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 49 Publications

12 Customer Reviews

  • Inhibition of Aurka kinase activity by MLN8237 impairs expression of pluripotency genes in CCE cells as measured by qRT-PCR. All values shown are mean ?SEM for n=3. The level of phosphorylated H3(S10) (p-H3(S10)), an Aurka phosphorylation target site, is decreased in MLN8237-treated samples.

    Cell Stem Cell 2012 11, 179-94. Alisertib (MLN8237) purchased from Selleck.

    Recruitment of clathrin to the mitotic spindle is controlled by phosphorylation of TACC3 by Aurora-A kinase. Representative micrographs of HEK293 cells incubated with 0.3 μM MLN8237 for 40 min. Cells were fixed and stained as indicated.

    EMBO J 2012 30, 906-19. Alisertib (MLN8237) purchased from Selleck.

  • Tissue levels of 53BP1, a-tubulin, IkB-a and IL-6 in an Hs294T xenograft treated with MLN8237 or vehicle control were visualized by immunofluorescence co-staining with DAPI. Representative micrographs are shown from triplicate experiments.

    EMBO Mol Med 2013 5(1), 149-66. Alisertib (MLN8237) purchased from Selleck.

    NUSAP mitotic phosphorylation at Ser 240 correlates with Aurora A activity. Protein samples of FLAG-NUSAP immunoprecipitated from I, M and MtMLN or with MtZM were analysed using LC-MS/MS, focusing on the predicted phosphorylated residue Ser 240. The histograms (A, B) show the calculated ratios based on peptides carrying the phosphorylated Ser 240 compared with all matched peptides containing this residue.

     

     

    EMBO reports 2010 11, 977-984. Alisertib (MLN8237) purchased from Selleck.

  • Aurora A inhibition rescues the PPP6C depletion phenotype. (A) HeLa cells transfected for 48 h with control and PPP6C si08 duplexes were treated with 10 or 20 nM MLN8237 or a solvent control for 15 min before lysis in phosphatase inhibitor containing buffer or fixation. Total lysates were analyzed by Western blotting. The red and black lines indicate the hosphorylated and nonphosphorylated forms of Aurora A. Fixed cells were stained using DAPI to detect DNA and antibodies to α-tubulin and Aurora A pT288. The intensity of pT288 staining was integrated using ImageJ over the spindle region defined by TPX2 staining and is plotted in the bar graph ( n = 4). Arrowheads indicate micronuclei. Bar, 5 µm. (B) HeLa cells transfected for 48 h with control and PPP6C si08 duplexes were treated with 10 nM MLN8237 or a solvent control for 24 h before fixation and staining with DAPI to detect DNA.

    J Cell Biol 2010 191, 1315-32. Alisertib (MLN8237) purchased from Selleck.

    D) Pharmacological inhibition of AURKA using alisertib led to downregulation of p-EIF4E (S209) and c-MYC proteins in FLO-1 and SK-GT-4 resistant cells, with or without RAD001 treatment.

    Clin Cancer Res, 2017, 23(14):3756-3768. Alisertib (MLN8237) purchased from Selleck.

  • Eg5 inhibition counteracts the induction of spindle pole fragmentation by Aurora-A inactivation. The protocol to inhibit Aurora-A by MLN8237 in cells progressing towards mitosis is depicted (time intervals not represented to scale). Control cultures were treated with solvent (DMSO) in the same time window. When indicated, MON was added 1 hour before harvesting. Note the absence of active phosphorylated (pThr288) Aurora-A (in red in IF panels) in cells treated with MLN8237. Upper histograms represent the percentage of all spindle and MT abnormalities in control and MLN8237-treated cultures (200 counted PM/M per condition in 2 experiments); the grey fraction of the histograms represents mitoses with spindle extrapoles, while other defects (monopolar or disorganised spindles, few and short MTs) are in white. Lower histograms and IF panels show that concomitant Eg5 inhibition by MON prevents MLN8237-induced spindle pole fragmentation (note the failure of centrosome migration reflecting Eg5 inactivation in lower IF panels). 200 PM/M per condition were counted in 2 experiments. Error bars represent s.d. **: p < 0.001, χ2 test. Red asterisks indicate significant differences with respect to DMSO controls, and black asterisks significant differences between Aurora-Ai mitoses with active or inactive Eg5. Scale bar: 10 μm

    Mol Cancer 2011 10, 131. Alisertib (MLN8237) purchased from Selleck.

