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Alisertib (MLN8237)

For research use only.

Catalog No.S1133

235 publications

Alisertib (MLN8237) Chemical Structure

CAS No. 1028486-01-2

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.

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Selleck's Alisertib (MLN8237) has been cited by 235 publications

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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. 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 MoLUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MonDNE42KM7:TR?= NGDhR|E4OiCq MmH2SG1UVw>? MoTuTWM2OD1yLkC0JO69VQ>? NEXPR3Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN|Y3QDR:L3G+
LS174T NIn3VJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFS3Z24xNjVizszN Mln1O|IhcA>? M4LQfmROW09? Ml7sTWM2OD1yLkC1JO69VQ>? NEXSfXg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN|Y3QDR:L3G+
T84 Mm\RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWqwMlUh|ryP MYe3NkBp MmnySG1UVw>? NHv0NVNKSzVyPUCuNFkh|ryP NIDod2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN|Y3QDR:L3G+
LS180 NFrNZWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4LQTlAvPSEQvF2= Mn\5O|IhcA>? NGHoOndFVVOR NYHhU49UUUN3ME2xJO69VQ>? MnvTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
SW948 MnnWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUPxPHRmOC53IN88US=> MUO3NkBp M3KzOmROW09? M2XMeGlEPTB;MTFOwG0> NELDbno9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN|Y3QDR:L3G+
HCT15 NVzqNWt[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHINE42KM7:TR?= NF3Pcmo4OiCq M4nGbGROW09? NFHKPIFKSzVyPECuOEDPxE1? NV3jdlA4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xN|Y3QDRpPkK2NVM3Pjh2PD;hQi=>
DLD-1 M2fZUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUGwMlUh|ryP NHz4eWE4OiCq NHXnUGNFVVOR M3\KXmlEPTB:MD64JO69VQ>? MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF|Nk[4OEc,OjZzM{[2PFQ9N2F-
MIP-101 NWfQOIdqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4q3fFAvPSEQvF2= M3q5VlczKGh? M2T2OmROW09? M1PFcWlEPTB;MTFOwG0> MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF|Nk[4OEc,OjZzM{[2PFQ9N2F-
SNU1544 M1y2RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWOwMlUh|ryP MV[3NkBp NWS3boVOTE2VTx?= MmnuTWM2OD1zIN88US=> MlPVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
OCI-Ly10 MWPDfZRwfG:6aXOgRZN{[Xl? M2\wUVczKGh? NGj6cphFVVOR NF74d5ZKSzVyPUCuNFU5KM7:TR?= MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN|E9N2F-
SU-DHL2 NEXJ[VVEgXSxdH;4bYMhSXO|YYm= NGTlOWk4OiCq MWLEUXNQ MVXJR|UxRTBwMEGg{txO NFT5[IE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O|g{OzF:L3G+
OCI-LY7 NX3QTlZmS3m2b4TvfIlkKEG|c3H5 MVS3NkBp MomzSG1UVw>? MX;JR|UxRTBwMEixJO69VQ>? M4D5eVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N|MyLz5{NUi3PFM{OTxxYU6=
SU-DHL6 MXLDfZRwfG:6aXOgRZN{[Xl? NWDTWHA1PzJiaB?= NI\RTHhFVVOR NX7oW|Q4UUN3ME2wMlQ5OiEQvF2= NHvoNXI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O|g{OzF:L3G+
Jeko-1 NWrn[phDS3m2b4TvfIlkKEG|c3H5 M161TVczKGh? MYnEUXNQ M3LaSWlEPTB;MD6wNlkh|ryP MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN|E9N2F-
JVM-2 MV3DfZRwfG:6aXOgRZN{[Xl? MoPaO|IhcA>? MlTvSG1UVw>? M4XZUGlEPTB;MD6wNUDPxE1? Mn:3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN|EoRjJ3OEe4N|MyRC:jPh?=
Rec-1 NGnFUlVEgXSxdH;4bYMhSXO|YYm= M1WzW|czKGh? MlfXSG1UVw>? M4G0VmlEPTB;MD6wPFch|ryP MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN|E9N2F-
