Alisertib (MLN8237)

Catalog No.S1133

Alisertib (MLN8237) Chemical Structure

Molecular Weight(MW): 518.92

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

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Cited by 198 Publications

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Biological Activity

Description Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Phase 3.
Features First orally available inhibitor of Aurora A.
Targets
Aurora A [1]
(Cell-free assay)
1.2 nM
In vitro

MLN8237 shows >200-fold higher selectivity for Aurora A than the structurally related Aurora B with an IC50 of 396.5 nM, and does not have any significant activity against 205 other kinases. [1] MLN8237 (0.5 μM) treatment inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. MLN8237 significantly inhibits cell proliferation in multiple myeloma (MM) cell lines with IC50 values of 0.003-1.71 μM. MLN8237 displays more potent anti-proliferation activity against primary MM cells and MM cell lines in the presence of BM stroma cells, as well as IL-6 and IGF-1 than against MM cells alone. MLN8237 (0.5 μM) induces 2- to 6-fold increase in G2/M phase in primary MM cells and cell lines, as well as significant apoptosis and senescence, involving the up-regulation of p53, p21 and p27, as well as PARP, caspase 3, and caspase 9 cleavage. In addition, MLN8237 shows strong synergistic anti-MM effect with dexamethasone, as well as additive effect with doxorubicin and bortezomib. [2] MLN8237 (0.5 μM) treatment causes the inhibition of colony formation of FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, and induces a significant increase in the percentage of polyploid cells, and subsequently an increase in the percentage of cells in the sub-G1 phase, which can be further enhanced in combination with cisplatin (2.5 μM), involving the higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP as compared with a single-agent treatment. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 M{\Pe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPHNE42KM7:TR?= NILtSHI4OiCq NX70TYZYTE2VTx?= NHXP[IVKSzVyPUCuNFQh|ryP MV6yOlE{PjZ6NB?=
LS174T NFG2WnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYf4c|F1OC53IN88US=> NHjzbJc4OiCq MmfPSG1UVw>? NXT0UWQ4UUN3ME2wMlA2KM7:TR?= NY\rcG9jOjZzM{[2PFQ>
T84 NWrpT3lGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUPTVI1uOC53IN88US=> MlrJO|IhcA>? NXPhU4tHTE2VTx?= Mn73TWM2OD1yLkC5JO69VQ>? MoPkNlYyOzZ4OES=
LS180 M4rPOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETrNmoxNjVizszN NV7tdYN2PzJiaB?= M1rn[mROW09? MoP2TWM2OD1zIN88US=> NUO3W3RyOjZzM{[2PFQ>
SW948 Ml\WS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1jtWVAvPSEQvF2= NUTrPWdZPzJiaB?= NYnOeXFzTE2VTx?= MlvJTWM2OD1zIN88US=> NV6xO2dKOjZzM{[2PFQ>
HCT15 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlzHNE42KM7:TR?= MWe3NkBp NGLD[FVFVVOR M3XSeWlEPTB:MD60JO69VQ>? M2jh[FI3OTN4Nki0
DLD-1 NUWyb5RxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVnkdXVxOC53IN88US=> MYS3NkBp MmO2SG1UVw>? NXf3[JJTUUN3MEywMlgh|ryP MlW3NlYyOzZ4OES=
MIP-101 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFL0cGExNjVizszN M1GxN|czKGh? M{fhXmROW09? NITmNmhKSzVyPUGg{txO NXW4W5F{OjZzM{[2PFQ>
SNU1544 NI\SOoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYmwMlUh|ryP M2G5SVczKGh? NGjXO4RFVVOR MYXJR|UxRTFizszN MnPmNlYyOzZ4OES=
OCI-Ly10 MXjDfZRwfG:6aXOgRZN{[Xl? M4riRVczKGh? NEj4UHZFVVOR M2T1TmlEPTB;MD6wOVgh|ryP MXmyOVg4QDN|MR?=
SU-DHL2 NUjSTm5xS3m2b4TvfIlkKEG|c3H5 NYDmZ45EPzJiaB?= M1u2UWROW09? MlLTTWM2OD1yLkCxJO69VQ>? NVr6VFZzOjV6N{izN|E>
OCI-LY7 NWLRcnl{S3m2b4TvfIlkKEG|c3H5 NXuz[ZVtPzJiaB?= MnSySG1UVw>? NWm4W2lKUUN3ME2wMlA5OSEQvF2= NFjpbWUzPTh5OEOzNS=>
SU-DHL6 NU\ke5g3S3m2b4TvfIlkKEG|c3H5 NYfEdZN5PzJiaB?= M2n0XGROW09? M4LrVmlEPTB;MD60PFIh|ryP Mn\zNlU5Pzh|M{G=
Jeko-1 NWDEUVVVS3m2b4TvfIlkKEG|c3H5 NWnm[ZZyPzJiaB?= MkTCSG1UVw>? NV7HWIMxUUN3ME2wMlAzQSEQvF2= NHXkXmEzPTh5OEOzNS=>
JVM-2 M3vkWmN6fG:2b4jpZ{BCe3OjeR?= MVO3NkBp Ml\LSG1UVw>? MXHJR|UxRTBwMEGg{txO NXLzbIVFOjV6N{izN|E>
Rec-1 NULBTGMyS3m2b4TvfIlkKEG|c3H5 M2HqZVczKGh? MmDkSG1UVw>? Ml\ETWM2OD1yLkC4O{DPxE1? MWCyOVg4QDN|MR?=
Z-138 NGTvXnpEgXSxdH;4bYMhSXO|YYm= MVG3NkBp MkPxSG1UVw>? NVPTWWlqUUN3ME2wMlAyOyEQvF2= MXuyOVg4QDN|MR?=
H9 MUnDfZRwfG:6aXOgRZN{[Xl? MWC3NkBp NGG0b2lFVVOR MlHCTWM2OD1yLk[g{txO NV7RVZFOOjV6N{izN|E>
HH MYPDfZRwfG:6aXOgRZN{[Xl? M3Tx[|czKGh? NIDPR3lFVVOR M1jKTmlEPTB;MD63JO69VQ>? NH3iTJIzPTh5OEOzNS=>
DND41 NGXJelhEgXSxdH;4bYMhSXO|YYm= MofiO|IhcA>? M3n1d2ROW09? NU\5NI1ZUUN3ME2wMlEh|ryP MXGyOVg4QDN|MR?=
CCL119 M4TMdGN6fG:2b4jpZ{BCe3OjeR?= NHTBPWY4OiCq NW\oe4dwTE2VTx?= M3vWc2lEPTB;MD6wOlIh|ryP NUK5bpljOjV6N{izN|E>
J.Cam 1.6 NXjqPYxMS3m2b4TvfIlkKEG|c3H5 MYO3NkBp MkPXSG1UVw>? NFrnXJBKSzVyPUCuNVA2KM7:TR?= M3TyU|I2QDd6M{Ox
Sup-T1 MXjDfZRwfG:6aXOgRZN{[Xl? MkPPO|IhcA>? Mm\wSG1UVw>? NULme4ZFUUN3ME2yMlE1OiEQvF2= NVzMVo9uOjV6N{izN|E>
Tib 152 NVf3dIJkS3m2b4TvfIlkKEG|c3H5 MVq3NkBp M3zOT2ROW09? MYLJR|UxRTBwODFOwG0> NF7GenEzPTh5OEOzNS=>
MCF7 M3fpO2Z2dmO2aX;uJGF{e2G7 NIjZPWQ2KM7:TR?= MlOxNlQhcA>? NYD5ZVR3TE2VTx?= M33a[Wlv\HWlZYOgS|IwVSCjcoLld5Q> MoPvNlU5OzR2MEG=
MDA-MB-231 M{HDZWZ2dmO2aX;uJGF{e2G7 MkXUOUDPxE1? NH62dGszPCCq MmLPSG1UVw>? MlvRTY5lfWOnczDHN{9OKGG{cnXzeC=> MorJNlU5OzR2MEG=
MCF7 MWrGeY5kfGmxbjDBd5NigQ>? NXjkV2hpPSEQvF2= MXuyOEBp MkP0SG1UVw>? NGT5RVlF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOS:FRFOy MXKyOVg{PDRyMR?=