    Alisertib inhibits AURKA and AURKB in a concentration-dependent manner. (a) Alisertib induces G 2 /M delay or genome reduplication. HeLa cells were exposed to buffer or the indicated concentrations of Alisertib. After 24 h, the cells were harvested and analyzed with flow cytometry. The positions of 2N, 4N and 8N DNA contents are indicated. (b) Alisertib delays mitotic exit or induces slippage. HeLa cells stably expressing histone H2B-GFP were exposed to buffer or the indicated concentrations of Alisertib. Individual cells were then tracked for 24 h with time-lapse microscopy. Each horizontal bar represents one cell (n ¼ 50). Key: light gray ¼ interphase; black ¼ mitosis (from DNA condensation to anaphase or mitotic slippage); dark gray ¼ interphase after mitotic slippage; truncated bars ¼ cell death. (c) Different concentrations of Alisertib are involved in delaying mitotic exit and inducing slippage. Live-cell imaging of cells treated with Alisertib was described in panel (b). The duration of mitosis (mean±90% confidence interval) and the percentage of cells that underwent mitotic slippage during the imaging period was quantified. (d) Alisertib promotes apoptosis in a concentration-dependent manner. HeLa cells were incubated with the indicated concentrations of Alisertib for 48 h. The cells were then harvested and analyzed with flow cytometry. (e) Concentration-dependent cytotoxicity of Alisertib. HeLa cells were cultured in the presence of the indicated concentrations of Alisertib for 48 h. The number of live and dead cells was analyzed with trypan blue exclusion assay. (f) Concentration-dependent suppression of long-term survival by Alisertib. HeLa cells were seeded on 60-mm culture plates and grown in the presence of 250 n M or 1 m M of Alisertib. After 24 h, the cells were washed gently and propagated in normal medium for another 10–12 days. Colonies were fixed and stained with crystal violet solution (examples of the plates are shown). Average±s.d. from three independent experiments. (g) Both AURKA and AURKB are inhibited by Alisertib.Mitotic HeLa cells were obtained by exposure to nocodazole for 16 h followed by mechanical shake off. The cells were incubated with the indicated concentrations of Alisertib for 2 h. Lysates were then prepared and activated phospho-AURKAThr288 and AURKBThr232were detected with immunoblotting. The asterisk indicates the position of an AURKB-like protein (the same throughout this study). Uniform loading was confirmed by immunoblotting for actin. In this assay, nocodazole and MG132 (a proteasome inhibitor) were added to prevent the cells from exiting mitosis. Accordingly, the total AURKA and AURKB levels remained constant throughout the experiment. (h) Alisertib prevents activation of AURKA and AURKB. HeLa cells were incubated with the indicated concentrations of Alisertib for 8 h. Nocodazole was then added for another 6 h to trap cells that entered mitosis. Lysates were prepared and analyzed with immunoblotting. Actin analysis was included to assess loading and transfer.

    Oncogene 2014 33, 3550-60. Alisertib (MLN8237) purchased from Selleck.

  • Inhibition of Aurora A (12.5 nM) by MLN8054 or MLN8237 was assessed in duplicate radiometric assays containing 100 μM [γ-32P] ATP and quantified by p81 phosphocellulose assay and scintillation counting. Kinase activity is reported as a percentage of control calculated from duplicate incubations containing 2.5% (v/v) DMSO. IC50 values represent the mean ±SEM calculated from two independent experiments.

     

     

    ACS Chem Biol 2010 5, 563-576. Alisertib (MLN8237) purchased from Selleck.

    The effects of T217D and T217N Aurora A mutations were directly compared to WT Aurora A-expressing cells. Each well was treated with either DMSO or 500 nM MLN8054 (E), or 30 nM MLN8237 (F) on day one of the experiment and cells were cultured for 8 days, at which point they were fixed. For all colony assays, an area encompassing >90 % of the colonies per dish is shown. Similar results were seen in two independent duplicate experiments.

    ACS Chem Biol 2010 5, 563-576. Alisertib (MLN8237) purchased from Selleck.

  • B, drug-treated cells were also stained with DAPI to visualize nuclear DNA and analyzed with a microscope equipped with a fluorescence digital CCD camera. Representative results are shown. Bar, 40 μm.

    J Biol Chem, 2017, 292(5):1910-1924. Alisertib (MLN8237) purchased from Selleck.

    C, Fry depletion decreases the level of Thr-210 phosphorylation of Plk1 on spindle poles. HeLa cells transfected with siRNAs were cultured in growth medium for 12 h and in thymidine-containing medium for 36 h. They were then released from thymidine arrest for 12 h before being fixed and stained with anti-Plk1 pT210 ( green) and anti-pericentrin (red) antibodies. DNA was stained with TO-PRO-3 ( blue ). For Aurora A inhibition, after release from thymidine block for 10 h, HeLa cells transfected with control siRNA were incubated for2h in medium containing MLN8237 (100 nM) and MG132 (10 μM). Magnified images of the white boxes are also shown. Scale bar ,5 μm.

    J Biol Chem 2012 287, 27670-81. Alisertib (MLN8237) purchased from Selleck.

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 NYnDVpBZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjyN48xNjVizszN NYrD[Fl4PzJiaB?= NFO5ZnpFVVOR NEG1VpFKSzVyPUCuNFQh|ryP M{K0VlI3OTN4Nki0
LS174T NVzreZQzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXiwMlUh|ryP NW[4R4hjPzJiaB?= MkHQSG1UVw>? NUjTc2hJUUN3ME2wMlA2KM7:TR?= M1njelI3OTN4Nki0
T84 M3nxXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojFNE42KM7:TR?= NH\z[JY4OiCq M2f0cWROW09? MlPOTWM2OD1yLkC5JO69VQ>? M4\WUFI3OTN4Nki0
LS180 M3nubGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3HDelAvPSEQvF2= NY\iO2M{PzJiaB?= MXjEUXNQ M1zveGlEPTB;MTFOwG0> MVGyOlE{PjZ6NB?=
SW948 NGXwVJFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUSwMlUh|ryP NUTN[|lwPzJiaB?= NXLGVpR5TE2VTx?= MWjJR|UxRTFizszN M3m2fFI3OTN4Nki0
HCT15 NIPWZnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTyNE42KM7:TR?= M3\wOlczKGh? NEjaUodFVVOR M3TneWlEPTB:MD60JO69VQ>? NH\Fc2gzPjF|Nk[4OC=>
DLD-1 NFTzZnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn33NE42KM7:TR?= NHzlbpk4OiCq MoXaSG1UVw>? NH3DbJhKSzVyPECuPEDPxE1? NILDZnEzPjF|Nk[4OC=>
MIP-101 NGeyRnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3ntZlAvPSEQvF2= NHLvbXI4OiCq MlK4SG1UVw>? NHT5fYxKSzVyPUGg{txO MmrQNlYyOzZ4OES=
SNU1544 M1Pa[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHXlVpAxNjVizszN NWrwNJg{PzJiaB?= MVPEUXNQ NXXROJBzUUN3ME2xJO69VQ>? M3LiVVI3OTN4Nki0
OCI-Ly10 MXzDfZRwfG:6aXOgRZN{[Xl? NIjibJU4OiCq M1jXeWROW09? NE\CO|NKSzVyPUCuNFU5KM7:TR?= MYiyOVg4QDN|MR?=
SU-DHL2 NHqyfWJEgXSxdH;4bYMhSXO|YYm= MoPMO|IhcA>? M4HwXGROW09? NXLKdI43UUN3ME2wMlAyKM7:TR?= MVGyOVg4QDN|MR?=
OCI-LY7 Ml\GR5l1d3SxeHnjJGF{e2G7 Mn;xO|IhcA>? NVLyTHZ6TE2VTx?= MYrJR|UxRTBwMEixJO69VQ>? NFjzNo0zPTh5OEOzNS=>
SU-DHL6 NELEVppEgXSxdH;4bYMhSXO|YYm= Mk\FO|IhcA>? NXH3TXFETE2VTx?= NFGxZo9KSzVyPUCuOFgzKM7:TR?= Mn:0NlU5Pzh|M{G=
