MDA-MB-231	NGTFdXlHfW6ldHnvckBCe3OjeR?=	M4\mfFUh\|ryP	NG\kR3kzPCCq	NEm3PXdFVVOR	NWW0XoZKUW6lcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJJAzOSCZYX[xM2NqeDF?	NVzDdJFbOjV6M{S0NFE>
MDA-MB-231	MnTGSpVv[3Srb36gRZN{[Xl?	MlnQOUDPxE1?	NXXqdno1OjRiaB?=	MYrEUXNQ	Ml;hTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyO{BMcXBz	NGLWO5IzPTh\|NESwNS=>
MDA-MB-231	NWjJNnpRTnWwY4Tpc44hSXO\|YYm=	M4ruO\|Uh\|ryP	NF3uVZozPCCq	MnLaSG1UVw>?	MoTQTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIIC1Ny=>	NYj0U4hzOjV6M{S0NFE>
MCF7	MnP4RZBweHSxc3nzJGF{e2G7	M1L2bFUh\|ryP	M1zBfFI1KGh?	MmTOSG1UVw>?	NUfNbpNJUW6mdXPld{BieG:ydH;0bYMh\GWjdHi=	M1vJUFI2QDN2NECx
MDA-MB-231	NUi5PJB4SXCxcITvd4l{KEG\|c3H5	MWK1JO69VQ>?	M4DnZVI1KGh?	MX\EUXNQ	NXHkTIJwUW6mdXPld{BieG:ydH;0bYMh\GWjdHi=	MUCyOVg{PDRyMR?=
MCF7	M2j3b2Z2dmO2aX;uJGF{e2G7	NGHPd5gyKM7:TR?=	NYT0OpdUPzJiaB?=	NGXDS2FFVVOR	MoizTY5lfWOnczDheZRweGijZ3njJIRm[XSq	M3XlNFI2QDN2NECx
MDA-MB-231	M1jST2Z2dmO2aX;uJGF{e2G7	NFfI[4wyKM7:TR?=	NGDmZYg4OiCq	MlzqSG1UVw>?	NW\pSW9kUW6mdXPld{BifXSxcHjh[4lkKGSnYYTo	M{nURlI2QDN2NECx
U-2 OS	MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MUi1NEDPxE1?	MkjGNlQhcA>?	NIr6TINFVVOR	MX;JR\|UxRTF4Lk[g{txO	Ml\TNlU4QTJ6MUG=
MG-63	NVi5OIlZT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MlS2OVAh\|ryP	M2rFeVI1KGh?	MX\EUXNQ	MYLJR\|UxRTlwNTFOwG0>	MnjvNlU4QTJ6MUG=
U-2 OS	MXvBdI9xfG:\|aYOgRZN{[Xl?	MYW1JO69VQ>?	NXnJW4JUOjRiaB?=	MXTEUXNQ	NEjwVGJKdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRp	NGe2W2wzPTd7MkixNS=>
MG-63	MXnBdI9xfG:\|aYOgRZN{[Xl?	MVm1JO69VQ>?	NFfsfVUzPCCq	NWm2NHc2TE2VTx?=	NWjKZXBwUW6mdXPld{BieG:ydH;0bYMh[2WubDDk[YF1cA>?	MnTINlU4QTJ6MUG=
U-2 OS	MVrGeY5kfGmxbjDBd5NigQ>?	MnzaOUDPxE1?	MWKyOEBp	MX7EUXNQ	M2nYRXBzd22xdHXzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>?	M4PoXVI2Pzl{OEGx
MG-63	M4PHR2Z2dmO2aX;uJGF{e2G7	Mke2OUDPxE1?	NUH3PFlmOjRiaB?=	NVW0e\|ZDTE2VTx?=	M3;pbnBzd22xdHXzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>?	MYOyOVc6OjhzMR?=
PANC-1	MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MX61NEDPxE1?	M4jJb\|I1KGh?	MUHEUXNQ	NHfMWXNKSzVyPUeuNUDPxE1?	NULCfnYxOjV4M{KyNlU>
BxPC-3	NYjxRldVT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NXnrVZBFPTBizszN	NX;rfoJxOjRiaB?=	M3zqcGROW09?	MUnJR\|UxRTZwODFOwG0>	NIDtWpozPTZ\|MkKyOS=>
PANC-1	MYDGeY5kfGmxbjDBd5NigQ>?	NH;IV4w2KM7:TR?=	MknBNlQhcA>?	MYjEUXNQ	MnjCTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dDDpckBIOi:PIIDoZZNm	M1WxTlI2PjN{MkK1
BxPC-3	NUi5NWJRTnWwY4Tpc44hSXO\|YYm=	MkixOUDPxE1?	M{DkT\|I1KGh?	MVLEUXNQ	MYDJcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2IHnuJGczN01icHjhd4U>	M3WxdlI2PjN{MkK1
PANC-1	NWjQTnl4TnWwY4Tpc44hSXO\|YYm=	NFrMPGY2KM7:TR?=	M1T4flI1KGh?	NUnaZoVqTE2VTx?=	NV6zeXlQUW6mdXPld{BifXSxcHjh[4lkKGOnbHyg[IVifGh?	MmSxNlU3OzJ{MkW=
BxPC-3	M3fOPGZ2dmO2aX;uJGF{e2G7	NWPLOpVtPSEQvF2=	MYCyOEBp	M2G4SmROW09?	NHHKZYxKdmS3Y3XzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>?	NYH2[INHOjV4M{KyNlU>
SKOV3	M3\1N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MUWxNFAh\|ryP	MUeyOEBp	NUW4SXk5TE2VTx?=	NH;iTXlKSzVyPUKwMlQ5KM7:TR?=	MlfDNlU3OjR5NUC=
OVCAR4	NE\J[YtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MX6xNFAh\|ryP	M2PJelI1KGh?	MWrEUXNQ	NYj5UG5MUUN3ME2yNk4yOyEQvF2=	NVywVph6OjV4MkS3OVA>
SKOV3	NVHK[GhJTnWwY4Tpc44hSXO\|YYm=	M3\3UFUh\|ryP	MkXmO\|IhcA>?	M1TRfGROW09?	NETYc49KdmS3Y3XzJGczN01iYYLy[ZN1	NYO0TmdCOjV4MkS3OVA>
OVCAR4	M1fYb2Z2dmO2aX;uJGF{e2G7	NYrBZlJQPSEQvF2=	MoHtO\|IhcA>?	NVPJelZNTE2VTx?=	M3T1bWlv\HWlZYOgS\|IwVSCjcoLld5Q>	M2\BN\|I2PjJ2N{Ww
SKOV3	MUHBdI9xfG:\|aYOgRZN{[Xl?	NY\HTWhRPSEQvF2=	NGDjfFkzPCCq	M37sOmROW09?	M3fQS2lv\HWlZYOgZZBweHSxc3nz	NELTeoQzPTZ{NEe1NC=>
OVCAR4	NVjJeXZMSXCxcITvd4l{KEG\|c3H5	M{XHWVUh\|ryP	NXrTe4k4OjRiaB?=	NYqybFhiTE2VTx?=	MX;JcoR2[2W\|IHHwc5B1d3Orcx?=	NVO2RmM6OjV4MkS3OVA>
AGS	NUHFVFJ1T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	Ml:5NlUh\|ryP	MXqyOEBp	MkHJSG1UVw>?	MYLJR\|UxRTF7LkC5JO69VQ>?	MX[yOVYxQTl{Mx?=
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NCI-N78	MULBdI9xfG:\|aYOgRZN{[Xl?	NYf0SmdNPSEQvF2=	MlywNlQhcA>?	M3LC[mROW09?	M1S2emlv\HWlZYOgZZBweHSxc3nz	M4fEeVI2PjB7OUKz
AGS	NW\0W21TTnWwY4Tpc44hSXO\|YYm=	NWjDTmdkPSEQvF2=	MojnNlQhcA>?	NYHxVVF7TE2VTx?=	MUjJcoR2[2W\|IITo[UBifXSxcHjh[5k>	NI\BW5UzPTZyOUmyNy=>
NCI-N78	M1\3OWZ2dmO2aX;uJGF{e2G7	NUnOUmxTPSEQvF2=	Ml:4NlQhcA>?	M{noR2ROW09?	NWTibXhqUW6mdXPld{B1cGViYYX0c5Bp[We7	NFnvOJgzPTZyOUmyNy=>
HSC-3	MnTMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NXH0VJB{OSEQvF2=	NWTjeWtKPDhiaB?=		NILofmNKSzVyPUCuOVQh\|ryP	M4\rdlI2OzZ4MUSz
GB30	NULGZmh3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MUixJO69VQ>?	MYi3JIQ>	NVXudGpETE2VTx?=	MWPJR\|UxRTBwMEGxJO69VQ>?	Mo\GNlUyODZ2Mki=
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GB169	NFf1S3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NFj1blEyKM7:TR?=	MkLHO{Bl	MkDiSG1UVw>?	M2HGfmlEPTB;MD6wN\|Ih\|ryP	MWmyOVExPjR{OB?=
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UM-UC-3	NVjFO4RWTnWwY4Tpc44hSXO\|YYm=	NH3rbZkyKM7:TR?=	MYC0PEBp	NWTzZnFlTE2VTx?=	NHvKU2pKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	MVuyN\|QxOzZ\|Mx?=
T24	NGDPcVZCeG:ydH;zbZMhSXO\|YYm=	NHS4RpM{NjF4IN88US=>	Mn[3PVYhcA>?	NVjRTZdOTE2VTx?=	M1rOT2lEPTB;MD6wN\|A3KM7:TR?=	M1LaPVI{PDB\|NkOz
RT4	NHTic21CeG:ydH;zbZMhSXO\|YYm=	NX\KXVc1Oy5zNjFOwG0>	Mn7xPVYhcA>?	NEHFN\|RFVVOR	M1i5NWlEPTB;MD6xNVk5KM7:TR?=	MmP2NlM1ODN4M{O=
UM-UC-3	NFLWWWZCeG:ydH;zbZMhSXO\|YYm=	MUWzMlE3KM7:TR?=	M{T6eFk3KGh?	MoG2SG1UVw>?	MlfOTWM2OD1yLkC0OFkh\|ryP	NYXqU5dJOjN2MEO2N\|M>
OVCAR-5	NHH3PVBHfW6ldHnvckBCe3OjeR?=	MmnuOVAhdk1?			NVnSNoZPUW6qaXLpeJMh[2WubDDtbYdz[XSrb36=	MUSyN\|M{PDN{Nx?=
SKOV3ip2	NYTJUnR7TnWwY4Tpc44hSXO\|YYm=	NYSxU4VQPTBibl2=			MVPJcohq[mm2czDj[YxtKG2rZ4LheIlwdg>?	NXX0ToZmOjN\|M{SzNlc>
S462	MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NHe4WFAyODBizszN	Mmq4O\|IhcA>?	MUDEUXNQ	NEXWV3ZCfHSnboXheIV{KGOnbHyg[5Jwf3Sq	MVGyN\|MzQDFzNB?=
2884	NHnhfpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MXWxNFAh\|ryP	MXW3NkBp	M2Pue2ROW09?	NXvRU2w6SXS2ZX71ZZRmeyClZXzsJIdzd3e2aB?=	NFHsWIozOzN{OEGxOC=>
2885	M1XNfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NULrZ5ZwOTByIN88US=>	NVvEVZlyPzJiaB?=	NXLxbZBnTE2VTx?=	NULY[5hKSXS2ZX71ZZRmeyClZXzsJIdzd3e2aB?=	NIP4W48zOzN{OEGxOC=>
CRL-2396	MnftS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NV3vfmdUOTByIN88US=>		M2T0UpdifGW{	M4TvVGlEPTB;MD6wPVIh\|ryP	M4e1d\|I{OTV\|NUK0
TIB-48	MlHiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NHfROVUyODBizszN		M1nl[JdifGW{	NFXqflFKSzVyPUCuNFg5KM7:TR?=	NIjsXJYzOzF3M{WyOC=>
CRL-2396	MYjDfZRwfG:6aXOgRZN{[Xl?	M{fxVlEh\|ryP	M2rpOFQ5KGh?	MmDve4F1\XJ?	MX;JcoR2[2W\|IHHwc5B1d3Orcx?=	NXHDXItNOjNzNUO1NlQ>
TIB-48	MXLDfZRwfG:6aXOgRZN{[Xl?	NHjVbmIyKM7:TR?=	MUG0PEBp	MmTEe4F1\XJ?	NIrHZVdKdmS3Y3XzJIFxd3C2b4Ppdy=>	NVHjbmlmOjNzNUO1NlQ>
AGS	NUf6fYt6S3m2b4TvfIlkKEG\|c3H5	NX\Hc2hNOC53IN88US=>	NHTBfFUzPCCq	NIHOZVJFVVOR	NXjOS481TGWlcnXhd4V{KGOnbHygd5Vzfmm4YXy=	MlHNNlI6PzJ4MUG=
FLO-1	MljaR5l1d3SxeHnjJGF{e2G7	NG\JSHUxNjVizszN	NWfycFN5OjRiaB?=	MUjEUXNQ	M4q0WWRm[3KnYYPld{Bk\WyuIIP1dpZqfmGu	M1XzUVIzQTd{NkGx
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SKLMS	MX\DfZRwfG:6aXOgRZN{[Xl?	M{LxZlc2KG6P	M1\CWFk3KGh?		NVvXVVNjUW6mdXPld{BieG:ydH;zbZM>	NFfD[IkzOjh{MUm5Oy=>
Leio285	M1vSeWN6fG:2b4jpZ{BCe3OjeR?=	MUC3OUBvVQ>?	NUnQcIx4QTZiaB?=		M4G1Wmlv\HWlZYOgZZBweHSxc3nz	MkDrNlI5OjF7OUe=
Mes-Sa	NIP5NppEgXSxdH;4bYMhSXO\|YYm=	MlPzO\|Uhdk1?	Mlu4PVYhcA>?		MU\JcoR2[2W\|IHHwc5B1d3Orcx?=	M1LnfVIzQDJzOUm3
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Molt-4	MkPSR5l1d3SxeHnjJGF{e2G7	MkHDNVAh\|ryP	NEDSdoo4OiCq	MUPEUXNQ	NFrPTINKSzVyPUCuNFIh\|ryP	Moq1NlI3Pjl\|M{W=
MOLM-13	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M{PGfVMh\|ryP	MoLSO\|IhcA>?		M4G2VGRqdWmwaYPo[ZMh[2WubDD2bYFjcWyrdIm=	MmS4NlI1QDh{NEm=
HL-60	MnjxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGrE[4g{KM7:TR?=	NHPOeFM4OiCq		NEf6TpNFcW2rbnnzbIV{KGOnbHygeoli[mmuaYT5	NED1S4gzOjR6OEK0PS=>
MV4-11	M4LOU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NHS5Tok{KM7:TR?=	M2D5blczKGh?		MV;EbY1qdmm\|aHXzJINmdGxidnnhZoltcXS7	NVPST49qOjJ2OEiyOFk>
SKM-1	Mlu5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	Ml;CN{DPxE1?	NIrsPWo4OiCq		M{PRVWRqdWmwaYPo[ZMh[2WubDD2bYFjcWyrdIm=	NHvrcmUzOjR6OEK0PS=>
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NOMO-1	NILnZVJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NWPXNZhGOyEQvF2=	MXq3NkBp		NFiz[HBFcW2rbnnzbIV{KGOnbHygeoli[mmuaYT5	NHjIUlczOjR6OEK0PS=>
OCL-AML2	M{jIXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M1X3[FMh\|ryP	MkfXO\|IhcA>?		NVrsVHJTTGmvaX7pd4hmeyClZXzsJJZq[WKrbHn0fS=>	NWjsTnFHOjJ2OEiyOFk>
PL-21	MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M1zmNlMh\|ryP	MX63NkBp		NVn5SWV7TGmvaX7pd4hmeyClZXzsJJZq[WKrbHn0fS=>	NEXhdoszOjR6OEK0PS=>
KG-1	NXTNe4cyT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M3fRS\|Mh\|ryP	MlWyO\|IhcA>?		MmrWSIlucW6rc3jld{Bk\WyuII\pZYJqdGm2eR?=	NFnnbWczOjR6OEK0PS=>
A172	MkPBR5l1d3SxeHnjJGF{e2G7	MkfhNVAxKM7:TR?=	NY[zOlVbOjRiaB?=	MWrEUXNQ	M3zBSmlEPTB;MD6xNlAh\|ryP	NXeyeogxOjJ{N{SzPVk>
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U251	M{ToVGN6fG:2b4jpZ{BCe3OjeR?=	MkPHNVAxKM7:TR?=	NH74SIQzPCCq	NHrHTolFVVOR	M1j4[2lEPTB;MD6xNFAh\|ryP	MmrYNlIzPzR\|OUm=
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LN18	NFzIWJZEgXSxdH;4bYMhSXO\|YYm=	MUmxNFAh\|ryP	MVuyOEBp	MVHEUXNQ	MoLmTWM2OD1yLkKxNEDPxE1?	M4XtXVIzOjd2M{m5
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HF66	NYPqUo54S3m2b4TvfIlkKEG\|c3H5	NFfmfWYyODBizszN	NVf1UXdNOjRiaB?=	MnjsSG1UVw>?	NGDmWZNKSzVyPUCuNlI2KM7:TR?=	NYm1[2NyOjJ{N{SzPVk>
HF2303	NEmyRXhEgXSxdH;4bYMhSXO\|YYm=	NXPrO4puOTByIN88US=>	M{DrcVI1KGh?	Mk\XSG1UVw>?	MYfJR\|UxRTBwME[wJO69VQ>?	MWCyNlI4PDN7OR?=
HF2359	NYjqZnJvS3m2b4TvfIlkKEG\|c3H5	M{DpSVExOCEQvF2=	MV:yOEBp	NEjuVZRFVVOR	NVzoVoZiUUN3ME2wMlA3OCEQvF2=	NWLmNnBWOjJ{N{SzPVk>
HF2414	Mm[0R5l1d3SxeHnjJGF{e2G7	Mn:xNVAxKM7:TR?=	M2X4ZVI1KGh?	M2LB[GROW09?	MmfRTWM2OD1yLkC4NEDPxE1?	MY[yNlI4PDN7OR?=
A-673	NVq2NW9MT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M2D4TlExKM7:TR?=	M2DidFk3KGh?	MVvEUXNQ	MWTJR\|UxRTBwMEOyJO69VQ>?	MmXTNlE1PDh3OUG=
TC-32	M1HNNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NXLUTGpZOTBizszN	NI\COFU6PiCq	NF7ZNoVFVVOR	NWHLPWxnUUN3ME2wMlA{QSEQvF2=	NYfObYgxOjF2NEi1PVE>
TC-71	NYnOVnpyT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MUKxNEDPxE1?	NFPEZ4Y6PiCq	M{DkTmROW09?	NYjIO\|VUUUN3ME2wMlExOiEQvF2=	MXOyNVQ1QDV7MR?=
SK-N-MC	NWHTNIF2T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MljyNVAh\|ryP	NGnJ[3Q6PiCq	MVLEUXNQ	M1zMSWlEPTB;MD6wO\|Ih\|ryP	NX[wd5VnOjF2NEi1PVE>
CHLA-9	MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Mlj6NVAh\|ryP	MmLhPVYhcA>?	MlPDSG1UVw>?	M2ezdGlEPTB;MD6wNVgh\|ryP	M{XQXlIyPDR6NUmx
CHLA-10	M{fEN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MmT2NVAh\|ryP	Ml73PVYhcA>?	M13nNmROW09?	Mo\wTWM2OD1yLkC2NEDPxE1?	NV\tZmlvOjF2NEi1PVE>
CHLA-25	MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NHPvdXQyOCEQvF2=	MWW5OkBp	MWjEUXNQ	Ml3OTWM2OD1yLkG2PEDPxE1?	M{HKfVIyPDR6NUmx
CHLA-32	NE\rZ\|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MVyxNEDPxE1?	NX6zUVBKQTZiaB?=	NIrrVIlFVVOR	Mn\LTWM2OD1yLkGzOkDPxE1?	MWqyNVQ1QDV7MR?=
CHLA-56	MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M{fhfVExKM7:TR?=	NH7NZ5c6PiCq	NWjkXGlXTE2VTx?=	NU[5[ZRSUUN3ME2xNEDPxE1?	NWHUPG93OjF2NEi1PVE>
CHLA-258	MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NG\Cd\|AyOCEQvF2=	MlixPVYhcA>?	MlvOSG1UVw>?	MVfJR\|UxRTBwMUOyJO69VQ>?	NV62UWdsOjF2NEi1PVE>
COG-E-352	M{fMfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MVOxNEDPxE1?	M1LIXVk3KGh?	MlfISG1UVw>?	M4rzRmlEPTB;MD6wOFMh\|ryP	NGXnXWkzOTR2OEW5NS=>
CHLA-90	MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NIX4O\|UyOCEQvF2=	M2DMWlk3KGh?	NX\RN3Y5TE2VTx?=	M{jNTWlEPTB;MD6wOlEh\|ryP	MkP1NlE1PDh3OUG=
CHLA-119	MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NYnIc2VyOTBizszN	M3q1Wlk3KGh?	MkLtSG1UVw>?	M3H2[2lEPTB;MD6wNlIh\|ryP	MVKyNVQ1QDV7MR?=
CHLA-122	MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NUfmPVdkOTBizszN	NXP4N5ZtQTZiaB?=	MW\EUXNQ	MUHJR\|UxRTBwMEG5JO69VQ>?	Mke4NlE1PDh3OUG=
CHLA-136	MnPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MXyxNEDPxE1?	NEjiepA6PiCq	MYTEUXNQ	MXLJR\|UxRTBwMEO5JO69VQ>?	NWXqVmFOOjF2NEi1PVE>
CHLA-140	MkGzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NHe2OI8yOCEQvF2=	MmPyPVYhcA>?	MWfEUXNQ	NH\4XYhKSzVyPUCuNFI3KM7:TR?=	NUnPcldpOjF2NEi1PVE>
LA-N-6	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4\YOFExKM7:TR?=	NVzxbVZlQTZiaB?=	M3jDVGROW09?	NWiwS\|FJUUN3ME2wMlA2PCEQvF2=	MoTENlE1PDh3OUG=
NB-1643	MoXjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NIPvOIUyOCEQvF2=	MojXPVYhcA>?	NX7D[2lnTE2VTx?=	NX\SW3RHUUN3ME2wMlA{PyEQvF2=	M1rSTVIyPDR6NUmx
NB-EBc1	MluzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MV[xNEDPxE1?	M1TsRlk3KGh?	NF:1SGxFVVOR	M2DHWmlEPTB;MD6wOVAh\|ryP	MXuyNVQ1QDV7MR?=
SK-N-BE-1	MoXhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NF\UPVgyOCEQvF2=	NVTPbpZNQTZiaB?=	MlnmSG1UVw>?	Mo\STWM2OD1yLkCyPEDPxE1?	M3vlTlIyPDR6NUmx
SK-N-BE-2	NFjuR4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NUjzU\|JFOTBizszN	NV:3T4RiQTZiaB?=	NGf6c5RFVVOR	M4LKVmlEPTB;MD6wN\|Yh\|ryP	MV:yNVQ1QDV7MR?=
SMS-KAN	MkTTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MkPzNVAh\|ryP	NGnBenM6PiCq	NFTWT3RFVVOR	MlXMTWM2OD1yLkCzOEDPxE1?	NHHLV2ozOTR2OEW5NS=>
SMS-KANR	M3jBZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3;nN\|ExKM7:TR?=	M2TyO\|k3KGh?	M{\TVGROW09?	NUnWdohkUUN3ME2wMlAzPiEQvF2=	NWnUTZVFOjF2NEi1PVE>
SMS-KCN	Mk[yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MV:xNEDPxE1?	NV;LTWFxQTZiaB?=	M3XNeGROW09?	MVHJR\|UxRTBwMEG5JO69VQ>?	NX\kZWNMOjF2NEi1PVE>
SMS-KCNR	M2fCfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NXG5fGxYOTBizszN	MlLMPVYhcA>?	NX\zSZNQTE2VTx?=	NVq3RVl[UUN3ME2wMlAyOCEQvF2=	NIrP[JMzOTR2OEW5NS=>
SMS-LHN	NEn3cXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYqxNEDPxE1?	NXu2TnpsQTZiaB?=	MWfEUXNQ	NGH3[XpKSzVyPUCuNFMzKM7:TR?=	NXvqeJlIOjF2NEi1PVE>
SMS-MSN	NUTVUXVDT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NGXpVZIyOCEQvF2=	NFT1cZc6PiCq	NYC3NHB6TE2VTx?=	MmTvTWM2OD1yLkCyNkDPxE1?	NWXUV2VZOjF2NEi1PVE>
SMS-SAN	MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4L0UVExKM7:TR?=	M2DXd\|k3KGh?	NYDLfW1qTE2VTx?=	NFrjXoNKSzVyPUCuNFIxKM7:TR?=	MnzSNlE1PDh3OUG=
Granta-4	M1jMXmN6fG:2b4jpZ{BCe3OjeR?=	NGLM[GoyOCEQvF2=	NFr6[Vk4KGR?		M3GzNWlEPTB;MD6wOFAh\|ryP	NWPDcoZROjF{OUG4Olc>
DB	NVWwOJNLS3m2b4TvfIlkKEG\|c3H5	M{D2UFExKM7:TR?=	NFGwd4Y4KGR?		NVLlfo1lUUN3ME2wMlA1OiEQvF2=	NXvYe2xkOjF{OUG4Olc>
RL	NGTxV2lEgXSxdH;4bYMhSXO\|YYm=	NWm3WWFSOTBizszN	MUW3JIQ>		M2PIZ2lEPTB;MD6wNVUh\|ryP	NFj2XHEzOTJ7MUi2Oy=>
K562	M4jXemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3HnRlExKM7:TR?=	NXXjZ5lUQTZiaB?=		NGLtbFNKSzVyPUCuNFg4KM7:TR?=	NXXCXGk3OjFyOUG2N\|M>
LAMA-84	MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NYfGbYtDOTBizszN	MkLjPVYhcA>?		M2fUeWlEPTB;MD6wOVch\|ryP	NX7qeXhFOjFyOUG2N\|M>
MM15	NXLKdWlMT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NInDdWU1KM7:TR?=	MX[3NkBp	NH\PdXpFVVOR	NYLC[Ys5UUN3ME2wMlE{KM7:TR?=	MojONlA{QDJ6NES=
OPM1	Mnr1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NV62NlROPCEQvF2=	NXnZeFdkPzJiaB?=	NXTDbHdFTE2VTx?=	M1uwd2lEPTB;MD6wN{DPxE1?	MUGyNFM5Ojh2NB?=
RPM1	NFnwcVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NGnaTFQ1KM7:TR?=	MWK3NkBp	NVrnOZJVTE2VTx?=	NYrxNFFPUUN3ME2xNE4{OiEQvF2=	NGnp[nUzODN6Mki0OC=>
INA6	MlvlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MUK0JO69VQ>?	NWfqc5JRPzJiaB?=	NVz0e5JmTE2VTx?=	NELqTmtKSzVyPUCuNFAzKM7:TR?=	M1jPc\|IxOzh{OES0
OPM2	NHP2O49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M1fZWFQh\|ryP	NXqye5Z4PzJiaB?=	NU[xN5dvTE2VTx?=	M{DocWlEPTB;ND6zO{DPxE1?	MmiyNlA{QDJ6NES=
MM1R	NYrx[pR[T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MVq0JO69VQ>?	NV\ufJR3PzJiaB?=	NWPxdIt2TE2VTx?=	NXS3ZZc3UUN3ME2xMlY5KM7:TR?=	MUKyNFM5Ojh2NB?=