Z-138 NIWwblVEgXSxdH;4bYMhSXO|YYm= NHnPeWw4OiCq M3Kzb2ROW09? MnOzTWM2OD1yLkCxN{DPxE1? MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN|E9N2F-
H9 M4D1[mN6fG:2b4jpZ{BCe3OjeR?= NFjvfZY4OiCq NWPMbos6TE2VTx?= MkD3TWM2OD1yLk[g{txO MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN|E9N2F-
HH M4X4cWN6fG:2b4jpZ{BCe3OjeR?= NFvDR3c4OiCq MoThSG1UVw>? MXTJR|UxRTBwNzFOwG0> NIP5N4w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O|g{OzF:L3G+
DND41 M1vWb2N6fG:2b4jpZ{BCe3OjeR?= MVi3NkBp MlHJSG1UVw>? MUDJR|UxRTBwMTFOwG0> M4fseFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N|MyLz5{NUi3PFM{OTxxYU6=
CCL119 NGjqT4ZEgXSxdH;4bYMhSXO|YYm= Ml;wO|IhcA>? M3L0bWROW09? NXHzd5A1UUN3ME2wMlA3OiEQvF2= MlruQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN|EoRjJ3OEe4N|MyRC:jPh?=
J.Cam 1.6 M4LsNGN6fG:2b4jpZ{BCe3OjeR?= NV3tbXc5PzJiaB?= MWfEUXNQ NUXESlgxUUN3ME2wMlExPSEQvF2= M3rTXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N|MyLz5{NUi3PFM{OTxxYU6=
Sup-T1 NHfx[VlEgXSxdH;4bYMhSXO|YYm= NFzKVmM4OiCq M2C4O2ROW09? MkTRTWM2OD1{LkG0NkDPxE1? M3zIelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N|MyLz5{NUi3PFM{OTxxYU6=
Tib 152 NGWyXpdEgXSxdH;4bYMhSXO|YYm= NIi2bG84OiCq Mmi4SG1UVw>? M4PZWWlEPTB;MD64JO69VQ>? NUWzOVdDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O|g{OzFpPkK1PFc5OzNzPD;hQi=>
MCF7 M3\xUGZ2dmO2aX;uJGF{e2G7 MX[1JO69VQ>? MojmNlQhcA>? NXT1[IFRTE2VTx?= MV\JcoR2[2W|IFeyM20h[XK{ZYP0 MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh|NESwNUc,OjV6M{S0NFE9N2F-
MDA-MB-231 MkHjSpVv[3Srb36gRZN{[Xl? NIjrcG82KM7:TR?= MUKyOEBp NXvBWnBGTE2VTx?= MnXjTY5lfWOnczDHN{9OKGG{cnXzeC=> MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh|NESwNUc,OjV6M{S0NFE9N2F-
MCF7 M4f3eWZ2dmO2aX;uJGF{e2G7 M3K0PVUh|ryP NGfsUmUzPCCq NHvRUYxFVVOR NEDFU49F\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOS:FRFOy M{n1c|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MCF7 M1XtemZ2dmO2aX;uJGF{e2G7 NWD3XFVPPSEQvF2= NX7ZVmRkOjRiaB?= MoCwSG1UVw>? M4mzc2Rm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz M4DUcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MCF7 NUX0PIRmTnWwY4Tpc44hSXO|YYm= M4PTcFUh|ryP NIjoZ3EzPCCq M{S2dmROW09? MkTVSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIHP5Z4xqdiCEMR?= NV7G[oh4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MCF7 MmjRSpVv[3Srb36gRZN{[Xl? MnXYOUDPxE1? MUmyOEBp M1S4NWROW09? MXjJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEKxJHdi\jFxQ3nwNS=> NGnyOG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N|Q1ODF:L3G+
MCF7 M1\5S2Z2dmO2aX;uJGF{e2G7 M3jIXFUh|ryP M4jEPVI1KGh? MYnEUXNQ NHPUN3VKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFI4KEurcEG= NFjtVGo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N|Q1ODF:L3G+
MDA-MB-231 M136VmZ2dmO2aX;uJGF{e2G7 M1v4PFUh|ryP NX;USIt3OjRiaB?= NFTSZ2dFVVOR NVW2e254TGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=> MkXwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MDA-MB-231 NGr5XXpHfW6ldHnvckBCe3OjeR?= Mon4NUDPxE1? MVKyOEBp MknGSG1UVw>? M3HtZmlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh|NESwNUc,OjV6M{S0NFE9N2F-
MDA-MB-231 M4rBbGZ2dmO2aX;uJGF{e2G7 MnvsOUDPxE1? MWOyOEBp NHryRotFVVOR MnrySIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIHP5Z4xqdiCEMR?= MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh|NESwNUc,OjV6M{S0NFE9N2F-
MDA-MB-231 MVjGeY5kfGmxbjDBd5NigQ>? MYG1JO69VQ>? NHvsXlIzPCCq MlPuSG1UVw>? MmPVTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> M373S|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231 MUDGeY5kfGmxbjDBd5NigQ>? MYK1JO69VQ>? MVyyOEBp MXzEUXNQ NInNbHNKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFI4KEurcEG= MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh|NESwNUc,OjV6M{S0NFE9N2F-
MDA-MB-231 NHzZWlRHfW6ldHnvckBCe3OjeR?= NFvwTYE2KM7:TR?= NHHHWYszPCCq NUGxU4tDTE2VTx?= M1TmXWlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwOVM> MmGzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MCF7 M1ntXmFxd3C2b4Ppd{BCe3OjeR?= MknMOUDPxE1? NV\xXJlmOjRiaB?= M3;VcmROW09? MmXtTY5lfWOnczDhdI9xfG:2aXOg[IVifGh? NYnTW3ZLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MDA-MB-231 NILDRW5CeG:ydH;zbZMhSXO|YYm= NGj2U|Q2KM7:TR?= M2XKOVI1KGh? NI[5fodFVVOR NFzXTXRKdmS3Y3XzJIFxd3C2b4TpZ{Bl\WG2aB?= NYrYWHoxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MCF7 M1rWTGZ2dmO2aX;uJGF{e2G7 NGfK[HoyKM7:TR?= MkL0O|IhcA>? MWHEUXNQ NH;MXHJKdmS3Y3XzJIF2fG:yaHHnbYMh\GWjdHi= NHzZWIM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N|Q1ODF:L3G+
MDA-MB-231 MmnkSpVv[3Srb36gRZN{[Xl? Mnu2NUDPxE1? M3PJflczKGh? MYTEUXNQ NWrNSo5wUW6mdXPld{BifXSxcHjh[4lkKGSnYYTo MoHXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
U-2 OS MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXi1NEDPxE1? NX3OUWZrOjRiaB?= M1e0NWROW09? Mn\LTWM2OD1zNj62JO69VQ>? MkXFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5OUK4NVEoRjJ3N{myPFEyRC:jPh?=
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Rh18 NVfGRndMeUiWUzDhd5NigQ>? MV\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>? NW\KbFV5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC MWTxTHRUKGG|c3H5 MknUdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV2suVi2PQzDj[Yxtew>? MmflQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
TC32 NYPrbmxJeUiWUzDhd5NigQ>? M1ftZZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHREOzJiY3XscJM> M2C5NlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2 M4nZbpFJXFNiYYPzZZk> NITIVW9yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBU[W:|LUKgZ4VtdHN? Mn3GQIEhfGG{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; 

PubMed: 28073841     


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     


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     


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     


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     


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     


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     


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     


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]
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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]
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  • 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]
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  • 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 powder
in solvent
Synonyms N/A
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)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

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

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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 EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma|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|National Cancer Institute (NCI) 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 Active not 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

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

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID