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Cell Cycle/Checkpoint Aurora Kinase Alisertib

Alisertib

Catalog No. T2241   CAS 1028486-01-2
Synonyms: MLN 8237

Alisertib (MLN8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib is >200-fold higher for Aurora A than Aurora B.

Alisertib, CAS 1028486-01-2
Pack Size Availability Price/USD Quantity
2 mg In stock 32.00
5 mg In stock 56.00
10 mg In stock 98.00
25 mg In stock 175.00
50 mg In stock 312.00
100 mg In stock 450.00
200 mg In stock 820.00
1 mL * 10 mM (in DMSO) In stock 64.00
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Description Alisertib (MLN8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib is >200-fold higher for Aurora A than Aurora B.
Targets&IC50 Aurora A :ic50 1.2nM,   Aurora B :ic50 396.5nM,  
In vitro Treatment of cultured MM cells with Alisertib (MLN8237) results in mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence. In addition, MLN8237 up-regulates p53 and tumor suppressor genes p21 and p27. Combining MLN8237 with dexamethasone, doxorubicin, or bortezomib induces synergistic/additive anti-MM activity in vitro [1]. Alisertib inhibited AAK over ABK with a selectivity of more than 200-fold in cells. Alisertib inhibited proliferation of human tumor cell lines in vitro [2]. A T217D/W277E double mutant exhibits superior levels of resistance to MLN8237, with the I50 value increasing approximately 20-fold from 30 to 650 nM in the presence of TPX2 [3].
In vivo Tumor burden was significantly reduced and overall survival was significantly increased in animals treated with 30 mg/kg MLN8237 for 21 days. Induction of apoptosis and cell death by MLN8237 were confirmed in tumor cells excised from treated animals by TdT-mediated dUTP nick end labeling assay [1]. Alisertib produced a dose-dependent decrease in bipolar and aligned chromosomes in the HCT-116 xenograft model. Alisertib produced tumor growth inhibition in solid tumor xenograft models and regressions in in vivo lymphoma models. In addition, a dose of alisertib that caused tumor stasis, as measured by volume, resulted in a decrease in FLT uptake [2]. Nude mice bearing human tumor xenografts treated with a single oral dose of alisertib (20 mg/kg) displayed a phenotype consistent with inhibition of Aurora A [4].
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.
Cell Research
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.(Only for Reference)
Cell lines: MM1.S, MM.1R, LR5, RPMI 8226, DOX40, OPM1, OPM2, INA6, and U266
Animal Research
Animal Model: Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells
Synonyms MLN 8237
Purity 99.82%
Molecular Weight 518.92
Formula C27H20ClFN4O4
CAS No. 1028486-01-2

Storage

-20℃ 3 years powder

-80℃ 2 years in solvent

Solubility Information

DMSO: 26 mg/mL (50.1 mM)

Ethanol: <1 mg/mL

Water: <1 mg/mL

( < 1 mg/ml refers to the product slightly soluble or insoluble )

Solution 1

15% Captisol: 30 mg/mL

Citations

References and Literature
1. Güllü G, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma Blood June 24, 2010 vol. 115 no. 25 5202-5213 2. Manfredi MG, et al. Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays. Clin Cancer Res. 2011 Dec 15;17(24):7614-24. 3. Sloane DA, et al. Drug-Resistant Aurora A Mutants for Cellular Target Validation of the Small Molecule Kinase Inhibitors MLN8054 and MLN8237. ACS Chem Biol. 2010 Jun 18;5(6):563-76. 4. Sells TB, et al. MLN8054 and Alisertib (MLN8237): Discovery of Selective Oral Aurora A Inhibitors. ACS Med Chem Lett. 2015 Apr 22;6(6):630-4.

Related compound libraries

This product is contained In the following compound libraries:
Bioactive Compound Library Inhibitor Library Anti-cancer Compound Library Clinical Compound Library Autophagy Compound Library Epigenetics Compound Library DNA Damage & Repair Compound Library Kinase Inhibitor Library Anti-cancer Clinical Compound Library Fluorochemical Library Cell cycle related Compound Library

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