Alisertib (MLN8237)

Catalog No.S1133 Batch:S113313

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Technical Data

Formula

C27H20ClFN4O4

Molecular Weight 518.92 CAS No. 1028486-01-2
Solubility (25°C)* In vitro DMSO 100 mg/mL (192.7 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 30%PEG300 5%Tween80 60%ddH2O
6.0mg/ml 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.
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 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]

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]

Features First orally available inhibitor of Aurora A.

Protocol (from reference)

Kinase Assay:

[1]

  • 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 Assay:

[2]

  • 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 Resorcinolphthalein isothiocyanate-annexin V and PI. Apoptotic cells are determined by flow cytometric analysis using BDFACS-Canto II and FlowJo software.

Animal Study:

[2]

  • Animal Models

    Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells

  • Dosages

    ~30 mg/kg/day

  • Administration

    Orally

Customer Product Validation

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]

Data from [EMBO J, 2012, 30, 906-19]

Selleck's Alisertib (MLN8237) has been cited by 392 publications

Detection of senescence using machine learning algorithms based on nuclear features [ Nat Commun, 2024, 15(1):1041] PubMed: 38310113
Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse [ Cell Rep Med, 2024, 5(3):101471] PubMed: 38508142
Meningioma achieves malignancy and erastin-induced ferroptosis resistance through FOXM1-AURKA-NRF2 axis [ Redox Biol, 2024, 72:103137] PubMed: 38642502
The Eμ-Ret mouse is a novel model of hyperdiploid B-cell acute lymphoblastic leukemia [ Leukemia, 2024, 38(5):969-980] PubMed: 38519798
AurkA/TPX2 co-overexpression in nontransformed cells promotes genome instability through induction of chromosome mis-segregation and attenuation of the p53 signalling pathway [ Biochim Biophys Acta Mol Basis Dis, 2024, 1870(4):167116] PubMed: 38447882
Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions [ Sci Rep, 2024, 14(1):4303] PubMed: 38383756
Visualization strategies to aid interpretation of high-dimensional genotoxicity data [ Environ Mol Mutagen, 2024, 10.1002/em.22604] PubMed: 38757760
Multiple intersecting pathways are involved in the phosphorylation of CPEB1 to activate translation during mouse oocyte meiosis [ bioRxiv, 2024, 2024.01.17.575938] PubMed: 38293116
NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation [ bioRxiv, 2024, 2024.02.22.581432] PubMed: 38464226
Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry [ Nat Commun, 2023, 14(1):355] PubMed: 36683055

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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