MCF7 Mli4SpVv[3Srb36gRZN{[Xl? Ml30OUDPxE1? NXzuRmt4OjRiaB?= MnGySG1UVw>? NUDmdmx[TGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzJ? NIHjS4szPTh|NESwNS=>
MCF7 NYLHTXpKTnWwY4Tpc44hSXO|YYm= MkfpOUDPxE1? NE[yd4EzPCCq MXPEUXNQ NF7iTFVF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gZ5lkdGmwIFKx NYf1d45FOjV6M{S0NFE>
MCF7 M1nTZWZ2dmO2aX;uJGF{e2G7 MX[1JO69VQ>? MXWyOEBp M1\KOGROW09? MnGwTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> Mn7LNlU5OzR2MEG=
MCF7 MWXGeY5kfGmxbjDBd5NigQ>? MUi1JO69VQ>? M2DqUlI1KGh? NYn1fIJ[TE2VTx?= MWPJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF? M2jIcFI2QDN2NECx
MDA-MB-231 NYPUT2N7TnWwY4Tpc44hSXO|YYm= MXW1JO69VQ>? NXnufnZrOjRiaB?= M1vV[mROW09? M4nxdGRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsyN0OGQ{K= M1LwVVI2QDN2NECx
MDA-MB-231 M{TqXGZ2dmO2aX;uJGF{e2G7 MmPrNUDPxE1? MoDqNlQhcA>? M1z0dWROW09? NIDIendKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOg>? NIjMZ|gzPTh|NESwNS=>
MDA-MB-231 MmjHSpVv[3Srb36gRZN{[Xl? NXz0PHZWPSEQvF2= NXHHS5h1OjRiaB?= MXzEUXNQ M{ixNWRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG= NUnWdllEOjV6M{S0NFE>
MDA-MB-231 NYLGem5pTnWwY4Tpc44hSXO|YYm= NYX2[HNCPSEQvF2= MW[yOEBp M3Pkd2ROW09? MnLXTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> NFnGSmEzPTh|NESwNS=>
MDA-MB-231 NHrYcIVHfW6ldHnvckBCe3OjeR?= M33WeFUh|ryP Mof4NlQhcA>? NIXOb5lFVVOR NGHLdINKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFI4KEurcEG= NXXOeIlbOjV6M{S0NFE>
MDA-MB-231 MnvoSpVv[3Srb36gRZN{[Xl? M2jwWlUh|ryP NF:3cYYzPCCq NULHVW9OTE2VTx?= NHvNNZdKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFU{ M3zW[FI2QDN2NECx
MCF7 NFXPS|lCeG:ydH;zbZMhSXO|YYm= NX3uVIViPSEQvF2= NYfDOmFVOjRiaB?= MnXySG1UVw>? MoX5TY5lfWOnczDhdI9xfG:2aXOg[IVifGh? Mme5NlU5OzR2MEG=
MDA-MB-231 MoLIRZBweHSxc3nzJGF{e2G7 NIjkVVc2KM7:TR?= M1zwc|I1KGh? M4PhPGROW09? NIfEdphKdmS3Y3XzJIFxd3C2b4TpZ{Bl\WG2aB?= NXjvToJpOjV6M{S0NFE>
MCF7 MV\GeY5kfGmxbjDBd5NigQ>? M1O3blEh|ryP NVzwV5F3PzJiaB?= MkPXSG1UVw>? MnXyTY5lfWOnczDheZRweGijZ3njJIRm[XSq MkLJNlU5OzR2MEG=
MDA-MB-231 MUTGeY5kfGmxbjDBd5NigQ>? M3TCeVEh|ryP NY\OSXZUPzJiaB?= MoLBSG1UVw>? NGjaUoZKdmS3Y3XzJIF2fG:yaHHnbYMh\GWjdHi= MVmyOVg{PDRyMR?=
U-2 OS NFPnTVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHroWWM2OCEQvF2= NU[5VlIxOjRiaB?= MVnEUXNQ NY\p[2FoUUN3ME2xOk43KM7:TR?= MofmNlU4QTJ6MUG=
MG-63 M{nESWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTFOVAh|ryP MnrXNlQhcA>? MULEUXNQ MWrJR|UxRTlwNTFOwG0> NH\JcHUzPTd7MkixNS=>
U-2 OS NX3xXVQySXCxcITvd4l{KEG|c3H5 M13JR|Uh|ryP NF;ZdVAzPCCq NFvBZmFFVVOR MonjTY5lfWOnczDhdI9xfG:2aXOgZ4VtdCCmZXH0bC=> Mnv4NlU4QTJ6MUG=
MG-63 NX65RpNESXCxcITvd4l{KEG|c3H5 NUfN[GdYPSEQvF2= MkThNlQhcA>? MWHEUXNQ M4XXfGlv\HWlZYOgZZBweHSxdHnjJINmdGxiZHXheIg> M3vDdVI2Pzl{OEGx
U-2 OS NH;YcoNHfW6ldHnvckBCe3OjeR?= NV36WIdIPSEQvF2= NWLaV5dJOjRiaB?= NYTodppZTE2VTx?= M3HQdXBzd22xdHXzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? NHXiS4IzPTd7MkixNS=>
MG-63 M1TaW2Z2dmO2aX;uJGF{e2G7 MWS1JO69VQ>? NWnUcIl1OjRiaB?= NG\lNXZFVVOR MoHEVJJwdW:2ZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp NV7v[XdlOjV5OUK4NVE>
PANC-1 NHHRVmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4ThUFUxKM7:TR?= NF7kcXMzPCCq Ml3USG1UVw>? M3;BZ2lEPTB;Nz6xJO69VQ>? MYeyOVY{OjJ{NR?=
BxPC-3 NX3MUGZqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUO4fI5jPTBizszN NGixNW0zPCCq NFXWV3VFVVOR MXHJR|UxRTZwODFOwG0> M{HJeVI2PjN{MkK1
PANC-1 MWfGeY5kfGmxbjDBd5NigQ>? NVfyWoVQPSEQvF2= MVKyOEBp M4\tfmROW09? MUjJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2IHnuJGczN01icHjhd4U> MWeyOVY{OjJ{NR?=
BxPC-3 M{LzUmZ2dmO2aX;uJGF{e2G7 MlX0OUDPxE1? M1m5c|I1KGh? M1niVWROW09? NFe0RZVKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V? M{HBVlI2PjN{MkK1
PANC-1 NYHaeZdpTnWwY4Tpc44hSXO|YYm= NETLTpU2KM7:TR?= NXe1bIhKOjRiaB?= Mof5SG1UVw>? M3nKRmlv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp M1\xcFI2PjN{MkK1
BxPC-3 MVrGeY5kfGmxbjDBd5NigQ>? MmHnOUDPxE1? MWGyOEBp M3jkcWROW09? MlPVTY5lfWOnczDheZRweGijZ3njJINmdGxiZHXheIg> NHfUOpkzPTZ|MkKyOS=>
SKOV3 MmHyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUPmWnY{OTByIN88US=> MkW1NlQhcA>? MmXISG1UVw>? NGjoT|JKSzVyPUKwMlQ5KM7:TR?= M{DIZlI2PjJ2N{Ww
OVCAR4 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2XGPFExOCEQvF2= MVGyOEBp MnHkSG1UVw>? M4DlR2lEPTB;MkKuNVMh|ryP NHvFWZQzPTZ{NEe1NC=>
SKOV3 MnzoSpVv[3Srb36gRZN{[Xl? NXTFfWhwPSEQvF2= NUL4fJdMPzJiaB?= NV3WfJpLTE2VTx?= MUPJcoR2[2W|IFeyM20h[XK{ZYP0 NH7p[3ozPTZ{NEe1NC=>
OVCAR4 MlPnSpVv[3Srb36gRZN{[Xl? Mnu2OUDPxE1? M1zyUVczKGh? MWXEUXNQ MYXJcoR2[2W|IFeyM20h[XK{ZYP0 MnTuNlU3OjR5NUC=
SKOV3 NVvIO3Q6SXCxcITvd4l{KEG|c3H5 NGTGe3g2KM7:TR?= M{PY[FI1KGh? M4TNdmROW09? MWDJcoR2[2W|IHHwc5B1d3Orcx?= NHHUUJgzPTZ{NEe1NC=>
OVCAR4 NYrDbVY3SXCxcITvd4l{KEG|c3H5 NUTw[INrPSEQvF2= NHLiOWozPCCq NELab5hFVVOR NYHxcWgzUW6mdXPld{BieG:ydH;zbZM> MXmyOVYzPDd3MB?=
AGS NHHEe25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3fpU|I2KM7:TR?= NGrYVGozPCCq MkfKSG1UVw>? NEe3RmFKSzVyPUG5MlA6KM7:TR?= M13RPVI2PjB7OUKz
NCI-N78 M2npRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2W4[|I2KM7:TR?= NFm0U|kzPCCq M3\yRmROW09? NIP4XYtKSzVyPUK2MlM{KM7:TR?= NWLMPWxwOjV4MEm5NlM>
AGS NWLQc5Z3SXCxcITvd4l{KEG|c3H5 MVO1JO69VQ>? MmHsNlQhcA>? NEnJb2NFVVOR MoPNTY5lfWOnczDhdI9xfG:|aYO= MUSyOVYxQTl{Mx?=
NCI-N78 NGTiUotCeG:ydH;zbZMhSXO|YYm= M4[4XVUh|ryP MVWyOEBp MmHhSG1UVw>? NWrF[GtuUW6mdXPld{BieG:ydH;zbZM> NIrpUXozPTZyOUmyNy=>
AGS MXHGeY5kfGmxbjDBd5NigQ>? NEfjdoQ2KM7:TR?= MnnjNlQhcA>? NVTI[|NiTE2VTx?= NFiwXG5KdmS3Y3XzJJRp\SCjdYTvdIhi\3l? Ml\xNlU3ODl7MkO=
NCI-N78 NIDPenVHfW6ldHnvckBCe3OjeR?= Ml3DOUDPxE1? MWWyOEBp M3PHSWROW09? Mn\uTY5lfWOnczD0bIUh[XW2b4DoZYd6 MWmyOVYxQTl{Mx?=
HSC-3 NVXod49pT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mmq2NUDPxE1? MWC0PEBp MXTJR|UxRTBwNUSg{txO MmDoNlU{PjZzNEO=
GB30 M2ri[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn;DNUDPxE1? M4PJfFch\A>? M{XSS2ROW09? MmTSTWM2OD1yLkCxNUDPxE1? NEHsO4gzPTFyNkSyPC=>
GB9 NV6zZ4hyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV\rZopwOSEQvF2= NYLVdHJuPyCm M1\tcWROW09? Moq5TWM2OD1yLkCyOEDPxE1? NV75VJkzOjVzME[0Nlg>
GB169 MnTVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PPbVEh|ryP NUP6[FZkPyCm NGOyTo5FVVOR NIXhTYJKSzVyPUCuNFMzKM7:TR?= MWCyOVExPjR{OB?=
T24 MYDGeY5kfGmxbjDBd5NigQ>? NYLI[nlWOSEQvF2= M3GxcVQ5KGh? MUfEUXNQ M4W5fWlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= NVT2UJBtOjN2MEO2N|M>
RT4 NXfvSGF5TnWwY4Tpc44hSXO|YYm= NF7iTJkyKM7:TR?= MV60PEBp M3\YWmROW09? M4XvOmlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= NW\5V2hzOjN2MEO2N|M>
UM-UC-3 NIT3e4RHfW6ldHnvckBCe3OjeR?= M170WFEh|ryP MmnmOFghcA>? MXvEUXNQ MkC0TY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?= NXm0R25UOjN2MEO2N|M>
T24 NGPUO5VCeG:ydH;zbZMhSXO|YYm= MYqzMlE3KM7:TR?= Ml7GPVYhcA>? M{\QOWROW09? M2XTc2lEPTB;MD6wN|A3KM7:TR?= NUHzenhOOjN2MEO2N|M>
RT4 Mme4RZBweHSxc3nzJGF{e2G7 MkPCN{4yPiEQvF2= NXO1dFlsQTZiaB?= MVzEUXNQ MkDWTWM2OD1yLkGxPVgh|ryP M1\pOFI{PDB|NkOz
UM-UC-3 MkHGRZBweHSxc3nzJGF{e2G7 MmDxN{4yPiEQvF2= M2rBUlk3KGh? NVnoOWQxTE2VTx?= MmW0TWM2OD1yLkC0OFkh|ryP NWDGTmRLOjN2MEO2N|M>
OVCAR-5 MnnZSpVv[3Srb36gRZN{[Xl? NUDBNmdVPTBibl2= M3jQfmlvcGmkaYTzJINmdGxibXnndoF1cW:w NGDqeXYzOzN|NEOyOy=>
SKOV3ip2 Mnr0SpVv[3Srb36gRZN{[Xl? MoDyOVAhdk1? MmPkTY5pcWKrdIOgZ4VtdCCvaXfyZZRqd25? MUeyN|M{PDN{Nx?=
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MOLT-4 NFvxb3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLyVWFGOTBizszN NVqyT3dRQTZiaB?= NHLuZ5RKSzVyPUCuNFI3KM7:TR?= MYKyNFExQDN|OB?=
CCRF-CEM MoroS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3TORlExKM7:TR?= M{LNRlk3KGh? NGPiT25KSzVyPUCuNFk1KM7:TR?= MlTFNlAyODh|M{i=
Kasumi-1 NU\DZpBQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHPCSIkyOCEQvF2= M{S2VVk3KGh? NEXzWWNKSzVyPUCuNVA{KM7:TR?= MkHjNlAyODh|M{i=
Karpas-299 M3XO[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NULEPGxHOTBizszN MYG5OkBp M2PoeGlEPTB;MD6wN|gh|ryP Mmi2NlAyODh|M{i=
Ramos-RA1 NF3i[Y9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWeyemV{OTBizszN M3LYVlk3KGh? NHzHO3RKSzVyPUCuNVI4KM7:TR?= MmTlNlAyODh|M{i=

... 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
  • Formulation: Formulated in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate
  • 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.
8mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 518.92
Formula

C27H20ClFN4O4

CAS No. 1028486-01-2
Storage powder
in solvent
Synonyms N/A

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
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*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
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    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):
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    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
NCT02812056 Withdrawn Drug: Alisertib|Drug: TAK-228 Malignant Neoplasms of Digestive Organs|Malignant Neoplasms of Female Genital Organs|Malignant Neoplasms of Lip Oral Cavity and Pharynx|Malignant Neoplasms of Male Genital Organs M.D. Anderson Cancer Center|Millennium Pharmaceuticals Inc. September 2016 Phase 1
NCT02719691 Recruiting Drug: Alisertib|Drug: MLN0128 Metastatic Breast Cancer|Solid Tumors University of Colorado Denver May 13 2016 Phase 1
NCT02367352 Terminated Drug: Alisertib|Drug: Paclitaxel Advanced Solid Tumors|Ovarian Cancer|Small Cell Lung Cancer Millennium Pharmaceuticals Inc.|Takeda March 19 2015 Phase 1

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.

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Frequently Asked Questions

  • Question 1:

    What is the suggested formulation of this compound for mouse injection(i.p.)?

  • Answer:

    It can be dissolved in 6% DMSO/50% PEG 300/5% Tween 80/ddH2O at 10 mg/ml as a clear solution.

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID