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Alisertib (MLN8237)

Name: Alisertib (MLN8237)
Brand: Selleck Chemicals
SKU: S1133
Rating: 5 (287 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 287 publications

Purity & Quality Control

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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	MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MViwMlUh\|ryP	MYq3NkBp	M{XQeGROW09?	NFXV[YlKSzVyPUCuNFQh\|ryP	MnjnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
LS174T	MkW4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NHi4TZoxNjVizszN	M3HQVlczKGh?	M4rK[WROW09?	Mn\QTWM2OD1yLkC1JO69VQ>?	Ml25QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
T84	NIPOcFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NYDNcHM3OC53IN88US=>	NUnrVJJJPzJiaB?=	NVLrNHJ{TE2VTx?=	M2XvN2lEPTB;MD6wPUDPxE1?	NXXCWJdIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xN\|Y3QDRpPkK2NVM3Pjh2PD;hQi=>
LS180	MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MknoNE42KM7:TR?=	MlLUO\|IhcA>?	NGrQfYhFVVOR	NYXIN3JMUUN3ME2xJO69VQ>?	NIPrfYQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN\|Y3QDR:L3G+
SW948	NUDXTGc2T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NGX2PHkxNjVizszN	NF7KU4k4OiCq	MoTESG1UVw>?	NEC5S5BKSzVyPUGg{txO	Mlr4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
HCT15	NIL1WXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M{PObVAvPSEQvF2=	NYLvdXRPPzJiaB?=	MnHjSG1UVw>?	M2D2RWlEPTB:MD60JO69VQ>?	MmjvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
DLD-1	MmDnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MkK3NE42KM7:TR?=	NUXLdIRMPzJiaB?=	MorYSG1UVw>?	MUHJR\|UxRDBwODFOwG0>	NWrJbIZ2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xN\|Y3QDRpPkK2NVM3Pjh2PD;hQi=>
MIP-101	NXXYZnU1T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NHnjeo0xNjVizszN	NWfQXVdQPzJiaB?=	MoTWSG1UVw>?	NV;hUmg2UUN3ME2xJO69VQ>?	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
SNU1544	MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MnGwNE42KM7:TR?=	M3nmNlczKGh?	NYjKUGhwTE2VTx?=	NX;4XIlCUUN3ME2xJO69VQ>?	NH7YbVU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN\|Y3QDR:L3G+
OCI-Ly10	NVi4cIFCS3m2b4TvfIlkKEG\|c3H5		M2DHWVczKGh?	MVHEUXNQ	M3zyc2lEPTB;MD6wOVgh\|ryP	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
SU-DHL2	MlX0R5l1d3SxeHnjJGF{e2G7		Mor6O\|IhcA>?	MUnEUXNQ	NHvjc\|FKSzVyPUCuNFEh\|ryP	M1;t[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
OCI-LY7	MmWwR5l1d3SxeHnjJGF{e2G7		NULPfWJ7PzJiaB?=	NWe2eo1vTE2VTx?=	M2f3bWlEPTB;MD6wPFEh\|ryP	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
SU-DHL6	Mn\nR5l1d3SxeHnjJGF{e2G7		M4rXR\|czKGh?	NXWxUlk2TE2VTx?=	M3fJSWlEPTB;MD60PFIh\|ryP	M1T0TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
Jeko-1	Mn;aR5l1d3SxeHnjJGF{e2G7		MXy3NkBp	M3rBWWROW09?	MX;JR\|UxRTBwMEK5JO69VQ>?	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
JVM-2	NXmzZW1bS3m2b4TvfIlkKEG\|c3H5		NVHMNGs2PzJiaB?=	NGnL[mpFVVOR	NHP6dJdKSzVyPUCuNFEh\|ryP	M4rLW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
Rec-1	MlHCR5l1d3SxeHnjJGF{e2G7		M13DUFczKGh?	Mkf1SG1UVw>?	NYHn[Xp4UUN3ME2wMlA5PyEQvF2=	NYjSemI6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
Z-138	MVzDfZRwfG:6aXOgRZN{[Xl?		NG[yNnM4OiCq	M1jZZWROW09?	Mnv0TWM2OD1yLkCxN{DPxE1?	M4C5R\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
H9	NGiybIlEgXSxdH;4bYMhSXO\|YYm=		MVm3NkBp	NVrnVWgxTE2VTx?=	M4fodmlEPTB;MD62JO69VQ>?	MmfqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
HH	MmDzR5l1d3SxeHnjJGF{e2G7		NVjKZ2tyPzJiaB?=	MXXEUXNQ	M1rhb2lEPTB;MD63JO69VQ>?	M{j5Z\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
DND41	MU\DfZRwfG:6aXOgRZN{[Xl?		M2nlV\|czKGh?	NWHVPG93TE2VTx?=	MYfJR\|UxRTBwMTFOwG0>	MkfpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
CCL119	NUnER5VCS3m2b4TvfIlkKEG\|c3H5		NVmxVopVPzJiaB?=	MVLEUXNQ	M4iwWGlEPTB;MD6wOlIh\|ryP	NYT5OJN6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
J.Cam 1.6	M3TBVGN6fG:2b4jpZ{BCe3OjeR?=		MkjPO\|IhcA>?	NVXIeY5{TE2VTx?=	NIDX[I1KSzVyPUCuNVA2KM7:TR?=	M4XwXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
Sup-T1	MknLR5l1d3SxeHnjJGF{e2G7		MkewO\|IhcA>?	M{TSdGROW09?	NULjR5Y4UUN3ME2yMlE1OiEQvF2=	NInXR4g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
Tib 152	NF7OcFlEgXSxdH;4bYMhSXO\|YYm=		MoHKO\|IhcA>?	M4TvemROW09?	NHTJZ5dKSzVyPUCuPEDPxE1?	NUXnUY9GRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
MCF7	MkO2SpVv[3Srb36gRZN{[Xl?	NWXwUI9mPSEQvF2=	NECwbYEzPCCq	M1myeGROW09?	MoPRTY5lfWOnczDHNk9OKGG{cnXzeC=>	NIHmSJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	MlviSpVv[3Srb36gRZN{[Xl?	M3XRN\|Uh\|ryP	MlTyNlQhcA>?	NHTNZlNFVVOR	MVrJcoR2[2W\|IFezM20h[XK{ZYP0	NInrOZY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MCF7	NH;2NY1HfW6ldHnvckBCe3OjeR?=	NVewcoR{PSEQvF2=	MUKyOEBp	M3TzOGROW09?	Ml;RSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET\|EwS0SFMh?=	NIWyR4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MCF7	NHT5fppHfW6ldHnvckBCe3OjeR?=	MmHCOUDPxE1?	NWjNeIpSOjRiaB?=	M3u2[WROW09?	NULYb\|BYTGWlcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJGNFUzJ?	NFmzeXA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MCF7	NFLG[Y9HfW6ldHnvckBCe3OjeR?=	MVe1JO69VQ>?	M2LET\|I1KGh?	NWX5ZW9TTE2VTx?=	MX;E[YNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiY4njcIlvKEJz	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	M2\iU2Z2dmO2aX;uJGF{e2G7	NX31VXFHPSEQvF2=	NHiwSoozPCCq	NIrm[VVFVVOR	M1LIS2lv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlEhX2GoMT;DbZAy	M3LjZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MCF7	M2n6[mZ2dmO2aX;uJGF{e2G7	MVm1JO69VQ>?	MWKyOEBp	MXfEUXNQ	MVvJcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF?	M3TGdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	M3LrV2Z2dmO2aX;uJGF{e2G7	NIr6RY82KM7:TR?=	Mk\mNlQhcA>?	MU\EUXNQ	NHq0NldF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOS:FRFOy	NWTkSYh5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MDA-MB-231	NXLpSlN2TnWwY4Tpc44hSXO\|YYm=	NHnZTXoyKM7:TR?=	MXiyOEBp	MlnOSG1UVw>?	NWDKdGdsUW6lcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJGNFUzJ?	M2H0UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	NWTQWlhYTnWwY4Tpc44hSXO\|YYm=	MmrCOUDPxE1?	M{HEfVI1KGh?	MWHEUXNQ	NWL4ZXVYTGWlcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJIN6[2yrbjDCNS=>	M2nTT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	MlPFSpVv[3Srb36gRZN{[Xl?	NFv5XJY2KM7:TR?=	MlT2NlQhcA>?	NXTBd2h[TE2VTx?=	MX\JcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEKxJHdi\jFxQ3nwNS=>	NEfSWmo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	NE\Uc4JHfW6ldHnvckBCe3OjeR?=	MUK1JO69VQ>?	NHmxOmozPCCq	MlfqSG1UVw>?	MUTJcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF?	M1fSNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	NHXmXGhHfW6ldHnvckBCe3OjeR?=	MmLSOUDPxE1?	NHLvWmgzPCCq	MVzEUXNQ	NYHnUVQ{UW6lcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJJA2Ow>?	NYDPUYhIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MCF7	NUPmSHdYSXCxcITvd4l{KEG\|c3H5	Ml\uOUDPxE1?	NHvOWlAzPCCq	MXjEUXNQ	MUXJcoR2[2W\|IHHwc5B1d3SrYzDk[YF1cA>?	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
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CHLA-9	MkLlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M1zZblExKM7:TR?=	NIi1Wmk6PiCq	M2TIN2ROW09?	NGG5TlJKSzVyPUCuNFE5KM7:TR?=	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTR2OEW5NUc,OjF2NEi1PVE9N2F-
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MKN45	NVHaNpdFSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M3fVeFczKGi{cx?=		MnPlRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPS160OUBk\WyuczDh[pRmeiB5MjDodpMh[nliV2PUPEBie3OjeTygTWM2OCB;IECuNFk{KM7:TT6=	NHzR[oo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOVYyPyd-MkW2NlU3OTd:L3G+
HCT116	MmDhRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		Ml[2O\|IhcHK\|		M36yUWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDXV3Q5KGG\|c3H5MEBKSzVyIE2gNE4xQTVizszNMi=>	NGDPeFk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOVYyPyd-MkW2NlU3OTd:L3G+
Lu116	NGr2XZBCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M4fDZVczKGi{cx?=		M{i4O2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTIWxNVYh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IGfTWFgh[XO\|YYmsJGlEPTBiPTCwMlA6PyEQvF2u	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ{NU[xO{c,OjV4MkW2NVc9N2F-
NCI-H358	NIHuN4pCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		MUi3NkBpenN?		M{LiUmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWg{PThiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JHdUXDhiYYPzZZktKEmFNUCgQUAxNjFizszNMi=>	MorFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4MkW2NVcoRjJ3NkK1OlE4RC:jPh?=
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HT-29	NX32c2R4SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MX[3NkBpenN?		MlrVRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKVD2yPUBk\WyuczDh[pRmeiB5MjDodpMh[nliV2PUPEBie3OjeTygTWM2OCB;IECuN\|Mh\|ryPLh?=	NFu0R3Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOVYyPyd-MkW2NlU3OTd:L3G+
HCT15	NUT1T4NISW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NXjBe3VQPzJiaILz		M{js[2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVUh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IGfTWFgh[XO\|YYmsJGlEPTBiPTCwMlc1KM7:TT6=	NYSxeoVPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NlU3OTdpPkK1OlI2PjF5PD;hQi=>
Sf9	MorTSpVv[3Srb36gZZN{[Xl?				MmLwR49ueGW2aYTpeoUhcW6qaXLpeIlwdiCxZjDy[YNwdWKrbnHueEBud3W\|ZTDheZJwemFia3nuZZNmKEFiZYjwdoV{e2WmIHnuJIlve2WldDDT[lkh[2WubIOgbY4heHKnc3XuZ4Uhd2ZiQWTQMEBMcSB;IECuNFAxOyEQvF2u	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFyMUW2OEc,OjZzMEG1OlQ9N2F-
Sf9	MWLGeY5kfGmxbjDhd5NigQ>?				MW\Jcohq[mm2aX;uJI9nKHKnY3;tZolv[W62IH3veZNmKGG3cn;yZUBscW6jc3WgRUBmgHC{ZYPz[YQhcW5iaX7z[YN1KFOoOTDj[YxteyC3c3nu[{BjcW:2aX6tS2xTWkGVTFegZZMhe3Wkc4TyZZRmKGmwIIDy[ZNmdmOnIH;mJHto[W2vYT2zN3BeSVSSLDDJR\|UxKD1iMD6wNFEh\|ryPLh?=	MlW3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMEG1OlQoRjJ4MUCxOVY1RC:jPh?=
HCT116	NVnLUXB5TnWwY4Tpc44h[XO\|YYm=				NWjteGVTUW6qaXLpeIlwdiCxZjDheZJwemFia3nuZZNmKEFiYYX0c5Bpd3OyaH;yfYxifGmxbjDheEBVOjh6IHnuJIh2dWGwIFjDWFEyPiClZXzsd{BjgSCrbX31co9ndHWxcnXzZ4Vv[2ViYX7hcJl{cXNuIFnDOVAhRSByLkCwO{DPxE1w	NUXYPHZmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNFE2PjRpPkK2NVAyPTZ2PD;hQi=>
HCT116	MXHDfZRwfG:6aXPpeJkh[XO\|YYm=				MYDDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[nliQoLkWUBqdmOxcoDvdoF1cW:wIHHzd4F6NCCJSUWwJF0hOC5yMzFOwG0v	MnfGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMEG1OlQoRjJ4MUCxOVY1RC:jPh?=
HCT116	NYe4RWwzTnWwY4Tpc44h[XO\|YYm=				NY\aOGJ5UW6qaXLpeIlwdiCxZjDheZJwemFia3nuZZNmKEJiaX6gbJVu[W5iSFPUNVE3KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gbIl{fG:wZTDIN{BxcG:\|cHjvdplt[XSrb36gZpkhcW2vdX7v[ox2d3Knc3PlcoNmKGGwYXz5d4l{NCCLQ{WwJF0hOS53IN88UU4>	Mon4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzMEG1OlQoRjJ4MUCxOVY1RC:jPh?=
BL21 (DE3) Rosetta	MnrtSpVv[3Srb36gZZN{[Xl?		MkT2N\|AhdWmwcx?=		NVfId\|c1UW6qaXLpeIlwdiCxZjDIbZMufGGpZ3XkJIh2dWGwIFH1do9z[SCDIHvpcoF{\SBqMUKyJJRwKDRyIILld4llfWW\|KTDlfJBz\XO\|ZXSgbY4hTXOlaHXybYNpcWFiY3;sbUBDVDJzIDjESVMqKFKxc3X0eIEh[2WubIOgeZNqdmdiYnnveIlvgWyjdHXkJHNVUzJic4Xid5Rz[XSnIHnuZ5Vj[XSnZDDmc5IhOzBibXnud{BjgSCKVGLGJIF{e2G7LDDJR\|UxKD1iMD6wNFAxPCEQvF2u	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzN7MUGzN{c,Ojd\|OUGxN\|M9N2F-
HeLa Kyoto	MlH2SpVv[3Srb36gZZN{[Xl?		NWnDZXBoOjBiaILz		MofsTY5pcWKrdHnvckBw\iCDdYLvdoEhSiCtaX7hd4UhcW5iaIXtZY4hUGWOYTDLfY91dyClZXzsd{Bie3Onc4Pl[EBieyCnZn\lZ5Qhd25iZHnzeJJq[nW2aX;uJI9nKHCqc4Doc{1pcXO2b37lJGg{KHOnckGwJIxmfmWuIHnuZ5Vj[XSnZDDmc5IhOjBiaILzMEBKSzVyIE2gNE4xODF3IN88UU4>	M1vhR\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5M{mxNVM{Lz5{N{O5NVE{OzxxYU6=
HeLa Kyoto	NVLQS5ZtTnWwY4Tpc44h[XO\|YYm=		MkjBNlAhcHK\|		MnPTTY5pcWKrdHnvckBw\iCDdYLvdoEhSSCtaX7hd4Uh[XW2b4Doc5NxcG:{eXzheIlwdiCjdDDUbJIzQDhiaX6gbJVu[W5iSHXMZUBMgW:2bzDj[YxteyCrbnP1ZoF1\WRiZn;yJFIxKGi{czygTWM2OCB;IECuNFA3PyEQvF2u	M3;n[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5M{mxNVM{Lz5{N{O5NVE{OzxxYU6=
multiple myeloma	Mo\3SpVv[3Srb36gZZN{[Xl?				Ml;NV5VxeHKnc4Ppc44hd2ZiY3XscEBucXSxc3nzJIlvKGi3bXHuJI12dHSrcHzlJI16\WyxbXGgZ4VtdHNuIFnDOVAhRSByLkCwN{DPxE1w	NVLiemRWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki5NVgxQTZpPkK4PVE5ODl4PD;hQi=>
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HeLa Kyoto	Mn7uSpVv[3Srb36gZZN{[Xl?	NYK1epR3OC5{NTD1US=>	NXLzVFZ4OjBiaILz		MXrJcohq[mm2aX;uJI9nKEG3cn;yZUBCKGurbnHz[UBtd2OjbHn6ZZRqd25iYYSgd5BqdmSuZTDtbYNzd3S3YoXs[ZMhcW5iaIXtZY4hUGWOYTDLfY91dyClZXzsd{BifCByLkK1JJVOKGmwY4XiZZRm\CCob4KgNlAhcHK\|	Mm\zQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd\|OUGxN\|MoRjJ5M{mxNVM{RC:jPh?=
MDA-MB-231	NEDJNplHfW6ldHnvckBie3OjeR?=	NEHDb3cyKHWP	NIfic4E1QCCqcoO=		NGC5RpFKdmS3Y4Tpc44hd2ZiY3jyc41we2:vZTDhcIlodm2nboSg[IVn\WO2czDpckBpfW2jbjDNSGEuVUJvMkOxJINmdGy\|IHH0JFEhfU1iYX\0[ZIhPDhiaILzJIJ6KESDUFmgd5RicW6rbnegZoF{\WRiaX3teY5w\my3b4Lld4NmdmOnIHHzd4F6	NVTSd3kyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmzOVgyPDdpPkK5N\|U5OTR5PD;hQi=>
MDA-MB-231	MoXwSpVv[3Srb36gZZN{[Xl?	NYjINoZYOSC3TR?=	NF\rcpo1QCCqcoO=		NFHyTmRKdmS3Y4Tpc44hd2ZiYXLldpJidnRic4DpcoRt\SCob4LtZZRqd25id3n0bEB1emmyb3zhdkBidmRidHX0doFxd2yjcjDvZ4N2enKnbnPlJIlvKGi3bXHuJG1FSS2PQj2yN\|Eh[2WubIOgZZQhOSC3TTDh[pRmeiB2ODDodpMh[nliRFHQTUB{fGGrbnnu[{Bj[XOnZDDpcY12dm:obIXvdoV{[2WwY3WgZZN{[Xl?	MoTBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl\|NUixOFcoRjJ7M{W4NVQ4RC:jPh?=
MDA-MB-231	MmP4SpVv[3Srb36gZZN{[Xl?	MX[wMlUhfU1?	NWjD[JNPPDhiaILz		MmPsTY5pcWKrdHnvckBw\iCjbIDoZU11fWK3bHnuJIlvKGi3bXHuJG1FSS2PQj2yN\|Eh[2WubIOgZZN{\XO\|ZXSgZZMh[WKxbHnzbI1mdnRib3[gdoVofWyjcjDsc4NifGmxbjDv[kBxem:2ZXnuJIF1KDBwNTD1UUBi\nSncjC0PEBpenNiYomgSGFRUSC\|dHHpcolv\yCkYYPl[EBqdW23bn;mcJVwemW\|Y3XuZ4Uh[XO\|YYm=	M1:3XVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{W4NVQ4Lz5{OUO1PFE1PzxxYU6=
MDA-MB-231	MXTGeY5kfGmxbjDhd5NigQ>?	NFXaSpcxNjVidV2=	MljTOFghcHK\|		MXHJcohq[mm2aX;uJI9nKEGXUlvBJIlvKGi3bXHuJG1FSS2PQj2yN\|Eh[2WubIOgZZN{\XO\|ZXSgZZMh[WKxbHnzbI1mdnRib3[gdoVofWyjcjDsc4NifGmxbjDv[kBxem:2ZXnuJIF1KDBwNTD1UUBi\nSncjC0PEBpenNiYomgSGFRUSC\|dHHpcolv\yCkYYPl[EBqdW23bn;mcJVwemW\|Y3XuZ4Uh[XO\|YYm=	MlPBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl\|NUixOFcoRjJ7M{W4NVQ4RC:jPh?=
TC32	NF3kZVhyUFSVIHHzd4F6				MV\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXEN\|MjDj[Yxtew>?	MlfWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Saos-2	MVjxTHRUKGG\|c3H5				M4nRVJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVYX;zMVIh[2WubIO=	NWfpNGt5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
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MG 63 (6-TG R)	NFrhPYdyUFSVIHHzd4F6				MWTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	NVTUbpVSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643	MVvxTHRUKGG\|c3H5				MYfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJzNkSzJINmdGy\|	MoLUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1	NHXBemdyUFSVIHHzd4F6				NU\rWnpReUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	NGG2Nlk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
MG 63 (6-TG R)	MnP1dWhVWyCjc4PhfS=>				MWPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDNS{A3OyBqNj3US{BTMSClZXzsdy=>	M4nYblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
U-2 OS	M1u3WZFJXFNiYYPzZZk>				NGfuXGxyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBWNTJiT2OgZ4VtdHN?	Mln0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SJ-GBM2	NV\vbmR5eUiWUzDhd5NigQ>?				NInxW\|JyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1qtS2JOOiClZXzsdy=>	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	NILzeWFyUFSVIHHzd4F6				MYrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	M{nlZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB-EBc1	NVrGXJpqeUiWUzDhd5NigQ>?				Mki2dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6ELVXCZ\|Eh[2WubIO=	NHzFOoY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
LAN-5	M4PDNZFJXFNiYYPzZZk>				MX;xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN?	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh18	NWrORZRReUiWUzDhd5NigQ>?				M13HR5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEG4JINmdGy\|	M3HWOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-MC	MXrxTHRUKGG\|c3H5				MV\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTT{1PNU2FIHPlcIx{	M{PoVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32	MX7xTHRUKGG\|c3H5				M37ReZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHREOzJiY3XscJM>	M13i[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2	MlPKdWhVWyCjc4PhfS=>				NXPM[VE2eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW2Gxcz2yJINmdGy\|	MoC0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=

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. (Only for Reference)
Animal Research:^[2]	Animal Models: Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells 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. Click to purchase: PEG300 Tween 80	6mg/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

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	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 2022-01-17)

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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