Alisertib (MLN8237)

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.

Alisertib (MLN8237) Chemical Structure

CAS No. 1028486-01-2

Selleck's Alisertib (MLN8237) has been cited by 287 publications

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Other Aurora Kinase Products

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. Alisertib induces cell cycle arrest, apoptosis and autophagy. 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>? 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-
MDA-MB-231 M3jRSWFxd3C2b4Ppd{BCe3OjeR?= M1LRW|Uh|ryP MYCyOEBp MoLiSG1UVw>? MXnJcoR2[2W|IHHwc5B1d3SrYzDk[YF1cA>? MlLqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MCF7 NGrPTVRHfW6ldHnvckBCe3OjeR?= MUOxJO69VQ>? MWe3NkBp NFmxd5hFVVOR M1Ph[Wlv\HWlZYOgZZV1d3CqYXfpZ{Bl\WG2aB?= M4f4XlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231 MVzGeY5kfGmxbjDBd5NigQ>? MkLyNUDPxE1? M{n2[|czKGh? NYLEOVJqTE2VTx?= NIe0VJFKdmS3Y3XzJIF2fG:yaHHnbYMh\GWjdHi= M4DyelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
U-2 OS NUPUNFFiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoLwOVAh|ryP Mm\YNlQhcA>? NHfXOFJFVVOR MWjJR|UxRTF4Lk[g{txO Ml7jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5OUK4NVEoRjJ3N{myPFEyRC:jPh?=
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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?=
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)

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.

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
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

In vivo Formulation Calculator (Clear solution)

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

mg/kg g μL

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

Mass Concentration Volume Molecular Weight

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

Tel: +1-832-582-8158 Ext:3
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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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