Jeko-1 M4Xpd2N6fG:2b4jpZ{BCe3OjeR?= Ml;WO|IhcA>? MV\EUXNQ MnH0TWM2OD1yLkCyPUDPxE1? M2K3VlI2QDd6M{Ox
JVM-2 MUXDfZRwfG:6aXOgRZN{[Xl? M4\VUFczKGh? MWDEUXNQ M1XqVGlEPTB;MD6wNUDPxE1? NVf5PW9FOjV6N{izN|E>
Rec-1 NX7SdGx4S3m2b4TvfIlkKEG|c3H5 MYS3NkBp MXfEUXNQ MYLJR|UxRTBwMEi3JO69VQ>? MW[yOVg4QDN|MR?=
Z-138 MojvR5l1d3SxeHnjJGF{e2G7 M2HtU|czKGh? MlHRSG1UVw>? NHrOcmhKSzVyPUCuNFE{KM7:TR?= NX7xSmx{OjV6N{izN|E>
H9 NFzIcGtEgXSxdH;4bYMhSXO|YYm= Ml[1O|IhcA>? M2ji[2ROW09? M2q1TmlEPTB;MD62JO69VQ>? NEXzSFYzPTh5OEOzNS=>
HH MlPZR5l1d3SxeHnjJGF{e2G7 NITXU5A4OiCq MXPEUXNQ NYfPWmJPUUN3ME2wMlch|ryP NWD0WY5ROjV6N{izN|E>
DND41 NWn5e255S3m2b4TvfIlkKEG|c3H5 NWjEWGlDPzJiaB?= MnX6SG1UVw>? M4fiRWlEPTB;MD6xJO69VQ>? NFrnV2gzPTh5OEOzNS=>
CCL119 MXzDfZRwfG:6aXOgRZN{[Xl? MXi3NkBp MVXEUXNQ M1PabGlEPTB;MD6wOlIh|ryP NXj2VWhlOjV6N{izN|E>
J.Cam 1.6 MoTNR5l1d3SxeHnjJGF{e2G7 M133dVczKGh? MWfEUXNQ MnzCTWM2OD1yLkGwOUDPxE1? NGX2cYgzPTh5OEOzNS=>
Sup-T1 NHLR[3NEgXSxdH;4bYMhSXO|YYm= M4fn[|czKGh? MmnSSG1UVw>? MkXITWM2OD1{LkG0NkDPxE1? NW[0W2F6OjV6N{izN|E>
Tib 152 M4fScGN6fG:2b4jpZ{BCe3OjeR?= NXTjdHo1PzJiaB?= MornSG1UVw>? MUjJR|UxRTBwODFOwG0> NYjk[FV1OjV6N{izN|E>
MCF7 NEDYVZVHfW6ldHnvckBCe3OjeR?= MWW1JO69VQ>? MVmyOEBp NHjVO49FVVOR M4PqWWlv\HWlZYOgS|IwVSCjcoLld5Q> M2fBSlI2QDN2NECx
MDA-MB-231 M2fpdWZ2dmO2aX;uJGF{e2G7 NX;TRo9[PSEQvF2= MnzCNlQhcA>? M{\QXWROW09? M3znRmlv\HWlZYOgS|MwVSCjcoLld5Q> NXP5emEzOjV6M{S0NFE>
MCF7 MWrGeY5kfGmxbjDBd5NigQ>? M2LmVVUh|ryP M4nxS|I1KGh? NV\ne5RRTE2VTx?= M4P0fGRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsyN0OGQ{K= MWSyOVg{PDRyMR?=
MCF7 MkHaSpVv[3Srb36gRZN{[Xl? MkXjOUDPxE1? M4m5[FI1KGh? MofxSG1UVw>? MWTE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNi=> MlfTNlU5OzR2MEG=
MCF7 MkS4SpVv[3Srb36gRZN{[Xl? M1K1WFUh|ryP NGXn[2QzPCCq NUOzfW83TE2VTx?= MV\E[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiY4njcIlvKEJz Mn;kNlU5OzR2MEG=
MCF7 NHjwVVNHfW6ldHnvckBCe3OjeR?= NFrzUFY2KM7:TR?= MVqyOEBp MlPrSG1UVw>? MoC5TY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> M4LXcFI2QDN2NECx
MCF7 NIroTo1HfW6ldHnvckBCe3OjeR?= M4nQXFUh|ryP MnXkNlQhcA>? M{PaTmROW09? Mon4TY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyO{BMcXBz NYO5OoV5OjV6M{S0NFE>
MDA-MB-231 NXS0Wpo4TnWwY4Tpc44hSXO|YYm= NVn5c21HPSEQvF2= MX6yOEBp NFn5UWVFVVOR MoqwSIVkemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIFPET|EwS0SFMh?= MVeyOVg{PDRyMR?=
MDA-MB-231 NHj0O2ZHfW6ldHnvckBCe3OjeR?= NGnjSXQyKM7:TR?= NXHMWmRwOjRiaB?= MXPEUXNQ NEO0fFFKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOg>? MYKyOVg{PDRyMR?=
MDA-MB-231 MXfGeY5kfGmxbjDBd5NigQ>? M13HRVUh|ryP Mly5NlQhcA>? Mn;sSG1UVw>? NVr0V49OTGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJIN6[2yrbjDCNS=> NVPDb|NXOjV6M{S0NFE>
MDA-MB-231 NELiTGpHfW6ldHnvckBCe3OjeR?= MVK1JO69VQ>? NVnwTo51OjRiaB?= NF7pXHlFVVOR NGTLenpKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFIyKFejZkGvR4lxOQ>? M2riflI2QDN2NECx
MDA-MB-231 Mn7OSpVv[3Srb36gRZN{[Xl? MmfiOUDPxE1? MWCyOEBp MVnEUXNQ MnftTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyO{BMcXBz NUHhephkOjV6M{S0NFE>
MDA-MB-231 NXPoPFdWTnWwY4Tpc44hSXO|YYm= NIrVe|U2KM7:TR?= M2DRdlI1KGh? M3fBNGROW09? MlyzTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIIC1Ny=> NI\zWlczPTh|NESwNS=>
MCF7 M2rX[2Fxd3C2b4Ppd{BCe3OjeR?= NED1PXk2KM7:TR?= MoThNlQhcA>? MoLCSG1UVw>? NGnUe2RKdmS3Y3XzJIFxd3C2b4TpZ{Bl\WG2aB?= MV2yOVg{PDRyMR?=
MDA-MB-231 M4\pN2Fxd3C2b4Ppd{BCe3OjeR?= NXO1ZlhYPSEQvF2= MUmyOEBp NX7idm1sTE2VTx?= Mn\iTY5lfWOnczDhdI9xfG:2aXOg[IVifGh? M2rKXlI2QDN2NECx
MCF7 MY\GeY5kfGmxbjDBd5NigQ>? MnLzNUDPxE1? MWq3NkBp MoLYSG1UVw>? M4nTXWlv\HWlZYOgZZV1d3CqYXfpZ{Bl\WG2aB?= MUWyOVg{PDRyMR?=
MDA-MB-231 NFPSZ3VHfW6ldHnvckBCe3OjeR?= MYOxJO69VQ>? NYPRb2Z3PzJiaB?= M4DrTmROW09? M{\6cWlv\HWlZYOgZZV1d3CqYXfpZ{Bl\WG2aB?= M{jvcFI2QDN2NECx
U-2 OS NYrodJFzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnvwOVAh|ryP NW[zZo5HOjRiaB?= NXvDeGxPTE2VTx?= MY\JR|UxRTF4Lk[g{txO M2LG[lI2Pzl{OEGx
MG-63 NWP4[Yp5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUTsV4dtPTBizszN NXH4b4dTOjRiaB?= NW[5Z3pyTE2VTx?= NYfKcWFoUUN3ME25MlUh|ryP M1jnU|I2Pzl{OEGx
U-2 OS NGK4Zm5CeG:ydH;zbZMhSXO|YYm= MlrSOUDPxE1? NWmxPY1LOjRiaB?= NUG0VXFZTE2VTx?= NXHaS|BvUW6mdXPld{BieG:ydH;0bYMh[2WubDDk[YF1cA>? MonNNlU4QTJ6MUG=
MG-63 MlzxRZBweHSxc3nzJGF{e2G7 MXm1JO69VQ>? NXzISWNGOjRiaB?= NF3lepRFVVOR MnixTY5lfWOnczDhdI9xfG:2aXOgZ4VtdCCmZXH0bC=> NFL2eGwzPTd7MkixNS=>
U-2 OS MlWwSpVv[3Srb36gRZN{[Xl? NWnUS2RIPSEQvF2= MUOyOEBp MX7EUXNQ M4PpR3Bzd22xdHXzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? NIr5cG0zPTd7MkixNS=>
MG-63 NGnEXXdHfW6ldHnvckBCe3OjeR?= Mn\XOUDPxE1? Mo[0NlQhcA>? MYfEUXNQ MmDiVJJwdW:2ZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp NFX3UIczPTd7MkixNS=>
PANC-1 NGnTfI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M33pflUxKM7:TR?= MY[yOEBp NFrMZ3FFVVOR NWXkUYxKUUN3ME23MlEh|ryP NYPmVJNtOjV4M{KyNlU>
BxPC-3 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXPQ[lZlPTBizszN Mn[yNlQhcA>? Mnn5SG1UVw>? MorZTWM2OD14Lkig{txO MYSyOVY{OjJ{NR?=
PANC-1 NU\UeI1UTnWwY4Tpc44hSXO|YYm= MVe1JO69VQ>? M4PSN|I1KGh? MUjEUXNQ NW\xfXJSUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBqdiCJMj;NJJBp[XOn M4exelI2PjN{MkK1
BxPC-3 NWr4N3hwTnWwY4Tpc44hSXO|YYm= MYm1JO69VQ>? M{X2NlI1KGh? MXjEUXNQ NEnRXmpKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V? NUP1d5RFOjV4M{KyNlU>
PANC-1 NY\WbodOTnWwY4Tpc44hSXO|YYm= M17EVlUh|ryP NHnJfpgzPCCq MXfEUXNQ MUXJcoR2[2W|IHH1eI9xcGGpaXOgZ4VtdCCmZXH0bC=> NFzpUJQzPTZ|MkKyOS=>
BxPC-3 NYHZfoI1TnWwY4Tpc44hSXO|YYm= MX:1JO69VQ>? NFXENI0zPCCq M{\X[GROW09? NGPQO4lKdmS3Y3XzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? NHXsd|MzPTZ|MkKyOS=>
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SMS-MSN NUKzUWo4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPNRYdLOTBizszN M1;KdFk3KGh? NFHHTXpFVVOR MX\JR|UxRTBwMEKyJO69VQ>? MkjENlE1PDh3OUG=
SMS-SAN MonuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYSxPYp3OTBizszN NGntXIQ6PiCq NVz5XWo6TE2VTx?= NGrtZ3NKSzVyPUCuNFIxKM7:TR?= M3HlZ|IyPDR6NUmx
Granta-4 M2nmO2N6fG:2b4jpZ{BCe3OjeR?= NUjBXmNsOTBizszN NXXB[3JCPyCm NXHCPHBRUUN3ME2wMlA1OCEQvF2= M3;RXlIyOjlzOE[3
DB NYSwVFJ[S3m2b4TvfIlkKEG|c3H5 NIrs[HoyOCEQvF2= Mn\5O{Bl NWXrRVUyUUN3ME2wMlA1OiEQvF2= MYeyNVI6OTh4Nx?=
RL NXSwenE1S3m2b4TvfIlkKEG|c3H5 NHnTXYQyOCEQvF2= NXfxTHFtPyCm MlL1TWM2OD1yLkCxOUDPxE1? NV6wXnNsOjF{OUG4Olc>
K562 MmK0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWixNEDPxE1? MX25OkBp Mn\wTWM2OD1yLkC4O{DPxE1? MkDvNlExQTF4M{O=
LAMA-84 NUXGdo02T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXJNVAh|ryP M2q1Ulk3KGh? M4nRR2lEPTB;MD6wOVch|ryP NX[xRnNqOjFyOUG2N|M>
MM15 NW[0V4pNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVnxV5RDPCEQvF2= NEjWclM4OiCq NFXreYNFVVOR NV3YVIs3UUN3ME2wMlE{KM7:TR?= Mm\PNlA{QDJ6NES=
OPM1 MkTES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGHUUZg1KM7:TR?= M{SyNFczKGh? MUTEUXNQ MXvJR|UxRTBwMEOg{txO MmXSNlA{QDJ6NES=
RPM1 NInYSFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmHJOEDPxE1? MXS3NkBp NG\PfpRFVVOR MmDjTWM2OD1zMD6zNkDPxE1? MXGyNFM5Ojh2NB?=
INA6 NFyzVJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTUOEDPxE1? MY[3NkBp MWfEUXNQ NXXFRYQ{UUN3ME2wMlAxOiEQvF2= M1jDVVIxOzh{OES0
OPM2 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPiOEDPxE1? NEn3ZoQ4OiCq MVvEUXNQ NWrqenBNUUN3ME20MlM4KM7:TR?= Ml61NlA{QDJ6NES=
MM1R NIWxXJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzyOEDPxE1? NUfzXGdHPzJiaB?= NI\zdIRFVVOR NEfyUZpKSzVyPUGuOlgh|ryP NVzWW5pvOjB|OEK4OFQ>
DOX40 MnnVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2n2U|Qh|ryP MnrZO|IhcA>? NFi1fZJFVVOR MVLJR|UxRTVwNEig{txO NIDhelczODN6Mki0OC=>
LR5 M122bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXOwb3U4PCEQvF2= MWm3NkBp M1WyT2ROW09? NIDsXlBKSzVyPUKuOVMh|ryP M2nZVFIxOzh{OES0
U266 NHLPeXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYKyW49SPCEQvF2= MYO3NkBp NEfvcWVFVVOR MUnJR|UxRTFwNEOg{txO NYTtUpBQOjB|OEK4OFQ>
RD NWPuZmVUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYGxNEDPxE1? MX[5OkBp MYTJR|UxRTBwMkK4JO69VQ>? MVyyNFExQDN|OB?=
Rh41 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonKNVAh|ryP NYfkNWU4QTZiaB?= NHK0[2VKSzVyPUCuNFkxKM7:TR?= MVKyNFExQDN|OB?=
Rh30 MkfjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWmxNEDPxE1? MorrPVYhcA>? Ml\pTWM2OD1yLkKzNEDPxE1? NWf5V|dqOjBzMEizN|g>
BT-12 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{m3S|ExKM7:TR?= NUHr[2x1QTZiaB?= MlzWTWM2OD1yLkC2NEDPxE1? NIHMN|IzODFyOEOzPC=>
CHLA-266 NGjRelJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUfRNoduOTBizszN NFfUZZg6PiCq M3T0Z2lEPTB;MD6wO|Ih|ryP MnLQNlAyODh|M{i=
TC-71 MkLxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnXNVAh|ryP MlvVPVYhcA>? MUjJR|UxRTBwMUCyJO69VQ>? NH3DTYwzODFyOEOzPC=>
SJ-GBM2 NVPLWoRST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfVTmQyOCEQvF2= MkHEPVYhcA>? NEDCNXRKSzVyPUCuNFUxKM7:TR?= M4PNO|IxOTB6M{O4
NALM-6 MoW4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlrNNVAh|ryP NWjGPXZKQTZiaB?= M2fMdmlEPTB;MD6wOlIh|ryP Mn3SNlAyODh|M{i=
COG-LL-317 M3n2Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2fGblExKM7:TR?= M2\Jc|k3KGh? NWW2elJ7UUN3ME2wMlA1PyEQvF2= NXXoPYlvOjBzMEizN|g>
RS4-11 NUfBUHJuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHHXe2QyOCEQvF2= MUG5OkBp MnLjTWM2OD1yLkCxPEDPxE1? M4nGelIxOTB6M{O4
MOLT-4 Mn;NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\nNVAh|ryP MVu5OkBp M{H5RWlEPTB;MD6wNlYh|ryP M{HXV|IxOTB6M{O4
CCRF-CEM NVL6[4RzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUKxNEDPxE1? NVKwemh3QTZiaB?= NGPUVFJKSzVyPUCuNFk1KM7:TR?= NF:1fmYzODFyOEOzPC=>
Kasumi-1 M4nxXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVqxNEDPxE1? MkT1PVYhcA>? Mn6zTWM2OD1yLkGwN{DPxE1? NXLLO2hJOjBzMEizN|g>
Karpas-299 NUizT5RzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoG3NVAh|ryP MYK5OkBp NGnwd|NKSzVyPUCuNFM5KM7:TR?= M{LOVFIxOTB6M{O4
Ramos-RA1 MmHWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHDNVAh|ryP NWHpVZpVQTZiaB?= Ml2yTWM2OD1yLkGyO{DPxE1? MXyyNFExQDN|OB?=

... 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]
+ 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)

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 (g) = Concentration (mol/L) × Volume (L) × 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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    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 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

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

Aurora Kinase Inhibitors with Unique Features

Related Aurora Kinase Products5

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID