Alisertib (MLN8237)

製品コードS1133

Alisertib (MLN8237)化学構造

分子量(MW):518.92

Alisertib (MLN8237)は一種の選択性オーロラ(Aurora )A阻害剤で、無細胞試験でIC50値が1.2 nMです。Alisertib (MLN8237)はオーロラAに作用する選択性はオーロラ Bに作用する選択性より200倍以上が高くなります。臨床3期。

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JPY 30237.48 あり
JPY 96471.96 あり

文献中の引用(48)

カスタマーフィードバック(12)

  • 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.

  • 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.

    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.

  • 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.. 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.

  • 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.

    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.

  • 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.

    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.

製品安全説明書

Aurora Kinase阻害剤の選択性比較

生物活性

製品説明 Alisertib (MLN8237)は一種の選択性オーロラ(Aurora )A阻害剤で、無細胞試験でIC50値が1.2 nMです。Alisertib (MLN8237)はオーロラAに作用する選択性はオーロラ Bに作用する選択性より200倍以上が高くなります。臨床3期。
特性 First orally available inhibitor of Aurora A.
ターゲット
Aurora A [1]
(Cell-free assay)
Aurora B [1]
(Cell-free assay)
1.2 nM 396.5 nM
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 M2PTbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TSRVAvPSEQvF2= Mn;BO|IhcA>? Ml2wSG1UVw>? MoPlTWM2OD1yLkC0JO69VQ>? M17DblI3OTN4Nki0
LS174T Mof6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M17yWVAvPSEQvF2= NFnLSJA4OiCq NIXETZJFVVOR MYTJR|UxRTBwMEWg{txO M1yyXVI3OTN4Nki0
T84 Mln4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFPwVlcxNjVizszN M4fpTlczKGh? NXnmO5ZqTE2VTx?= NHyzc21KSzVyPUCuNFkh|ryP MWiyOlE{PjZ6NB?=
LS180 NGHrSGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MofONE42KM7:TR?= MYC3NkBp MX3EUXNQ MWrJR|UxRTFizszN M335U|I3OTN4Nki0
SW948 MnHPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnf2NE42KM7:TR?= MYW3NkBp NFj5PJNFVVOR MkDnTWM2OD1zIN88US=> M4frRlI3OTN4Nki0
HCT15 NV73c4x{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWqwMlUh|ryP MXq3NkBp MXrEUXNQ MnjmTWM2ODxyLkSg{txO NVu0O2d6OjZzM{[2PFQ>
DLD-1 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlT2NE42KM7:TR?= Mn32O|IhcA>? NHrG[5FFVVOR M1G3b2lEPTB:MD64JO69VQ>? NU\vd2o6OjZzM{[2PFQ>
MIP-101 NIXVNWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\hU4M6OC53IN88US=> MmnwO|IhcA>? MVrEUXNQ NVn6fVNNUUN3ME2xJO69VQ>? MoS2NlYyOzZ4OES=
SNU1544 NUnwV4U3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXGwMlUh|ryP NXroUJpuPzJiaB?= M4LOWWROW09? NX:5dpVjUUN3ME2xJO69VQ>? M{LpOVI3OTN4Nki0
OCI-Ly10 MnTqR5l1d3SxeHnjJGF{e2G7 NEiyXoE4OiCq M{jyVWROW09? NVXPSYlRUUN3ME2wMlA2QCEQvF2= M3TIclI2QDd6M{Ox
SU-DHL2 M3fqU2N6fG:2b4jpZ{BCe3OjeR?= NWrmR3lWPzJiaB?= M4jxcWROW09? MnfnTWM2OD1yLkCxJO69VQ>? NUfrWHoxOjV6N{izN|E>
OCI-LY7 NFXKbJNEgXSxdH;4bYMhSXO|YYm= MUG3NkBp NGDLPYRFVVOR MXzJR|UxRTBwMEixJO69VQ>? MUiyOVg4QDN|MR?=
SU-DHL6 NGDKOZREgXSxdH;4bYMhSXO|YYm= MonjO|IhcA>? MVzEUXNQ MnrzTWM2OD1yLkS4NkDPxE1? MnPhNlU5Pzh|M{G=
Jeko-1 NGfTWW1EgXSxdH;4bYMhSXO|YYm= MYG3NkBp NHTTSHNFVVOR NYPENXROUUN3ME2wMlAzQSEQvF2= NXnlW|V1OjV6N{izN|E>
JVM-2 NHTQOpdEgXSxdH;4bYMhSXO|YYm= MWO3NkBp NUfz[VZlTE2VTx?= NEDyOpJKSzVyPUCuNFEh|ryP NX\WdoZlOjV6N{izN|E>
Rec-1 NHi4d2tEgXSxdH;4bYMhSXO|YYm= MUm3NkBp NWfSVJVUTE2VTx?= MoSyTWM2OD1yLkC4O{DPxE1? NUXwenI6OjV6N{izN|E>
Z-138 NHnuWVBEgXSxdH;4bYMhSXO|YYm= MknZO|IhcA>? NYH1fWZpTE2VTx?= NEO1dnJKSzVyPUCuNFE{KM7:TR?= NFz6VoIzPTh5OEOzNS=>
H9 MnT0R5l1d3SxeHnjJGF{e2G7 NXm4W|I2PzJiaB?= M{LkOWROW09? Ml;GTWM2OD1yLk[g{txO NEfDWFczPTh5OEOzNS=>
HH MYDDfZRwfG:6aXOgRZN{[Xl? MWK3NkBp MmfOSG1UVw>? M2fSTWlEPTB;MD63JO69VQ>? M2foRVI2QDd6M{Ox
DND41 NXfJS2piS3m2b4TvfIlkKEG|c3H5 NFfNc3Q4OiCq NGTXTZRFVVOR NE\COmdKSzVyPUCuNUDPxE1? NYO4fVg1OjV6N{izN|E>
CCL119 NEPSeHREgXSxdH;4bYMhSXO|YYm= NXrMOpR6PzJiaB?= NGW3e25FVVOR NU\Xc5MzUUN3ME2wMlA3OiEQvF2= M2S5bFI2QDd6M{Ox
J.Cam 1.6 M4Dw[WN6fG:2b4jpZ{BCe3OjeR?= MkT6O|IhcA>? MY\EUXNQ MoDrTWM2OD1yLkGwOUDPxE1? NYPEb5Y3OjV6N{izN|E>
Sup-T1 M3SyRWN6fG:2b4jpZ{BCe3OjeR?= NHXjWG04OiCq M2T1N2ROW09? NHnLfVJKSzVyPUKuNVQzKM7:TR?= MX6yOVg4QDN|MR?=
Tib 152 NUPqNFZxS3m2b4TvfIlkKEG|c3H5 Mn;HO|IhcA>? NUPFempCTE2VTx?= NF33cVRKSzVyPUCuPEDPxE1? MYCyOVg4QDN|MR?=
MCF7 MleySpVv[3Srb36gRZN{[Xl? NV;4TGkxPSEQvF2= MX2yOEBp NX;zTYF{TE2VTx?= M1LFRWlv\HWlZYOgS|IwVSCjcoLld5Q> NU[2UZg5OjV6M{S0NFE>
MDA-MB-231 MYDGeY5kfGmxbjDBd5NigQ>? M3LEfVUh|ryP NVvWRXpXOjRiaB?= MoDoSG1UVw>? MnPyTY5lfWOnczDHN{9OKGG{cnXzeC=> M2PTdlI2QDN2NECx
MCF7 NUjJTVB2TnWwY4Tpc44hSXO|YYm= NWixNo5NPSEQvF2= NEnOdZEzPCCq M4j6V2ROW09? MUXE[YNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiQ1TLNU9ETEN{ MV2yOVg{PDRyMR?=
MCF7 NIOzTXRHfW6ldHnvckBCe3OjeR?= MXu1JO69VQ>? M3TCRlI1KGh? NUmxWmw{TE2VTx?= NYPmVmR5TGWlcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzJ? MkHvNlU5OzR2MEG=
MCF7 M2WxbGZ2dmO2aX;uJGF{e2G7 NF36eVU2KM7:TR?= MoHPNlQhcA>? MmHKSG1UVw>? M4\LfWRm[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDjfYNtcW5iQkG= MXiyOVg{PDRyMR?=
MCF7 MlfPSpVv[3Srb36gRZN{[Xl? MYK1JO69VQ>? NEDwSIUzPCCq M3XBRmROW09? NF\HZmVKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFIyKFejZkGvR4lxOQ>? NHn5enkzPTh|NESwNS=>
MCF7 MlTWSpVv[3Srb36gRZN{[Xl? M375WVUh|ryP M4nsWlI1KGh? M{SzdGROW09? M1jnUGlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDwNlchU2myMR?= M1HLeVI2QDN2NECx
MDA-MB-231 NW\qWHpPTnWwY4Tpc44hSXO|YYm= MoPWOUDPxE1? MXOyOEBp MUTEUXNQ NEH2SlBF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOS:FRFOy M3H5VlI2QDN2NECx
MDA-MB-231 MX\GeY5kfGmxbjDBd5NigQ>? MWqxJO69VQ>? NXLuXI1QOjRiaB?= NV6zNIVuTE2VTx?= NVXpRXNUUW6lcnXhd4V{KHSqZTDlfJBz\XO|aX;uJIxmfmWuIH;mJGNFUzJ? M2jaXlI2QDN2NECx
MDA-MB-231 MYfGeY5kfGmxbjDBd5NigQ>? M1r5WlUh|ryP MWKyOEBp NFzVU2xFVVOR NHPjVpFF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gZ5lkdGmwIFKx M{LvPVI2QDN2NECx
MDA-MB-231 NHjtXZNHfW6ldHnvckBCe3OjeR?= MljJOUDPxE1? M17jT|I1KGh? MnKzSG1UVw>? MorVTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE> MXiyOVg{PDRyMR?=
MDA-MB-231 MYnGeY5kfGmxbjDBd5NigQ>? MoDmOUDPxE1? MmHrNlQhcA>? NYr1NnJyTE2VTx?= MYnJcoNz\WG|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZicEK3JGtqeDF? MYeyOVg{PDRyMR?=
MDA-MB-231 NVHmNWY4TnWwY4Tpc44hSXO|YYm= NWDu[5FwPSEQvF2= M1PEelI1KGh? Ml[xSG1UVw>? NFnZVWNKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFU{ M{fhXFI2QDN2NECx
MCF7 M3O2W2Fxd3C2b4Ppd{BCe3OjeR?= NUDUUYpSPSEQvF2= M2C3R|I1KGh? Mk\5SG1UVw>? MX7JcoR2[2W|IHHwc5B1d3SrYzDk[YF1cA>? NGXsOm8zPTh|NESwNS=>
MDA-MB-231 MULBdI9xfG:|aYOgRZN{[Xl? NInHR5U2KM7:TR?= MknQNlQhcA>? M{H3ZmROW09? MV\JcoR2[2W|IHHwc5B1d3SrYzDk[YF1cA>? MoPXNlU5OzR2MEG=
MCF7 MlG5SpVv[3Srb36gRZN{[Xl? M3jEW|Eh|ryP NF7rR2M4OiCq M2raXGROW09? NFv6fmFKdmS3Y3XzJIF2fG:yaHHnbYMh\GWjdHi= MojFNlU5OzR2MEG=
MDA-MB-231 MUfGeY5kfGmxbjDBd5NigQ>? NVjI[VhxOSEQvF2= NV\jOJloPzJiaB?= NGjO[XVFVVOR MnjKTY5lfWOnczDheZRweGijZ3njJIRm[XSq MmnqNlU5OzR2MEG=
U-2 OS NXTwOYdoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH[xfHM2OCEQvF2= MlL1NlQhcA>? NFK0PVlFVVOR NHG4fFdKSzVyPUG2MlYh|ryP MVGyOVc6OjhzMR?=
MG-63 NYLSWFNTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIe3RnQ2OCEQvF2= NGXOc|IzPCCq NUnWRXNzTE2VTx?= MWDJR|UxRTlwNTFOwG0> NIjIO|UzPTd7MkixNS=>
U-2 OS M2XXb2Fxd3C2b4Ppd{BCe3OjeR?= Mn\jOUDPxE1? MoW5NlQhcA>? MmHXSG1UVw>? NH3xN3hKdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRp NUCy[oFLOjV5OUK4NVE>
MG-63 M1vMdGFxd3C2b4Ppd{BCe3OjeR?= NV3h[XRUPSEQvF2= NGnYOGQzPCCq MXjEUXNQ NH\KdXZKdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRp NXLH[XhVOjV5OUK4NVE>
U-2 OS NXfGN5JXTnWwY4Tpc44hSXO|YYm= NUTWcZZ7PSEQvF2= NFrLd40zPCCq MmKzSG1UVw>? M4r4XnBzd22xdHXzJIF2fG:yaHHnbYMh[2WubDDk[YF1cA>? NE\FNXYzPTd7MkixNS=>
MG-63 NUG4b2tyTnWwY4Tpc44hSXO|YYm= M2SwdlUh|ryP MUiyOEBp NWX2[3B{TE2VTx?= MXTQdo9ud3SnczDheZRweGijZ3njJINmdGxiZHXheIg> M4PSPFI2Pzl{OEGx
PANC-1 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVS1NEDPxE1? NVSze|I4OjRiaB?= MlLMSG1UVw>? NXfWcohQUUN3ME23MlEh|ryP M37jRVI2PjN{MkK1
BxPC-3 NFn0WItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPNZ5M2OCEQvF2= MlzkNlQhcA>? NHjCeYhFVVOR MXXJR|UxRTZwODFOwG0> NF\E[lMzPTZ|MkKyOS=>