DOX40	MmrDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MojVOEDPxE1?	M1vxRVczKGh?	M3m1eWROW09?	M33IU2lEPTB;NT60PEDPxE1?	MX[yNFM5Ojh2NB?=
LR5	MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NGnMNXc1KM7:TR?=	MYm3NkBp	NFjsSJpFVVOR	NGHUXldKSzVyPUKuOVMh\|ryP	MlnhNlA{QDJ6NES=
U266	NWXLclc{T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MnrxOEDPxE1?	M4\UblczKGh?	NUe0e2V[TE2VTx?=	NVTOOIsyUUN3ME2xMlQ{KM7:TR?=	NVzDdmFjOjB\|OEK4OFQ>
RD	MoDwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NWXt[HFwOTBizszN	MYS5OkBp		NY[1dWV7UUN3ME2wMlIzQCEQvF2=	MUWyNFExQDN\|OB?=
Rh41	M{TXdmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M1P3c\|ExKM7:TR?=	MXi5OkBp		M2\6VWlEPTB;MD6wPVAh\|ryP	NHPxSG4zODFyOEOzPC=>
Rh30	MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NXH2NGl4OTBizszN	NHTYZ2M6PiCq		NG\2c3hKSzVyPUCuNlMxKM7:TR?=	MmHLNlAyODh\|M{i=
BT-12	NXzSXI84T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NWjrZlF5OTBizszN	NV60S4FqQTZiaB?=		M3zmV2lEPTB;MD6wOlAh\|ryP	MU[yNFExQDN\|OB?=
CHLA-266	MkfKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M{DhelExKM7:TR?=	NV\rVVNkQTZiaB?=		M3\UfGlEPTB;MD6wO\|Ih\|ryP	MkfDNlAyODh\|M{i=
TC-71	NEjkUY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NFPJcJYyOCEQvF2=	MU[5OkBp		M1m5ZmlEPTB;MD6xNFIh\|ryP	MoXSNlAyODh\|M{i=
SJ-GBM2	MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M{DobVExKM7:TR?=	MXG5OkBp		M4nGZmlEPTB;MD6wOVAh\|ryP	MmrxNlAyODh\|M{i=
NALM-6	NUTSNVVGT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NHnaTYsyOCEQvF2=	MUS5OkBp		NYLjTYNqUUN3ME2wMlA3OiEQvF2=	NVK3Xm81OjBzMEizN\|g>
COG-LL-317	NHP3eGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MkTHNVAh\|ryP	MoTDPVYhcA>?		M{Wze2lEPTB;MD6wOFch\|ryP	MofmNlAyODh\|M{i=
RS4-11	NVjMfGRIT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M1LjelExKM7:TR?=	NGWyR3c6PiCq		M2noPWlEPTB;MD6wNVgh\|ryP	M2fie\|IxOTB6M{O4
MOLT-4	MlfZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NELHd\|MyOCEQvF2=	MWe5OkBp		NX3scHd[UUN3ME2wMlAzPiEQvF2=	M1rGd\|IxOTB6M{O4
CCRF-CEM	MlnZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MXSxNEDPxE1?	NHr5R286PiCq		NH\4c45KSzVyPUCuNFk1KM7:TR?=	MnPINlAyODh\|M{i=
Kasumi-1	NUO3fI5FT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NGLMNlcyOCEQvF2=	MVK5OkBp		MnnRTWM2OD1yLkGwN{DPxE1?	M4rKU\|IxOTB6M{O4
Karpas-299	NUD5RVlVT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NX\ad4JoOTBizszN	NGHQUng6PiCq		NYT5em1lUUN3ME2wMlA{QCEQvF2=	NEe4UmgzODFyOEOzPC=>
Ramos-RA1	MofoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NX7aWoRrOTBizszN	M4nkeVk3KGh?		NG[wSGVKSzVyPUCuNVI4KM7:TR?=	NH:wZWEzODFyOEOzPC=>

... 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

In vivo

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]

Protocol

Kinase Assay:^[1]	+ Expand 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.
Cell Research:^[2]	+ Expand Cell lines: MM1.S, MM.1R, LR5, RPMI 8226, DOX40, OPM1, OPM2, INA6, and U266 Concentrations: Dissolved in DMSO, final concentrations ~10 μM Incubation Time: 24, 48, and 72 hours Method: 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. (Only for Reference)
Animal Research:^[2]	+ Expand Animal Models: Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells Formulation: Formulated in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate Dosages: ~30 mg/kg/day Administration: Orally (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	27 mg/mL (52.03 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5%DMSO+30% PEG300+5%Tween-80+ddH2O For best results, use promptly after mixing.	8mg/mL

* 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.

Chemical Information Download Alisertib (MLN8237) SDF

Molecular Weight	518.92
Formula	C₂₇H₂₀ClFN₄O₄
CAS No.	1028486-01-2
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-10-14)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
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	Recruiting	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

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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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.

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

Pan Aurora Kinase Inhibitor

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

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

MK-5108 (VX-689) : Aurora A, IC50=0.064 nM.
Aurora Kinase Inhibitor in Clinical Trial

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

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

Related Aurora Kinase Products

Ro-3306 ^New

RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with K_i of 20 nM, >15-fold selectivity against a diverse panel of human kinases.
CCG-1423 ^New

CCG-1423 is a specific RhoA pathway inhibitor, which inhibits SRF-mediated transcription.
ML141 ^New

ML141 (CID-2950007), is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with IC50 of 200 nM and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7).
Barasertib (AZD1152-HQPA|AZD2811)

Barasertib (AZD1152-HQPA) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1.
Tozasertib (VX-680, MK-0457)

Tozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with K_i_app of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. Phase 2.
Danusertib (PHA-739358)

Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Phase 2.
ZM 447439

ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.

Features:An Aurora selective ATP-competitive inhibitor.
MLN8054

MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM in Sf9 insect cell. It is more than 40-fold selective for Aurora A than Aurora B. Phase 1.
MK-5108 (VX-689)

MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. Phase 1.
Aurora A Inhibitor I (TC-S 7010)

Aurora A Inhibitor I is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM in a cell-free assay. It is 1000-fold more selective for Aurora A than Aurora B.

Features:Aurora A Inhibitor I is a novel, potent, and selective inhibitor to Aurora A.

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Alisertib (MLN8237)

Cited by 79 Publications

Purity & Quality Control

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Biological Activity

Protocol

References

Solubility (25°C)

Chemical Information Download Alisertib (MLN8237) SDF

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Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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Total Molecular Weight: g/mol

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-10-14)

Tech Support

Frequently Asked Questions

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

Related Aurora Kinase Products

Choose Your Country or Region

By Signaling Pathways

By product type

Alisertib (MLN8237)

Cited by 79 Publications

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Biological Activity

Protocol

References

Solubility (25°C)

Chemical Information Download Alisertib (MLN8237) SDF

Bio Calculators

Molarity Calculator

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

Dilution Calculator

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

The Serial Dilution Calculator Equation

Serial Dilutions

Computed Result

Molecular Weight Calculator

Total Molecular Weight: g/mol

Instructions to calculate molar mass (molecular weight) of a chemical compound:

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-10-14)

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Frequently Asked Questions

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

Related Aurora Kinase Products

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)