Alisertib (MLN8237)

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

Alisertib (MLN8237)化学構造

CAS No. 1028486-01-2

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 29500 国内在庫あり
JPY 22000 国内在庫あり
JPY 100500 国内在庫あり
JPY 265500 国内在庫あり
JPY 748500 国内在庫なし(納期7~10日)

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よく尋ねられる質問

製品安全説明書

現在のバッチを見る: 純度: 99.5%
99.5

Alisertib (MLN8237)と併用されることが多い化合物

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Metselaar DS, et al. iScience. 2022 May 13;25(6):104398.

Alisertib (MLN8237)関連製品

Aurora Kinase阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
OE33 Cytotoxic Assay 0.5 μM 24 h Decreases cell survival 22972611
FLO-1 Cytotoxic Assay 0.5 μM 24 h Decreases cell survival 22972611
AGS Cytotoxic Assay 0.5 μM 24 h Decreases cell survival 22972611
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生物活性

製品説明 Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.
特性 First orally available inhibitor of Aurora A.
Targets
Aurora A [1]
(Cell-free assay)
1.2 nM
In Vitro
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 Hexadecadrol, as well as additive effect with doxorubicin and LDP-341. [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 NSC 119875(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]

Kinase Assay 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.
細胞実験 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 Resorcinolphthalein isothiocyanate-annexin V and PI. Apoptotic cells are determined by flow cytometric analysis using BDFACS-Canto II and FlowJo software.

実験結果図 Methods Biomarkers 結果図 PMID
Western blot p-AURKA(T288) / p-EIF4E(S209) / c-Myc phospho-Aurora A / Aurora B H3S10P / H3K27me2 / H3K27me3 / H3K9me2 / H3AcK / H4K16Ac 28073841
Growth inhibition assay Cell viability 25632225
Immunofluorescence acetylated α-tubulin / γ-tubulin E-cadherin / β-catenin / vimentin / p-SMAD5 Centrin-2 / tubulin phospho-Aurora A(T288) 29401581
In Vivo
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]

動物実験 動物モデル Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells
投与量 ~30 mg/kg/day
投与経路 Orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04479306 Completed
Recurrent Lung Non-Small Cell Carcinoma|Stage IIIB Lung Cancer AJCC v8|Stage IV Lung Cancer AJCC v8|Stage IVA Lung Cancer AJCC v8|Stage IVB Lung Cancer AJCC v8
M.D. Anderson Cancer Center
June 18 2020 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
NCT02719691 Completed
Metastatic Breast Cancer|Solid Tumors
University of Colorado Denver
May 13 2016 Phase 1
NCT02367352 Terminated
Advanced Solid Tumors|Ovarian Cancer|Small Cell Lung Cancer
Millennium Pharmaceuticals Inc.|Takeda
March 19 2015 Phase 1

化学情報

分子量 518.92 化学式

C27H20ClFN4O4

CAS No. 1028486-01-2 SDF Download Alisertib (MLN8237) SDFをダウンロードする
Smiles COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC
保管

In vitro
Batch:

DMSO : 25 mg/mL ( (48.17 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機
Clear solution
5%DMSO 30% 5% 60%ddH2O
6.0mg/ml (11.56mM) Taking the 1 mL working solution as an example, add 50 μL of 120 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 600 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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Handling Instructions

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よくある質問(FAQ)

質問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.

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