PANC-1 MmjmSpVv[3Srb36gRZN{[Xl? MUe1JO69VQ>? NV7mR|VrOjRiaB?= MlTRSG1UVw>? MXHJcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2IHnuJGczN01icHjhd4U> NX:0[3k1OjV4M{KyNlU>
BxPC-3 MVPGeY5kfGmxbjDBd5NigQ>? MkSzOUDPxE1? NFW5UFUzPCCq Mor2SG1UVw>? NX;mRnFoUW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBqdiCJMj;NJJBp[XOn M3r1ZVI2PjN{MkK1
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SMS-KANR NFvIb2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1zZVFExKM7:TR?= MXq5OkBp NF3Sd3NFVVOR MXXJR|UxRTBwMEK2JO69VQ>? NH3OfZQzOTR2OEW5NS=>
SMS-KCN NH3wbotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYPRbYk4OTBizszN NV3ZWJpsQTZiaB?= NUnvNZNRTE2VTx?= MUXJR|UxRTBwMEG5JO69VQ>? NFr1Zm8zOTR2OEW5NS=>
SMS-KCNR MmjTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHK5VZIyOCEQvF2= MnHXPVYhcA>? NUDhXJJPTE2VTx?= MYTJR|UxRTBwMEGwJO69VQ>? M1PJPFIyPDR6NUmx
SMS-LHN MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHrQbFgyOCEQvF2= M1y4dVk3KGh? MXXEUXNQ NFTyUIxKSzVyPUCuNFMzKM7:TR?= M2rpOFIyPDR6NUmx
SMS-MSN MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYmxNEDPxE1? M3;oXFk3KGh? NWKyZXUyTE2VTx?= M{foOWlEPTB;MD6wNlIh|ryP M17KTlIyPDR6NUmx
SMS-SAN NFnkXWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWWxNEDPxE1? MkXhPVYhcA>? MVLEUXNQ MorMTWM2OD1yLkCyNEDPxE1? NEjZOpUzOTR2OEW5NS=>
Granta-4 MmXCR5l1d3SxeHnjJGF{e2G7 Mnv4NVAh|ryP NUHOPGI{PyCm M{i3cWlEPTB;MD6wOFAh|ryP M3;nZ|IyOjlzOE[3
DB M{nOSmN6fG:2b4jpZ{BCe3OjeR?= MoD2NVAh|ryP M4H2NVch\A>? NGDWTpJKSzVyPUCuNFQzKM7:TR?= NVLtUZd3OjF{OUG4Olc>
RL MX\DfZRwfG:6aXOgRZN{[Xl? NGnSVZYyOCEQvF2= MnO2O{Bl MUXJR|UxRTBwMEG1JO69VQ>? NFfNU5EzOTJ7MUi2Oy=>
K562 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYGxNEDPxE1? NUnvOmMyQTZiaB?= NVvkcHBmUUN3ME2wMlA5PyEQvF2= M37MNVIyODlzNkOz
LAMA-84 NYq2[5NJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXOxNEDPxE1? MorhPVYhcA>? M{HkN2lEPTB;MD6wOVch|ryP NWKxOFN3OjFyOUG2N|M>
MM15 M{DrcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoPyOEDPxE1? MVS3NkBp MWLEUXNQ NGDhU4tKSzVyPUCuNVMh|ryP MknpNlA{QDJ6NES=
OPM1 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nVRVQh|ryP M3nhbVczKGh? NX;JWI9ITE2VTx?= NY\WbHBsUUN3ME2wMlA{KM7:TR?= M4\BNFIxOzh{OES0
RPM1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4T2XFQh|ryP MkLCO|IhcA>? MX;EUXNQ NFS1[lNKSzVyPUGwMlMzKM7:TR?= MlX2NlA{QDJ6NES=
INA6 MkL1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{POUlQh|ryP NVzW[21uPzJiaB?= Ml74SG1UVw>? MnjoTWM2OD1yLkCwNkDPxE1? MUOyNFM5Ojh2NB?=
OPM2 NFLDcGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3O2[lQh|ryP Mk\FO|IhcA>? MWDEUXNQ M1vSWGlEPTB;ND6zO{DPxE1? MoO5NlA{QDJ6NES=
MM1R Ml7MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjwWGdtPCEQvF2= MW[3NkBp NIrKXnBFVVOR NV:xfIF7UUN3ME2xMlY5KM7:TR?= NVqyWGNuOjB|OEK4OFQ>
DOX40 NITrfG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVy0JO69VQ>? M2f6cVczKGh? MWnEUXNQ M{[zV2lEPTB;NT60PEDPxE1? NHntdWkzODN6Mki0OC=>
LR5 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmi5OEDPxE1? M{DkTFczKGh? NIWw[FlFVVOR MWrJR|UxRTJwNUOg{txO NEfET5QzODN6Mki0OC=>
U266 NUHhdpV7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWnRdVZrPCEQvF2= MmjCO|IhcA>? NUn1elFUTE2VTx?= M4K4d2lEPTB;MT60N{DPxE1? NVHzcXZ4OjB|OEK4OFQ>
RD NVnQXYZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MU[xNEDPxE1? MVq5OkBp NWnae5ByUUN3ME2wMlIzQCEQvF2= MkDDNlAyODh|M{i=
Rh41 NIT0T4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1znblExKM7:TR?= MkPFPVYhcA>? NVTDcnNuUUN3ME2wMlA6OCEQvF2= M{CyVVIxOTB6M{O4
Rh30 NV;QVHBjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnibphIOTBizszN NHfUR4I6PiCq MnTDTWM2OD1yLkKzNEDPxE1? NEjQfZUzODFyOEOzPC=>
BT-12 MkTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWH4VWxiOTBizszN MUK5OkBp MXHJR|UxRTBwME[wJO69VQ>? NWD6PFZROjBzMEizN|g>
CHLA-266 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUSxNEDPxE1? MVK5OkBp NH6xOItKSzVyPUCuNFczKM7:TR?= NGTTRoozODFyOEOzPC=>
TC-71 M3\JSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXWxNEDPxE1? MkfEPVYhcA>? NYrzbIRMUUN3ME2wMlExOiEQvF2= Mln1NlAyODh|M{i=
SJ-GBM2 NXzSUlBvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2DEUlExKM7:TR?= NF71VFk6PiCq NWHyV|ZxUUN3ME2wMlA2OCEQvF2= MmPSNlAyODh|M{i=
NALM-6 NWXFdpBrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmTmNVAh|ryP M1Xye|k3KGh? NIDxSmdKSzVyPUCuNFYzKM7:TR?= MWeyNFExQDN|OB?=
COG-LL-317 MlP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MojYNVAh|ryP NWLMVlE4QTZiaB?= NX\0V29ZUUN3ME2wMlA1PyEQvF2= NVHzc|RTOjBzMEizN|g>
RS4-11 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1S4TlExKM7:TR?= MYG5OkBp NIfZUmxKSzVyPUCuNFE5KM7:TR?= MVeyNFExQDN|OB?=
MOLT-4 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{eyPFExKM7:TR?= NI\BemM6PiCq MmXiTWM2OD1yLkCyOkDPxE1? M1\teVIxOTB6M{O4
CCRF-CEM NEjWeFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX3TNpVmOTBizszN NV;od2luQTZiaB?= MY\JR|UxRTBwMEm0JO69VQ>? NUThO4tWOjBzMEizN|g>
Kasumi-1 M1H5WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1TzdlExKM7:TR?= M4TMSVk3KGh? MVXJR|UxRTBwMUCzJO69VQ>? MXuyNFExQDN|OB?=
Karpas-299 NXTyTHhqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1;qW|ExKM7:TR?= NHvrUIU6PiCq NFe0fJBKSzVyPUCuNFM5KM7:TR?= MXqyNFExQDN|OB?=
Ramos-RA1 MkLRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX3mN5o4OTBizszN NH;4SXM6PiCq MlL2TWM2OD1yLkGyO{DPxE1? M2DSfFIxOTB6M{O4

多くの細胞株試験データを見る場合、クリックしてください

体内試験 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]

お薦めの試験操作(参考用のみ)

キナーゼ試験:[1]
+ 展開

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.
細胞試験: [2]
+ 展開
  • 細胞株: MM1.S, MM.1R, LR5, RPMI 8226, DOX40, OPM1, OPM2, INA6, and U266
  • 濃度: Dissolved in DMSO, final concentrations ~10 μM
  • 反応時間: 24, 48, and 72 hours
  • 実験の流れ: 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.
    (参考用のみ)
動物試験:[2]
+ 展開
  • 動物モデル: Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells
  • 製剤: Formulated in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate
  • 投薬量: ~30 mg/kg/day
  • 投与方法: Orally
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 27 mg/mL (52.03 mM)
Water Insoluble
Ethanol Insoluble
体内 順序で溶剤を入れること:
15% Captisol
30 mg/mL

* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 518.92
化学式

C27H20ClFN4O4

CAS No. 1028486-01-2
保管
in solvent
別名 N/A

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • 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):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02860000 Not yet recruiting Estrogen Receptor Negative|Estrogen Receptor Positive|HER2/Neu Negative|Postmenopausal|Stage IIIA Breast Cancer|Stage IIIB Breast Cancer|Stage IIIC Breast Cancer|Stage IV Breast Cancer Mayo Clinic|National Cancer Institute (NCI) December 2016 Phase 2
NCT02812056 Not yet recruiting 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
NCT02700022 Recruiting Diffuse Large B-cell Lymphoma|Follicular Lymphoma|Burkitt Lymphoma UNC Lineberger Comprehensive Cancer Center|Millennium Pharmaceuticals, Inc. July 2016 Phase 1
NCT02719691 Recruiting Metastatic Breast Cancer|Solid Tumors University of Colorado, Denver May 2016 Phase 1
NCT02560025 Recruiting Acute Myeloid Leukemia Massachusetts General Hospital|Takeda December 2015 Phase 2
NCT02551055 Active, not recruiting Neoplasms, Advanced or Metastatic Millennium Pharmaceuticals, Inc.|Takeda October 2015 Phase 1

技術サポート

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

よくある質問(FAQ)

  • 問題1:

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

  • 回答:

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

Aurora Kinase信号経路図

Aurora Kinase Inhibitors with Unique Features

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID