MLN8054

製品コードS1100 バッチS110002

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

C25H15ClF2N4O2
分子量 476.86 CAS No. 869363-13-3
Solubility (25°C)* 体外 DMSO 95 mg/mL (199.21 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
15% Captisol
10.0mg/ml Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 15% Captisol clear solution, and mix evenly to form a uniform suspension. 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 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.
in vitro MLN8054 is an ATP-competitive, reversible inhibitor of recombinant Aurora A kinase with an IC50 of 4 nM, which shows >40-fold more selective inhibitory activity for Aurora A compared with Aurora B. [1] In vitro, MLN8054 exhibits the activity of growth inhibition across various cell lines from diverse tissue origins with IC50 values ranging from 0.11 μM to 1.43 μM. In addition, MLN8054 selectively inhibits Aurora A over Aurora B in cultured cells, and inhibits cell proliferation by promoting G2/M accumulation and spindle defects in multiple cultured human tumor cells lines. [1] A recent study shows that MLN8054 sensitizes androgen-resistant prostate cancer to radiation by inhibiting Aurora A kinase, which is associated with sustained DNA double-strand breaks. [2]
in vivo In the HCT-116 tumor-bearing mice, MLN8054, administered orally at 3 mg/kg, 10 mg/kg, and 30 mg/kg once a day, leads to dose-dependent tumor growth inhibition (TGI: 76% and 84% for 10 mg/kg and 30 mg/kg). MLN8054 also shows similar antitumor activity in the PC-3 tumor xenograft in nude mice. [1] In the HCT-116 xenograft-bearing animals, MLN8054 induces DNA and tubulin staining of tumor tissue in nuclear and cell body area, consistent with a senescent phenotype by increasing senescence-associated beta-galactosidase activity. [3]

プロトコル(参考用のみ)

キナーゼアッセイ Enzyme Assays
Recombinant murine Aurora A and Aurora B protein are 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 by using Image FlashPlates. Aurora B kinase (2 nM) is assayed with 10 μM biotinylated peptide Biotin-TKQTARKSTGGKAPR in 50 mM Tricine (pH 8.0)/2.5 mM MgCl2/5 mM DTT/10% glycerol/2% BSA/40 μCi/ml [γ-33P]ATP at 250 μM. The conditions for all other in vitro kinase assays are available upon request. MLN8054 is run in a 226 kinase screen at a 1 μM compound concentration with an ATP concentration of 10 μM for all assays.
細胞アッセイ 細胞株 HCT-116, SW480, DLD-1, MCF-7, MDA-MB-231, Calu-6, H460, SKOV-3 and PC-3 cells
濃度 0.04-10 mM
反応時間 96 hours
実験の流れ Human tumor cell lines are grown in 96-well cell culture dishes according to the distributor's recommendations. MLN8054, diluted in DMSO, is added to the cells in 2-fold serial dilutions to achieve final concentrations ranging from 10 mM to 0.04 mM. MLN8054 at each dilution is added in triplicate with each replicate on a separate plate. Cells treated with DMSO (n = 6 wells per plate; 0.2% final concentration) serves as the untreated control. The cells are treated with MLN8054 for 96 hours at 37 °C in a humidified cell culture chamber. Cell viability in each cell line is measured by using the Cell Proliferation ELISA, BrdU colorimetric kit according to the manufacturer's recommendation
動物実験 動物モデル HCT-116 and PC-3 cells are injected s.c. into the right flank of nude mice.
投薬量 ≤30 mg/kg
投与方法 Administered via p.o.

カスタマーフィードバック

, 2013, Professora Dra.maria Gabriela Rodrigues(DBA/FCUL)

Data from [Dev Cell, 2012, 22, 52-63]

, 2011, Dr. Zhang of Tianjin Medical University

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：

Detection of senescence using machine learning algorithms based on nuclear features [ Nat Commun, 2024, 15(1):1041] PubMed: 38310113
CENP-E activation by Aurora A and B controls kinetochore fibrous corona disassembly [ Nat Commun, 2023, 14(1):5317] PubMed: 37658044
Mitotic DNA damage promotes chromokinesin-mediated missegregation of polar chromosomes in cancer cells [ Mol Biol Cell, 2023, 34(5):ar47] PubMed: 36989031
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
PD-LI promotes rear retraction during persistent cell migration by altering integrin β4 dynamics [ Cell Rep, 2022, 39(2):110690] PubMed: 35417684
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575] PubMed: 35326726
Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis [ Cancer Cell, 2021, S1535-6108(21)00383-4] PubMed: 34388376
Inhibition of CDK4/6 promotes CD8 T-cell memory formation [ Cancer Discov, 2021, candisc.1540.2020] PubMed: 33941591
PARP1 and CHK1 coordinate PLK1 enzymatic activity during the DNA damage response to promote homologous recombination-mediated repair [ Nucleic Acids Res, 2021, gkab584] PubMed: 34197606
Size-Selective VAILase Proteolysis Provides Dynamic Insights into Protein Structures [ Anal Chem, 2021, 93(30):10653-10660] PubMed: 34291915

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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