Alisertib (MLN8237)

Catalog No.S1133

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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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	MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NITNUmoxNjVizszN	NVmxS3hVPzJiaB?=	MonuSG1UVw>?	MnH0TWM2OD1yLkC0JO69VQ>?	M13HW\|I3OTN4Nki0
LS174T	NIX1TIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MVWwMlUh\|ryP	NEHxTZM4OiCq	M1Xqd2ROW09?	NEe5NlBKSzVyPUCuNFUh\|ryP	NFKxdIQzPjF\|Nk[4OC=>
T84	MonOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M3PlOVAvPSEQvF2=	NUHwVVF7PzJiaB?=	NIXRXJpFVVOR	NYLTfFExUUN3ME2wMlA6KM7:TR?=	NYD6Z5ZNOjZzM{[2PFQ>
LS180	NI\ETplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MljHNE42KM7:TR?=	MoTIO\|IhcA>?	MV;EUXNQ	NIm2b49KSzVyPUGg{txO	NXXaRo42OjZzM{[2PFQ>
SW948	MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Mk\uNE42KM7:TR?=	MlH5O\|IhcA>?	NVnQR\|ljTE2VTx?=	M2fQRmlEPTB;MTFOwG0>	NY\FZWhVOjZzM{[2PFQ>
HCT15	M{fZZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NHWyUGMxNjVizszN	MVG3NkBp	M{XmfmROW09?	NV\oTlVGUUN3MEywMlQh\|ryP	MXqyOlE{PjZ6NB?=
DLD-1	MnfzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NEDiPGYxNjVizszN	MYC3NkBp	M3fl[WROW09?	MoO5TWM2ODxyLkig{txO	MknYNlYyOzZ4OES=
MIP-101	MlS2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MlTnNE42KM7:TR?=	NIK3RpA4OiCq	MV3EUXNQ	MVLJR\|UxRTFizszN	M2fCVlI3OTN4Nki0
SNU1544	M2nUNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NX\iclM3OC53IN88US=>	NGC3fow4OiCq	MXHEUXNQ	Mo\nTWM2OD1zIN88US=>	MoPrNlYyOzZ4OES=
OCI-Ly10	NWHpb4V7S3m2b4TvfIlkKEG\|c3H5		M1ntc\|czKGh?	MVPEUXNQ	MlvyTWM2OD1yLkC1PEDPxE1?	M1PXblI2QDd6M{Ox
SU-DHL2	M{fnR2N6fG:2b4jpZ{BCe3OjeR?=		NFfIdXo4OiCq	MofXSG1UVw>?	MX\JR\|UxRTBwMEGg{txO	M2L6UFI2QDd6M{Ox
OCI-LY7	NUTsNFhmS3m2b4TvfIlkKEG\|c3H5		NFi5[4Y4OiCq	M3y1XmROW09?	NIT2c\|ZKSzVyPUCuNFgyKM7:TR?=	NFTp[IIzPTh5OEOzNS=>
SU-DHL6	NUTicXp5S3m2b4TvfIlkKEG\|c3H5		MVi3NkBp	NF21WplFVVOR	NX2zW3k4UUN3ME2wMlQ5OiEQvF2=	MoPkNlU5Pzh\|M{G=
Jeko-1	NWHzNIF4S3m2b4TvfIlkKEG\|c3H5		NX;obWp6PzJiaB?=	M2TE[GROW09?	MWjJR\|UxRTBwMEK5JO69VQ>?	NXLtNFJYOjV6N{izN\|E>
JVM-2	MlPSR5l1d3SxeHnjJGF{e2G7		NX7jOoNYPzJiaB?=	MkLGSG1UVw>?	NEHiWVZKSzVyPUCuNFEh\|ryP	NX3PNYhROjV6N{izN\|E>
Rec-1	M{fIVmN6fG:2b4jpZ{BCe3OjeR?=		MYO3NkBp	NWDaVlJmTE2VTx?=	MXfJR\|UxRTBwMEi3JO69VQ>?	NVHh[ms3OjV6N{izN\|E>
Z-138	NFzPdoZEgXSxdH;4bYMhSXO\|YYm=		MkjIO\|IhcA>?	M1eyV2ROW09?	NFHJe4pKSzVyPUCuNFE{KM7:TR?=	M2rrXlI2QDd6M{Ox
H9	NX[yR5lPS3m2b4TvfIlkKEG\|c3H5		Mof4O\|IhcA>?	MnjqSG1UVw>?	NYTsVGpJUUN3ME2wMlYh\|ryP	MnjaNlU5Pzh\|M{G=
HH	NY\ndllMS3m2b4TvfIlkKEG\|c3H5		NUPxUnRlPzJiaB?=	MXvEUXNQ	NV3MdVJoUUN3ME2wMlch\|ryP	Ml7INlU5Pzh\|M{G=
DND41	M1PTOmN6fG:2b4jpZ{BCe3OjeR?=		Mn7oO\|IhcA>?	NInBcWJFVVOR	M1zKZWlEPTB;MD6xJO69VQ>?	M17weVI2QDd6M{Ox
CCL119	MXXDfZRwfG:6aXOgRZN{[Xl?		MV63NkBp	NYrsVoFRTE2VTx?=	NGXVcppKSzVyPUCuNFYzKM7:TR?=	MmTKNlU5Pzh\|M{G=
J.Cam 1.6	NXjTOW83S3m2b4TvfIlkKEG\|c3H5		NYDjfWtyPzJiaB?=	MUDEUXNQ	NFPYW45KSzVyPUCuNVA2KM7:TR?=	NIPrRnEzPTh5OEOzNS=>
Sup-T1	M3uzTGN6fG:2b4jpZ{BCe3OjeR?=		NWjhOlhvPzJiaB?=	Ml7vSG1UVw>?	MmXTTWM2OD1{LkG0NkDPxE1?	NIfON4gzPTh5OEOzNS=>
Tib 152	NYL0VZVuS3m2b4TvfIlkKEG\|c3H5		NIG3cnM4OiCq	NUHaVox3TE2VTx?=	MXfJR\|UxRTBwODFOwG0>	MWiyOVg4QDN\|MR?=
MCF7	Mor0SpVv[3Srb36gRZN{[Xl?	NUHOfnUyPSEQvF2=	NH\Rb4ozPCCq	MXzEUXNQ	MXPJcoR2[2W\|IFeyM20h[XK{ZYP0	MXGyOVg{PDRyMR?=
MDA-MB-231	M{HRRWZ2dmO2aX;uJGF{e2G7	NYfQS\|J3PSEQvF2=	M1XqbFI1KGh?	M3jGPGROW09?	M{nmOmlv\HWlZYOgS\|MwVSCjcoLld5Q>	MkDTNlU5OzR2MEG=
MCF7	NXvscYFTTnWwY4Tpc44hSXO\|YYm=	NWfaPYxYPSEQvF2=	M{jiR\|I1KGh?	NVnwWnFPTE2VTx?=	NHXSSpFF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOS:FRFOy	MVyyOVg{PDRyMR?=
MCF7	NFPGTYJHfW6ldHnvckBCe3OjeR?=	NV7NR3ZjPSEQvF2=	NHfUWJgzPCCq	NIHs[5RFVVOR	NF;NfpBF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOg>?	NEfyWJYzPTh\|NESwNS=>
MCF7	M1;TVGZ2dmO2aX;uJGF{e2G7	NGPyUYQ2KM7:TR?=	NXjWZVVFOjRiaB?=	NFfnOGxFVVOR	M3fJcmRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG=	Mof3NlU5OzR2MEG=
MCF7	MWTGeY5kfGmxbjDBd5NigQ>?	NWP4TZZsPSEQvF2=	NYSxZnNLOjRiaB?=	NEf3N3pFVVOR	NIe4PJVKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFIyKFejZkGvR4lxOQ>?	NHTkUWQzPTh\|NESwNS=>
MCF7	MXvGeY5kfGmxbjDBd5NigQ>?	NVjoXHZKPSEQvF2=	NFTUSIMzPCCq	MWrEUXNQ	MULJcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF?	Mo\ZNlU5OzR2MEG=
MDA-MB-231	NI\yZ\|BHfW6ldHnvckBCe3OjeR?=	MYe1JO69VQ>?	MXOyOEBp	MWjEUXNQ	MmfNSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET\|EwS0SFMh?=	NIX6fFEzPTh\|NESwNS=>
MDA-MB-231	NFL6SZhHfW6ldHnvckBCe3OjeR?=	MoLxNUDPxE1?	MUGyOEBp	NU\mfJQ4TE2VTx?=	MWXJcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNi=>	MmnRNlU5OzR2MEG=
MDA-MB-231	MoexSpVv[3Srb36gRZN{[Xl?	MojUOUDPxE1?	NWTEWW9GOjRiaB?=	MlnySG1UVw>?	MXPE[YNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiY4njcIlvKEJz	MmLhNlU5OzR2MEG=
MDA-MB-231	M{jkTGZ2dmO2aX;uJGF{e2G7	MnrWOUDPxE1?	NXfqNpNjOjRiaB?=	NU\VVVhWTE2VTx?=	MX7JcoNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEKxJHdi\jFxQ3nwNS=>	M3W3Z\|I2QDN2NECx
MDA-MB-231	NFW3fpNHfW6ldHnvckBCe3OjeR?=	MXe1JO69VQ>?	MlL2NlQhcA>?	MYHEUXNQ	M4jKO2lv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?=	M330dVI2QDN2NECx
MDA-MB-231	NYnKVZdGTnWwY4Tpc44hSXO\|YYm=	NFn3Nlc2KM7:TR?=	MUeyOEBp	MmHKSG1UVw>?	NGr5TWhKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFU{	NYnXOVVKOjV6M{S0NFE>
MCF7	Mn:1RZBweHSxc3nzJGF{e2G7	NHf0eoU2KM7:TR?=	M3zJXlI1KGh?	MYnEUXNQ	M{LtXmlv\HWlZYOgZZBweHSxdHnjJIRm[XSq	M3TSV\|I2QDN2NECx
MDA-MB-231	M{iwNmFxd3C2b4Ppd{BCe3OjeR?=	NH;MUHo2KM7:TR?=	NYj4XI9lOjRiaB?=	Mn3uSG1UVw>?	NF2zWHhKdmS3Y3XzJIFxd3C2b4TpZ{Bl\WG2aB?=	MmHoNlU5OzR2MEG=
MCF7	NGjt[lJHfW6ldHnvckBCe3OjeR?=	MnXVNUDPxE1?	M33lU\|czKGh?	NF3zTFBFVVOR	MVfJcoR2[2W\|IHH1eI9xcGGpaXOg[IVifGh?	M3jwb\|I2QDN2NECx
MDA-MB-231	NGnWZZhHfW6ldHnvckBCe3OjeR?=	M{\sUlEh\|ryP	MYi3NkBp	MVrEUXNQ	NUDkc3pvUW6mdXPld{BifXSxcHjh[4lkKGSnYYTo	Ml:yNlU5OzR2MEG=
U-2 OS	NUG0bpI1T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NXfiT2dLPTBizszN	NYrEepl2OjRiaB?=	MYDEUXNQ	M1\SPGlEPTB;MU[uOkDPxE1?	MlTYNlU4QTJ6MUG=
MG-63	MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4r2elUxKM7:TR?=	MUGyOEBp	M4\EdGROW09?	M1m2NGlEPTB;OT61JO69VQ>?	M{f2NlI2Pzl{OEGx
U-2 OS	NYHrOmQ4SXCxcITvd4l{KEG\|c3H5	NGDyXnQ2KM7:TR?=	NHvDTYEzPCCq	NXPDR4NpTE2VTx?=	NFP0fIFKdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRp	NEDmR5MzPTd7MkixNS=>
MG-63	MXvBdI9xfG:\|aYOgRZN{[Xl?	MWm1JO69VQ>?	M3\oWVI1KGh?	MV;EUXNQ	MUPJcoR2[2W\|IHHwc5B1d3SrYzDj[YxtKGSnYYTo	MVOyOVc6OjhzMR?=
U-2 OS	M4rzNmZ2dmO2aX;uJGF{e2G7	NFiyPGc2KM7:TR?=	NEew[4czPCCq	MXHEUXNQ	MnXGVJJwdW:2ZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp	MmTsNlU4QTJ6MUG=
MG-63	MXTGeY5kfGmxbjDBd5NigQ>?	MXu1JO69VQ>?	MYOyOEBp	NYjTbnZITE2VTx?=	NFHsbpJRem:vb4Tld{BifXSxcHjh[4lkKGOnbHyg[IVifGh?	NIe4XoEzPTd7MkixNS=>
PANC-1	MnvwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NEjxRm82OCEQvF2=	MYCyOEBp	MVjEUXNQ	M2jMNGlEPTB;Nz6xJO69VQ>?	M1SwVFI2PjN{MkK1
BxPC-3	NWrYU3lIT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M1Xmb\|UxKM7:TR?=	MXmyOEBp	MWTEUXNQ	MULJR\|UxRTZwODFOwG0>	MViyOVY{OjJ{NR?=
PANC-1	MW\GeY5kfGmxbjDBd5NigQ>?	NXXvRWlSPSEQvF2=	NH\FWXQzPCCq	NWmz[5JKTE2VTx?=	NG\ITWZKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V?	NUHWSVROOjV4M{KyNlU>
BxPC-3	M4L0fWZ2dmO2aX;uJGF{e2G7	MkDZOUDPxE1?	NV\pTlg1OjRiaB?=	NFu3PHNFVVOR	M1KzeGlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgbY4hTzJxTTDwbIF{\Q>?	MYKyOVY{OjJ{NR?=
PANC-1	M2izbGZ2dmO2aX;uJGF{e2G7	MYW1JO69VQ>?	NWL2c5BwOjRiaB?=	M4\ZZWROW09?	NEfYUlVKdmS3Y3XzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>?	M1PGVVI2PjN{MkK1
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SK-N-BE-1	M2PLV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MlnaNVAh\|ryP	MWm5OkBp	M{m0OGROW09?	NXXk[nJpUUN3ME2wMlAzQCEQvF2=	NGnMUnIzOTR2OEW5NS=>
SK-N-BE-2	NVvmbHNoT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NIPkSW4yOCEQvF2=	NHOyZ4I6PiCq	M33lNWROW09?	MXHJR\|UxRTBwMEO2JO69VQ>?	M3HWWlIyPDR6NUmx
SMS-KAN	NGfqW\|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NEHNXYwyOCEQvF2=	Mo[wPVYhcA>?	NFPjOVRFVVOR	MoD3TWM2OD1yLkCzOEDPxE1?	M3z0UFIyPDR6NUmx
SMS-KANR	M4fzcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MkTCNVAh\|ryP	M4rCcFk3KGh?	MmPaSG1UVw>?	NFHKdYNKSzVyPUCuNFI3KM7:TR?=	MmTYNlE1PDh3OUG=
SMS-KCN	NGPI[nFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NYXUSWlqOTBizszN	NF24SIY6PiCq	MVnEUXNQ	NITlNGNKSzVyPUCuNFE6KM7:TR?=	NIPFOFYzOTR2OEW5NS=>
SMS-KCNR	MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MlHMNVAh\|ryP	M334UVk3KGh?	NETxVZBFVVOR	M1i4TmlEPTB;MD6wNVAh\|ryP	M1jt[VIyPDR6NUmx
SMS-LHN	NHfoXmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MnLDNVAh\|ryP	NVXj[nRHQTZiaB?=	MYnEUXNQ	NUfUWpU2UUN3ME2wMlA{OiEQvF2=	M2mzXVIyPDR6NUmx
SMS-MSN	M1fTSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NX[yNJEzOTBizszN	NF;DTZA6PiCq	NVTZT3NRTE2VTx?=	MYHJR\|UxRTBwMEKyJO69VQ>?	NVjSXJBKOjF2NEi1PVE>
SMS-SAN	NULNO5JtT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NXziRYlROTBizszN	MUK5OkBp	NXvDZoRETE2VTx?=	M{\qXWlEPTB;MD6wNlAh\|ryP	MnTsNlE1PDh3OUG=
Granta-4	M1rCOWN6fG:2b4jpZ{BCe3OjeR?=	NEj5[\|cyOCEQvF2=	M3vWU\|ch\A>?		MoTZTWM2OD1yLkC0NEDPxE1?	MlXjNlEzQTF6Nke=
DB	MX3DfZRwfG:6aXOgRZN{[Xl?	MXOxNEDPxE1?	MoXZO{Bl		Mnr0TWM2OD1yLkC0NkDPxE1?	M1zVdFIyOjlzOE[3
RL	M37NT2N6fG:2b4jpZ{BCe3OjeR?=	Ml;aNVAh\|ryP	MnTiO{Bl		NGfQOnVKSzVyPUCuNFE2KM7:TR?=	NYDxcVhPOjF{OUG4Olc>
K562	MmT4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M4rwNVExKM7:TR?=	M4S0UVk3KGh?		NXjYd2NDUUN3ME2wMlA5PyEQvF2=	Moj1NlExQTF4M{O=
LAMA-84	NEjvRXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MUmxNEDPxE1?	M3Ls[\|k3KGh?		MmTpTWM2OD1yLkC1O{DPxE1?	NWrWNoF5OjFyOUG2N\|M>
MM15	MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MWm0JO69VQ>?	Mn6yO\|IhcA>?	Mn7GSG1UVw>?	NYDC[WlwUUN3ME2wMlE{KM7:TR?=	NGfa[oEzODN6Mki0OC=>
OPM1	M4fXUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M2XDPFQh\|ryP	NYjIZnlyPzJiaB?=	NHnHclBFVVOR	MoG0TWM2OD1yLkCzJO69VQ>?	MXqyNFM5Ojh2NB?=
RPM1	M2HBfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NW\qVoJZPCEQvF2=	NFywbIw4OiCq	MXjEUXNQ	NHe5O\|VKSzVyPUGwMlMzKM7:TR?=	NFn0NVUzODN6Mki0OC=>
INA6	NFK1bZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NEHwTWU1KM7:TR?=	NXP2XohIPzJiaB?=	M4nYNGROW09?	MVTJR\|UxRTBwMECyJO69VQ>?	M372XVIxOzh{OES0
OPM2	NH7sNnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MWG0JO69VQ>?	MnXJO\|IhcA>?	M4PzTmROW09?	M1vpZWlEPTB;ND6zO{DPxE1?	MUCyNFM5Ojh2NB?=
MM1R	MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NXTmZWdpPCEQvF2=	NFjuSG84OiCq	Mo\jSG1UVw>?	Mk\UTWM2OD1zLk[4JO69VQ>?	MVOyNFM5Ojh2NB?=
DOX40	MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Mnz2OEDPxE1?	M373S\|czKGh?	M2jaO2ROW09?	MV3JR\|UxRTVwNEig{txO	M4HQelIxOzh{OES0
LR5	MnK1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NHWzPVQ1KM7:TR?=	MoLoO\|IhcA>?	NVLpVIZSTE2VTx?=	NEDFWo5KSzVyPUKuOVMh\|ryP	MXyyNFM5Ojh2NB?=
U266	NWrmU3ZpT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NX2xS2lYPCEQvF2=	NGjk[Gw4OiCq	NVu5bpdWTE2VTx?=	NHy0WoxKSzVyPUGuOFMh\|ryP	NX7JNYlvOjB\|OEK4OFQ>
RD	NFTldXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MUSxNEDPxE1?	M{K5R\|k3KGh?		MVjJR\|UxRTBwMkK4JO69VQ>?	MVKyNFExQDN\|OB?=
Rh41	Moq0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MWWxNEDPxE1?	M3rib\|k3KGh?		M2PwRmlEPTB;MD6wPVAh\|ryP	MnzxNlAyODh\|M{i=
Rh30	NWnufpl{T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MVKxNEDPxE1?	NIrDXZU6PiCq		NGLPR4JKSzVyPUCuNlMxKM7:TR?=	Mn65NlAyODh\|M{i=
BT-12	M134O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MVmxNEDPxE1?	NWPrTIgxQTZiaB?=		M3\oOWlEPTB;MD6wOlAh\|ryP	MX:yNFExQDN\|OB?=
CHLA-266	MmnzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MnvNNVAh\|ryP	NFSyN\|g6PiCq		M4fNXGlEPTB;MD6wO\|Ih\|ryP	NYLlUXpNOjBzMEizN\|g>
TC-71	MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MUixNEDPxE1?	NVP0dml[QTZiaB?=		MkjXTWM2OD1yLkGwNkDPxE1?	NVy5O3VROjBzMEizN\|g>
SJ-GBM2	MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NGK3UYUyOCEQvF2=	MX65OkBp		MmDwTWM2OD1yLkC1NEDPxE1?	MUCyNFExQDN\|OB?=
NALM-6	Mon1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MVexNEDPxE1?	NHzxem46PiCq		NH71XItKSzVyPUCuNFYzKM7:TR?=	MoL6NlAyODh\|M{i=
COG-LL-317	NV;ZO4xoT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MmHCNVAh\|ryP	MVm5OkBp		MnvDTWM2OD1yLkC0O{DPxE1?	NGPJWXgzODFyOEOzPC=>
RS4-11	MlXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NVjlPGlYOTBizszN	M4nRS\|k3KGh?		NGftNohKSzVyPUCuNFE5KM7:TR?=	MkThNlAyODh\|M{i=
MOLT-4	M33sfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NVju[od5OTBizszN	NHywUW86PiCq		NUnx[4VMUUN3ME2wMlAzPiEQvF2=	MU[yNFExQDN\|OB?=
CCRF-CEM	MnKzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MWexNEDPxE1?	MWe5OkBp		M2m1SWlEPTB;MD6wPVQh\|ryP	NEXqSYkzODFyOEOzPC=>
Kasumi-1	NIq3U2xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYCxNEDPxE1?	Mo\CPVYhcA>?		M1LIWWlEPTB;MD6xNFMh\|ryP	M{LFXFIxOTB6M{O4
Karpas-299	MmfBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NFuwWYkyOCEQvF2=	NUPjWFlVQTZiaB?=		MVjJR\|UxRTBwMEO4JO69VQ>?	MnnJNlAyODh\|M{i=
Ramos-RA1	NEHPNnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MXGxNEDPxE1?	NX\GN4F5QTZiaB?=		NELLRVBKSzVyPUCuNVI4KM7:TR?=	Ml\rNlAyODh\|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 Clin Cancer Res 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 Cell 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 Mol Cells 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 Drug Des Devel Ther 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 FASEB J 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 Oncogene 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 Oncotarget 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 Blood 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]	+ Expand 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]	+ Expand 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]	+ Expand 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)

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.	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 Download Alisertib (MLN8237) SDF

Molecular Weight	518.92
Formula	C₂₇H₂₀ClFN₄O₄
CAS No.	1028486-01-2
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A

Bio Calculators

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-03-27)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02860000	Recruiting	Estrogen Receptor Status\|HER2/Neu Negative\|Invasive Breast Carcinoma\|Postmenopausal\|Stage III Breast Cancer\|Stage IIIA Breast Cancer\|Stage IIIB Breast Cancer\|Stage IIIC Breast Cancer\|Stage IV Breast Cancer	Mayo Clinic\|National Cancer Institute (NCI)	July 6 2017	Phase 2
NCT02860000	Recruiting	Estrogen Receptor Status\|HER2/Neu Negative\|Invasive Breast Carcinoma\|Postmenopausal\|Stage III Breast Cancer\|Stage IIIA Breast Cancer\|Stage IIIB Breast Cancer\|Stage IIIC Breast Cancer\|Stage IV Breast Cancer	Mayo Clinic\|National Cancer Institute (NCI)	July 6 2017	Phase 2
NCT02700022	Terminated	Diffuse Large B-cell Lymphoma\|Follicular Lymphoma\|Burkitt Lymphoma	UNC Lineberger Comprehensive Cancer Center\|Millennium Pharmaceuticals Inc.	October 2016	Phase 1
NCT02700022	Terminated	Diffuse Large B-cell Lymphoma\|Follicular Lymphoma\|Burkitt Lymphoma	UNC Lineberger Comprehensive Cancer Center\|Millennium Pharmaceuticals Inc.	October 2016	Phase 1
NCT02812056	Withdrawn	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
NCT02812056	Withdrawn	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

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.

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

Pan Aurora Kinase Inhibitor

Danusertib (PHA-739358) : Pan-Aurora kinase inhibitor, Aurora A/B/C, IC50=13 nM/79 nM/61 nM.
Pan Aurora Kinase Inhibitor

SNS-314 Mesylate : Pan-Aurora kinase inhibitor, Aurora A/B/C, IC50=9 nM/31 nM/3 nM.
Most Potent Aurora Kinase Inhibitor

MK-5108 (VX-689) : Aurora A, IC50=0.064 nM.
Aurora Kinase Inhibitor in Clinical Trial

VX-680 (Tozasertib, MK-0457) : Phase II for Advanced Non-Small Cell Lung Cancer (NSCLC).
Classic Aurora Kinase Inhibitor

Hesperadin : Potently inhibits Aurora B with IC50 of 250 nM.

Related Aurora Kinase Products5

Ro-3306 ^New

RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with K_i of 20 nM, >15-fold selectivity against a diverse panel of human kinases.
CCG-1423 ^New

CCG-1423 is a specific RhoA pathway inhibitor, which inhibits SRF-mediated transcription.
ML141 ^New

ML141 (CID-2950007), is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with IC50 of 200 nM and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7).
Barasertib (AZD1152-HQPA|AZD2811)

Barasertib (AZD1152-HQPA) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1.
Tozasertib (VX-680, MK-0457)

Tozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with K_i_app of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. Phase 2.
Danusertib (PHA-739358)

Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Phase 2.
ZM 447439

ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.

Features:An Aurora selective ATP-competitive inhibitor.
MLN8054

MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM in Sf9 insect cell. It is more than 40-fold selective for Aurora A than Aurora B. Phase 1.
MK-5108 (VX-689)

MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. Phase 1.
Aurora A Inhibitor I (TC-S 7010)

Aurora A Inhibitor I 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.

Features:Aurora A Inhibitor I is a novel, potent, and selective inhibitor to Aurora A.

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Alisertib (MLN8237)

Cited by 68 Publications

Purity & Quality Control

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Biological Activity

Protocol

References

Solubility (25°C)

Chemical Information Download Alisertib (MLN8237) SDF

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Molecular Weight Calculator

Total Molecular Weight: g/mol

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-03-27)

Tech Support

Frequently Asked Questions

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

Related Aurora Kinase Products5

Choose Your Country or Region

By Signaling Pathways

By product type

Alisertib (MLN8237)

Cited by 68 Publications

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Biological Activity

Protocol

References

Solubility (25°C)

Chemical Information Download Alisertib (MLN8237) SDF

Bio Calculators

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Dilution Calculator

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

The Serial Dilution Calculator Equation

Serial Dilutions

Computed Result

Molecular Weight Calculator

Total Molecular Weight: g/mol

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

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

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-03-27)

Tech Support

Frequently Asked Questions

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

Related Aurora Kinase Products5

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