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Alisertib (MLN8237)

Name: Alisertib (MLN8237)
Brand: Selleck Chemicals
SKU: S1133
Rating: 5 (305 reviews)

Catalog No.S1133

For research use only.

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. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.

CAS No. 1028486-01-2

Selleck's Alisertib (MLN8237) has been cited by 305 publications

Purity & Quality Control

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Tozasertib

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Danusertib (PHA-739358)

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MLN8054

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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. MK-5108 (VX-689) induces autophagy. Phase 1.
Aurora A Inhibitor I (TC-S 7010)

Aurora A Inhibitor I (TC-S 7010) 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. Aurora A Inhibitor I (TC-S 7010) triggers apoptosis through the ROS-mediated UPR signaling pathway.

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Aurora Kinase Signaling Pathway Map

Biological Activity

Description

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	Mk\oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGjKflUxNjVizszN	NVT6Vo9QPzJiaB?=	NUPvfplsTE2VTx?=	M3myPWlEPTB;MD6wOEDPxE1?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
LS174T	MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NIS1cWUxNjVizszN	NIX5cWo4OiCq	NVLw[YZyTE2VTx?=	M4\YbWlEPTB;MD6wOUDPxE1?	MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
T84	NEPCW4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NVrze\|IxOC53IN88US=>	NF\m[JM4OiCq	NG[2TGVFVVOR	NF3EfnVKSzVyPUCuNFkh\|ryP	NW\SRm9VRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xN\|Y3QDRpPkK2NVM3Pjh2PD;hQi=>
LS180	Mnz0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NWf5OG53OC53IN88US=>	M3P6b\|czKGh?	MYPEUXNQ	M3\4TWlEPTB;MTFOwG0>	NET3R5E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN\|Y3QDR:L3G+
SW948	M3vIWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M1;SR\|AvPSEQvF2=	NH;CcpU4OiCq	MULEUXNQ	NYnsOGV[UUN3ME2xJO69VQ>?	Ml:5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
HCT15	M1nIPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NEDofIsxNjVizszN	MXW3NkBp	MWLEUXNQ	M3qySGlEPTB:MD60JO69VQ>?	M{L4b\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUO2Olg1Lz5{NkGzOlY5PDxxYU6=
DLD-1	Mnz0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M37RPVAvPSEQvF2=	NF7CVos4OiCq	M3jkfWROW09?	MWjJR\|UxRDBwODFOwG0>	MnzuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
MIP-101	NEfoPVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M4q2W\|AvPSEQvF2=	NXy5WFNjPzJiaB?=	Ml\ESG1UVw>?	MmPCTWM2OD1zIN88US=>	NUXsepVURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xN\|Y3QDRpPkK2NVM3Pjh2PD;hQi=>
SNU1544	M{D6U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NGTZTJMxNjVizszN	NIK4[Jc4OiCq	MWjEUXNQ	MYrJR\|UxRTFizszN	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
OCI-Ly10	MUDDfZRwfG:6aXOgRZN{[Xl?		MmPZO\|IhcA>?	MlvaSG1UVw>?	NFP1V4FKSzVyPUCuNFU5KM7:TR?=	M{DhUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
SU-DHL2	NVHCbohQS3m2b4TvfIlkKEG\|c3H5		MXm3NkBp	MYDEUXNQ	M2nXO2lEPTB;MD6wNUDPxE1?	NXrEOZE6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
OCI-LY7	MY\DfZRwfG:6aXOgRZN{[Xl?		MUG3NkBp	M4HIbWROW09?	NXK1RoU{UUN3ME2wMlA5OSEQvF2=	M1vreFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
SU-DHL6	NWHpUpNGS3m2b4TvfIlkKEG\|c3H5		NFWzRlU4OiCq	MnzwSG1UVw>?	M2nZXmlEPTB;MD60PFIh\|ryP	NI\PSFg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
Jeko-1	NG\meWZEgXSxdH;4bYMhSXO\|YYm=		M4DaVVczKGh?	M1\KTWROW09?	MonNTWM2OD1yLkCyPUDPxE1?	NIDR[oM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
JVM-2	M2jBcWN6fG:2b4jpZ{BCe3OjeR?=		NHr4emQ4OiCq	MVLEUXNQ	M4rjcGlEPTB;MD6wNUDPxE1?	M4O2WVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
Rec-1	MUDDfZRwfG:6aXOgRZN{[Xl?		MWS3NkBp	MY\EUXNQ	MWLJR\|UxRTBwMEi3JO69VQ>?	NUPyPFJVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
Z-138	M{fNW2N6fG:2b4jpZ{BCe3OjeR?=		NVTiR3FnPzJiaB?=	M4XjOWROW09?	MnzXTWM2OD1yLkCxN{DPxE1?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
H9	MnTyR5l1d3SxeHnjJGF{e2G7		NUn2fFUzPzJiaB?=	NH:3XlJFVVOR	NH3H[4NKSzVyPUCuOkDPxE1?	NETBfnc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
HH	NHnHd2VEgXSxdH;4bYMhSXO\|YYm=		NXzPTVVqPzJiaB?=	M4LEVmROW09?	MWXJR\|UxRTBwNzFOwG0>	M{DC[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
DND41	MYPDfZRwfG:6aXOgRZN{[Xl?		M2nvNFczKGh?	NI\yeXdFVVOR	MnvITWM2OD1yLkGg{txO	MlzqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
CCL119	MXHDfZRwfG:6aXOgRZN{[Xl?		M1TLfVczKGh?	NF3jWnhFVVOR	NXO5U\|B1UUN3ME2wMlA3OiEQvF2=	Mn2yQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
J.Cam 1.6	NGPrd4lEgXSxdH;4bYMhSXO\|YYm=		Mn3XO\|IhcA>?	NWrrSYY1TE2VTx?=	NYPuV\|VsUUN3ME2wMlExPSEQvF2=	MmnjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
Sup-T1	NG\HS45EgXSxdH;4bYMhSXO\|YYm=		Mmn3O\|IhcA>?	M3PX[WROW09?	MXXJR\|UxRTJwMUSyJO69VQ>?	M4DjU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
Tib 152	MnzoR5l1d3SxeHnjJGF{e2G7		MVq3NkBp	M3rYXGROW09?	NH7rc\|hKSzVyPUCuPEDPxE1?	NHrpWIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
MCF7	M2THU2Z2dmO2aX;uJGF{e2G7	MYW1JO69VQ>?	NFrFZYkzPCCq	M2jG[WROW09?	MXHJcoR2[2W\|IFeyM20h[XK{ZYP0	NX;RW\|R[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MDA-MB-231	MUfGeY5kfGmxbjDBd5NigQ>?	M2HDc\|Uh\|ryP	MV[yOEBp	MXzEUXNQ	MU\JcoR2[2W\|IFezM20h[XK{ZYP0	NYjHO3RnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MCF7	M3;6NWZ2dmO2aX;uJGF{e2G7	NFfObHU2KM7:TR?=	NVG0NnBCOjRiaB?=	MVTEUXNQ	MnHMSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET\|EwS0SFMh?=	NFz1bVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MCF7	MYnGeY5kfGmxbjDBd5NigQ>?	NYnZ[W1mPSEQvF2=	MnPzNlQhcA>?	Mm\ISG1UVw>?	M3;EemRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	MU\GeY5kfGmxbjDBd5NigQ>?	M2GzZ\|Uh\|ryP	Mny3NlQhcA>?	M3K3bmROW09?	NGjN[4NF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gZ5lkdGmwIFKx	NFfINFI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MCF7	NGnpeYxHfW6ldHnvckBCe3OjeR?=	NW\K[YVFPSEQvF2=	NYHofWd{OjRiaB?=	MY\EUXNQ	MWPJcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEKxJHdi\jFxQ3nwNS=>	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	NXy4UGVqTnWwY4Tpc44hSXO\|YYm=	NEj0NmU2KM7:TR?=	NX2xNpFMOjRiaB?=	M173dGROW09?	M1PMRWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?=	NELoSJU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	M4n4W2Z2dmO2aX;uJGF{e2G7	NYH1NHY3PSEQvF2=	M4Lub\|I1KGh?	NYTRW\|JmTE2VTx?=	M4PuNWRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsyN0OGQ{K=	M2Hp[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	NFrvfmRHfW6ldHnvckBCe3OjeR?=	NHrrS44yKM7:TR?=	NHzkN2wzPCCq	NWLiN41qTE2VTx?=	Ml\LTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET\|I>	M{T2Z\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	MoXqSpVv[3Srb36gRZN{[Xl?	M{jLXVUh\|ryP	MVGyOEBp	NF7MUoJFVVOR	MWrE[YNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiY4njcIlvKEJz	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MDA-MB-231	NHXUUZVHfW6ldHnvckBCe3OjeR?=	MXK1JO69VQ>?	NU\1bXZGOjRiaB?=	NHzzNGFFVVOR	MoDTTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE>	NIDnOXY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	M1uwbmZ2dmO2aX;uJGF{e2G7	NH3Jcm42KM7:TR?=	NUPjSHJPOjRiaB?=	MVfEUXNQ	NVS4c4ROUW6lcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJJAzPyCNaYCx	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MDA-MB-231	NGXYXndHfW6ldHnvckBCe3OjeR?=	M{LnOlUh\|ryP	NV;FV5psOjRiaB?=	NX70cpVQTE2VTx?=	NFztRXVKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFU{	M2K0VVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MCF7	NYX2S4xRSXCxcITvd4l{KEG\|c3H5	MVy1JO69VQ>?	Mo\QNlQhcA>?	MmDESG1UVw>?	M{LlPGlv\HWlZYOgZZBweHSxdHnjJIRm[XSq	MnX6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
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MCF7	MnPJSpVv[3Srb36gRZN{[Xl?	MVOxJO69VQ>?	MWO3NkBp	MWrEUXNQ	MXXJcoR2[2W\|IHH1eI9xcGGpaXOg[IVifGh?	NXPV[pk{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MDA-MB-231	NGfkOVhHfW6ldHnvckBCe3OjeR?=	M3H2dVEh\|ryP	NFvRcpY4OiCq	MYjEUXNQ	M1\kdGlv\HWlZYOgZZV1d3CqYXfpZ{Bl\WG2aB?=	M33i[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
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MG-63	MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NFP6dXA2OCEQvF2=	NH;FdY8zPCCq	NHTOR2hFVVOR	M3Gx[2lEPTB;OT61JO69VQ>?	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd7MkixNUc,OjV5OUK4NVE9N2F-
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BxPC-3	NIPCRotHfW6ldHnvckBCe3OjeR?=	MlG3OUDPxE1?	NFHqbokzPCCq	NXLqd3ZNTE2VTx?=	M2S4cGlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgbY4hTzJxTTDwbIF{\Q>?	NHzsU5Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[zNlIzPSd-MkW2N\|IzOjV:L3G+
PANC-1	MWfGeY5kfGmxbjDBd5NigQ>?	MXO1JO69VQ>?	NV3GPIkzOjRiaB?=	M2nOSWROW09?	M4j3R2lv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp	MnTvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4M{KyNlUoRjJ3NkOyNlI2RC:jPh?=
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OVCAR4	M1Hib2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NHXk[W0yODBizszN	MYOyOEBp	NVTQXmFDTE2VTx?=	NHjpVYhKSzVyPUKyMlE{KM7:TR?=	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ{NEe1NEc,OjV4MkS3OVA9N2F-
SKOV3	MWnGeY5kfGmxbjDBd5NigQ>?	NWfjR5hLPSEQvF2=	NVP0bGs1PzJiaB?=	M3rJZWROW09?	M2X4PWlv\HWlZYOgS\|IwVSCjcoLld5Q>	NH\BcpA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOFc2OCd-MkW2NlQ4PTB:L3G+
OVCAR4	M1LnT2Z2dmO2aX;uJGF{e2G7	NEW4dmo2KM7:TR?=	NFrRZnM4OiCq	MV7EUXNQ	MUDJcoR2[2W\|IFeyM20h[XK{ZYP0	NVS1PGM1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NlQ4PTBpPkK1OlI1PzVyPD;hQi=>
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NCI-N78	NELQfnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NUTzVmRqOjVizszN	NF;3eFEzPCCq	MonZSG1UVw>?	MYDJR\|UxRTJ4LkOzJO69VQ>?	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZyOUmyN{c,OjV4MEm5NlM9N2F-
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NCI-N78	NGnvNXZCeG:ydH;zbZMhSXO\|YYm=	MXS1JO69VQ>?	MkOzNlQhcA>?	MULEUXNQ	NIr0O\|RKdmS3Y3XzJIFxd3C2b4Ppdy=>	M{j2c\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkC5PVI{Lz5{NU[wPVkzOzxxYU6=
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GB169	NXvnRml4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	Ml7SNUDPxE1?	MVy3JIQ>	M3zsRmROW09?	NF\MbpVKSzVyPUCuNFMzKM7:TR?=	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTFyNkSyPEc,OjVzME[0Nlg9N2F-
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UM-UC-3	NWjZ[GJITnWwY4Tpc44hSXO\|YYm=	MYqxJO69VQ>?	NUXSSZB[PDhiaB?=	MorZSG1UVw>?	NG\zdnFKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	M1uzPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NECzOlM{Lz5{M{SwN\|Y{OzxxYU6=
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OVCAR-5	MlHTSpVv[3Srb36gRZN{[Xl?	MmSyOVAhdk1?			MVzJcohq[mm2czDj[YxtKG2rZ4LheIlwdg>?	MlntQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|M{SzNlcoRjJ\|M{O0N\|I4RC:jPh?=
SKOV3ip2	M3fpbmZ2dmO2aX;uJGF{e2G7	NVW4fXBCPTBibl2=			M{LsPWlvcGmkaYTzJINmdGxibXnndoF1cW:w	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN\|NEOyO{c,OjN\|M{SzNlc9N2F-
S462	MnXGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NUHG[ohWOTByIN88US=>	Mnz5O\|IhcA>?	MULEUXNQ	NI\4fXpCfHSnboXheIV{KGOnbHyg[5Jwf3Sq	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN{OEGxOEc,OjN\|MkixNVQ9N2F-
2884	NXm5RpdrT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NWTObWk6OTByIN88US=>	MWm3NkBp	MX\EUXNQ	MmnqRZR1\W63YYTld{Bk\WyuIHfyc5d1cA>?	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN{OEGxOEc,OjN\|MkixNVQ9N2F-
2885	M3Pofmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NVrPVWFmOTByIN88US=>	M3HhblczKGh?	NWTCWo9HTE2VTx?=	NVrRPHQzSXS2ZX71ZZRmeyClZXzsJIdzd3e2aB?=	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN{OEGxOEc,OjN\|MkixNVQ9N2F-
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TIB-48	NHvkS\|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	Ml;JNVAxKM7:TR?=		NWfmc5E{f2G2ZYK=	M1\lUGlEPTB;MD6wPFgh\|ryP	NHm5boI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{G1N\|UzPCd-MkOxOVM2OjR:L3G+
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OCL-AML2	M1zsR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MlHON{DPxE1?	MofFO\|IhcA>?		NI\1bIZFcW2rbnnzbIV{KGOnbHygeoli[mmuaYT5	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjR6OEK0PUc,OjJ2OEiyOFk9N2F-
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A-673	MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M17kXFExKM7:TR?=	M4PPV\|k3KGh?	M4DufGROW09?	Ml[4TWM2OD1yLkCzNkDPxE1?	MojsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF2NEi1PVEoRjJzNES4OVkyRC:jPh?=
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SK-N-MC	NEj1[mZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NGrRcpQyOCEQvF2=	M37PUVk3KGh?	NEfFToZFVVOR	MVnJR\|UxRTBwMEeyJO69VQ>?	Mlv5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF2NEi1PVEoRjJzNES4OVkyRC:jPh?=
CHLA-9	Ml;vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGGzSXEyOCEQvF2=	MnLOPVYhcA>?	Mlu3SG1UVw>?	M3G2N2lEPTB;MD6wNVgh\|ryP	M{jj[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNES4OVkyLz5{MUS0PFU6OTxxYU6=
CHLA-10	NE\IcpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NFK3fpYyOCEQvF2=	NHTKOGM6PiCq	NWrzeGN5TE2VTx?=	M3[2U2lEPTB;MD6wOlAh\|ryP	NUG0O5lxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG0OFg2QTFpPkKxOFQ5PTlzPD;hQi=>
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CHLA-90	MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MV2xNEDPxE1?	MmXSPVYhcA>?	MkXQSG1UVw>?	MnHYTWM2OD1yLkC2NUDPxE1?	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTR2OEW5NUc,OjF2NEi1PVE9N2F-
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CHLA-122	MmjvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NYHD[4tiOTBizszN	MUS5OkBp	M1vKUWROW09?	MUnJR\|UxRTBwMEG5JO69VQ>?	NHnsfZY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS0PFU6OSd-MkG0OFg2QTF:L3G+
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HCT116	NX;xeGJoS3m2b4TvfIlkcXS7IHHzd4F6				MWXDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[nliQoLkWUBqdmOxcoDvdoF1cW:wIHHzd4F6NCCJSUWwJF0hOC5yMzFOwG0v	M4HXblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUCxOVY1Lz5{NkGwNVU3PDxxYU6=
HCT116	M2PUVGZ2dmO2aX;uJIF{e2G7				MnPHTY5pcWKrdHnvckBw\iCjdYLvdoEhc2mwYYPlJGIhcW5iaIXtZY4hUEOWMUG2JINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiaHnzeI9v\SCKMzDwbI9{eGixconsZZRqd25iYomgbY1ufW6xZnz1c5Jme2OnbnPlJIFv[Wy7c3nzMEBKSzVyIE2gNU42KM7:TT6=	MnXkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMEG1OlQoRjJ4MUCxOVY1RC:jPh?=
BL21 (DE3) Rosetta	MnfUSpVv[3Srb36gZZN{[Xl?		MVyzNEBucW6\|		NWHPZ\|BLUW6qaXLpeIlwdiCxZjDIbZMufGGpZ3XkJIh2dWGwIFH1do9z[SCDIHvpcoF{\SBqMUKyJJRwKDRyIILld4llfWW\|KTDlfJBz\XO\|ZXSgbY4hTXOlaHXybYNpcWFiY3;sbUBDVDJzIDjESVMqKFKxc3X0eIEh[2WubIOgeZNqdmdiYnnveIlvgWyjdHXkJHNVUzJic4Xid5Rz[XSnIHnuZ5Vj[XSnZDDmc5IhOzBibXnud{BjgSCKVGLGJIF{e2G7LDDJR\|UxKD1iMD6wNFAxPCEQvF2u	NEnTPXg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{O5NVE{Oyd-MkezPVEyOzN:L3G+
HeLa Kyoto	NYP3V3loTnWwY4Tpc44h[XO\|YYm=		NXzvV\|NjOjBiaILz		NWH5b445UW6qaXLpeIlwdiCxZjDBeZJwemFiQjDrbY5ie2ViaX6gbJVu[W5iSHXMZUBMgW:2bzDj[YxteyCjc4Pld5Nm\CCjczDl[oZm[3Rib36g[Il{fHKrYoX0bY9vKG:oIIDod5Bpdy2qaYP0c45mKEh\|IIPldlExKGyndnXsJIlv[3WkYYTl[EBnd3JiMkCgbJJ{NCCLQ{WwJF0hOC5yMEG1JO69VS5?	NH\T[XI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{O5NVE{Oyd-MkezPVEyOzN:L3G+
HeLa Kyoto	MVzGeY5kfGmxbjDhd5NigQ>?		NWPXV\|duOjBiaILz		M3\CVGlvcGmkaYTpc44hd2ZiQYXyc5JiKEFia3nuZZNmKGG3dH;wbI9{eGixconsZZRqd25iYYSgWIhzOjh6IHnuJIh2dWGwIFjlUIEhU3mxdH:gZ4VtdHNiaX7jeYJifGWmIH\vdkAzOCCqcoOsJGlEPTBiPTCwMlAxPjdizszNMi=>	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzN7MUGzN{c,Ojd\|OUGxN\|M9N2F-
multiple myeloma	MofWSpVv[3Srb36gZZN{[Xl?				M1G3UHN2eHC{ZYPzbY9vKG:oIHPlcIwhdWm2b4Ppd{BqdiCqdX3hckBufWy2aYDs[UBugWWub33hJINmdGy\|LDDJR\|UxKD1iMD6wNFMh\|ryPLh?=	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDlzOEC5Okc,Ojh7MUiwPVY9N2F-
Calu6	NHznZ4hCdnSrdIXtc5Ih[XO\|YYm=	M2\mbFIxKG2pL3vn	NXTtS3dWOjFiZHH5dy=>		MUjBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCFYXz1OkBk\WyuczD4[Y5w\3KjZoTl[EBqdiCvb4Xz[UBie3Onc4Pl[EBieyC2dX3vdkBoem:5dHigbY5pcWKrdHnvckBifCB{MDDt[{9s\yxicH:gZollKGGmbXnubZN1\XKnZDDmc5IhOjFiZHH5dy=>	NIX5c\|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGwNVU3PCd-Mk[xNFE2PjR:L3G+
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MDA-MB-231	NFLISHdHfW6ldHnvckBie3OjeR?=	MmnlNUB2VQ>?	MWq0PEBpenN?		NXLh[IxNUW6mdXP0bY9vKG:oIHPodo9ud3OxbXWgZYxq\26vZX70JIRm\mWldIOgbY4hcHWvYX6gUWRCNU2ELUKzNUBk\WyuczDheEAyKHWPIHHmeIVzKDR6IHjyd{BjgSCGQWDJJJN1[WmwaX7nJIJie2WmIHntcZVvd2[udX;y[ZNk\W6lZTDhd5NigQ>?	M2K5e\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{W4NVQ4Lz5{OUO1PFE1PzxxYU6=
MDA-MB-231	Mmi0SpVv[3Srb36gZZN{[Xl?	NF65O\|EyKHWP	NGrqcFk1QCCqcoO=		MVrJcoR2[3Srb36gc4Yh[WKncoLhcpQhe3CrbnTs[UBnd3KvYYTpc44hf2m2aDD0dolxd2yjcjDhcoQhfGW2cnHwc4xieiCxY3P1dpJmdmOnIHnuJIh2dWGwIF3ERU1OSi1{M{GgZ4VtdHNiYYSgNUB2VSCjZoTldkA1QCCqcoOgZpkhTEGSSTDzeIFqdmmwZzDiZZNm\CCrbX31co9ndHWxcnXzZ4Vv[2ViYYPzZZk>	MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTN3OEG0O{c,Ojl\|NUixOFc9N2F-
MDA-MB-231	MYnGeY5kfGmxbjDhd5NigQ>?	M{DDW\|AvPSC3TR?=	NUjoeFdIPDhiaILz		NELjWnRKdmirYnn0bY9vKG:oIHHsdIhiNXS3YoXsbY4hcW5iaIXtZY4hVUSDLV3CMVI{OSClZXzsd{Bie3Onc4Pl[EBieyCjYn;sbZNpdWWwdDDv[kBz\We3bHHyJIxw[2G2aX;uJI9nKHC{b4TlbY4h[XRiMD61JJVOKGGodHXyJFQ5KGi{czDifUBFSVCLIIP0ZYlvcW6pIHLhd4VlKGmvbYXuc4ZtfW:{ZYPj[Y5k\SCjc4PhfS=>	MmK2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl\|NUixOFcoRjJ7M{W4NVQ4RC:jPh?=
MDA-MB-231	NIPLfXVHfW6ldHnvckBie3OjeR?=	NYrvVpVqOC53IIXN	NV3GNoxVPDhiaILz		MojYTY5pcWKrdHnvckBw\iCDVWLLRUBqdiCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIF{e2W\|c3XkJIF{KGGkb3zpd4hu\W62IH;mJJJm\3WuYYKgcI9k[XSrb36gc4YheHKxdHXpckBifCByLkWgeW0h[W[2ZYKgOFghcHK\|IHL5JGRCWElic4ThbY5qdmdiYnHz[YQhcW2vdX7v[ox2d3Knc3PlcoNmKGG\|c3H5	M1;tNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{W4NVQ4Lz5{OUO1PFE1PzxxYU6=
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NB1643	MkTFdWhVWyCjc4PhfS=>				MmD4dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	M3fNXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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MG 63 (6-TG R)	NGi1ZphyUFSVIHHzd4F6				NXj5O5ZueUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
U-2 OS	NG\wcmpyUFSVIHHzd4F6				MUfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDVMVIhV1NiY3XscJM>	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SJ-GBM2	MoHhdWhVWyCjc4PhfS=>				M1zkdZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz	NX34[nZVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC	M{HGV5FJXFNiYYPzZZk>				MVzxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB-EBc1	NWmyWXMxeUiWUzDhd5NigQ>?				MVrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	NWHmNWdVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5	MYLxTHRUKGG\|c3H5				MoK2dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEyDTj21JINmdGy\|	NIPXe5o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh18	MorFdWhVWyCjc4PhfS=>				Mn\ndWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqMUigZ4VtdHN?	MoDlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	M3f5[JFJXFNiYYPzZZk>				MnfmdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV2suVi2PQzDj[Yxtew>?	M4\PZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32	NFTBOHZyUFSVIHHzd4F6				M33rSJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHREOzJiY3XscJM>	NWjud\|hpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2	NInZU2VyUFSVIHHzd4F6				MYfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTZY9{NTJiY3XscJM>	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	p-AURKA(T288) / p-EIF4E(S209) / c-Myc ; phospho-Aurora A / Aurora B ; H3S10P / H3K27me2 / H3K27me3 / H3K9me2 / H3AcK / H4K16Ac	28073841 22863010 29477140
Growth inhibition assay	Cell viability	25632225
Immunofluorescence	acetylated α-tubulin / γ-tubulin ; E-cadherin / β-catenin / vimentin / p-SMAD5 ; Centrin-2 / tubulin ; phospho-Aurora A(T288)	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 (from reference)

Kinase Assay:^[1]	Aurora A radioactive Flashplate enzyme assay: Aurora A radioactive Flashplate enzyme assay is conducted to determine the nature and degree of MLN8237-mediated inhibition in vitro. Recombinant Aurora A is expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A is conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) is assayed in 50 mM Hepes (pH 7.5), 10 mM MgCl₂, 5 mM DTT, 0.05% Tween 20, 2 μM peptide substrate, 3.3 μCi/mL [γ-³³P]ATP at 2 μM, and increasing concentrations of MLN8237 by using Image FlashPlates.
Cell Research:^[2]	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.
Animal Research:^[2]	Animal Models: Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells Dosages: ~30 mg/kg/day Administration: Orally

References

Solubility (25°C)

In vitro


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. Click to purchase: PEG300 Tween 80	6mg/mL

Chemical Information

Molecular Weight	518.92
Formula	C₂₇H₂₀ClFN₄O₄
CAS No.	1028486-01-2
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC

Download Alisertib (MLN8237) SDF

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Dilution Calculator Molecular Weight Calculator

Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04479306	Active not 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

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

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.

Handling Instructions

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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.

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