Alisertib (MLN8237)

製品コードS1133 バッチS113313

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H20ClFN4O4
分子量 518.92 CAS No. 1028486-01-2
Solubility (25°C)* 体外 DMSO 100 mg/mL (192.7 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 30%PEG300 5%Tween80 60%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 6.000mg/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. 
* <1 mg/ml means slightly soluble or insoluble.
* 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.

溶剤液（一定の濃度）を調合する

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.
in vitro

Alisertib (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] Treatment with this compound (0.5 μM) inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. It 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. This compound (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, it shows strong synergistic anti-MM effect with Hexadecadrol, as well as additive effect with doxorubicin and LDP-341. [2] Treatment with MLN8237 (0.5 μM) 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]
in vivo

Alisertib (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]
特徴 First orally available inhibitor of Aurora A.

プロトコル(参考用のみ)

キナーゼアッセイ 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 this compound by using Image FlashPlates.
細胞アッセイ 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 Alisertib (MLN8237) for 24, 48, and 72 hours. Cell 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.
動物実験 動物モデル Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells
投薬量 ~30 mg/kg/day
投与方法 Orally

参考

  • https://pubmed.ncbi.nlm.nih.gov/22016509/
  • https://pubmed.ncbi.nlm.nih.gov/20382844/
  • https://pubmed.ncbi.nlm.nih.gov/22302096/

カスタマーフィードバック

Data from [Oncogene, 2014, 33, 3550-60]

Data from [Data independently produced by EMBO Mol Med, 2013, 5(1), 149-66]

Data from [Data independently produced by Cell Stem Cell, 2012, 11, 179-94]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Aurora A regulates the material property of spindle poles to orchestrate nuclear organization at mitotic exit [ EMBO J, 2025, 10.1038/s44318-025-00564-4] PubMed: 40940421
Targeted inhibition of Aurora kinase A promotes immune checkpoint inhibition efficacy in human papillomavirus-driven cancers [ J Immunother Cancer, 2025, 13(1)e009316] PubMed: 39773561
An Aurora kinase A-BOD1L1-PP2A B56 axis promotes chromosome segregation fidelity [ Cell Rep, 2025, 44(2):115317] PubMed: 39970043
The AURKA inhibitor alters the immune microenvironment and enhances targeting B7-H3 immunotherapy in glioblastoma [ JCI Insight, 2025, e173700] PubMed: 39928563
CDK1-mediated phosphorylation of LDHA fuels mitosis through LDHB-dependent lactate oxidation [ EMBO Rep, 2025, 10.1038/s44319-025-00573-8] PubMed: 40940446
Cellular senescence as a prognostic marker for predicting breast cancer progression in 2D and 3D organoid models [ Biomed Pharmacother, 2025, 189:118324] PubMed: 40616881
Actionable heterogeneity of hepatocellular carcinoma therapy-induced senescence [ Cancer Immunol Immunother, 2025, 74(7):207] PubMed: 40374812
Aurora B maintains spherical shape of mitotic cells via simultaneously stabilizing myosin II and vimentin [ J Mol Cell Biol, 2025, mjaf023] PubMed: 40795355
O 6-methylguanine DNA methyltransferase (MGMT) expression in U1242 glioblastoma cells enhances in vitro clonogenicity, tumor implantation in vivo, and sensitivity to alisertib-carboplatin combination treatment [ Front Cell Neurosci, 2025, 19:1552015] PubMed: 40336841
Overcoming MET-targeted drug resistance in MET-amplified lung cancer by aurora kinase B inhibition [ Biochim Biophys Acta Mol Cell Res, 2025, 1872(7):120001] PubMed: 40499687

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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