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MLN8054

Cat. No. M1751
MLN8054 Structure
Size Price Availability Quantity
2mg USD 75  USD75 In stock
5mg USD 108  USD108 In stock
10mg USD 198  USD198 In stock
50mg USD 600  USD600 In stock
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Quality Control & Documentation
Biological Activity

MLN8054 is an orally bioavailable, highly selective small molecule inhibitor of Aurora with IC50s of 0.004uM and 0.172uM. for Aurora A and Aurora B.Auora kinase inhibitor MLN8054 binds to and inhibits Aurora kinase A, resulting in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregration, and inhibition of cell proliferation.

Customer Product Validations & Biological Datas
Source Int J Radiat Oncol Biol Phys (2011). Figure 1. MLN8054
Method Western blots
Cell Lines DU145 cells
Concentrations 1 μM
Incubation Time 1 h
Results When MLN8054 was administered in combination with radiation, total Aurora-A remained elevated, but phospho-Aurora-A levels were reduced nearly to baseline levels, indicating abrogation of Aurora-A activity
Protocol (for reference only)
Cell Experiment
Cell lines HCT116, PC-3, SW480, DLD-1, MCF-7, MDA-MB-231, Calu-6, H460 and SKOV-3 cell lines
Preparation method Cell Viability Analysis. Human tumor cell lines obtained from the American Type Culture Collection were grown in 96-well cell culture dishes according to the distributor's recommendations. MLN8054, diluted in DMSO, was added to the cells in 2-fold serial dilutions to achieve final concentrations ranging from 10 to 0.04 mM. MLN8054 at each dilution was added in triplicate with each replicate on a separate plate. Cells treated with DMSO (n = 6 wells per plate; 0.2% final concentration) served as the untreated control. The cells were treated with MLN8054 for 96 h at 37°C in a humidified cell culture chamber. Cell viability in each cell line was measured by using the Cell Proliferation ELISA, BrdU colorimetric kit according to the manufacturer's recommendations (Roche).
Concentrations 0.04~10 mM
Incubation time 96 hr
Animal Experiment
Animal models Female (HCT-116) and male (PC3) athymic nude NCR (nu/nu) mice
Formulation 10% hydroxypropyl-β-cyclodextrin (Sigma) with 5% sodium bicarbonate
Dosages 10 or 30 mg/kg BID or 30mg/kg QD for 21 consecutive days
Administration orally
Chemical Information
Molecular Weight 476.86
Formula C25H15ClF2N4O2
CAS Number 869363-13-3
Solubility (25°C) DMSO 75 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Yang Y et al. Mol Biosyst. Molecular dynamics and free energy studies on Aurora kinase A and its mutant bound with MLN8054: insight into molecular mechanism of subtype selectivity.

[2] Wunderlich A et al. Endocrine. Combined inhibition of cellular pathways as a future therapeutic option in fatal anaplastic thyroid cancer.

[3] Moretti L et al. Int J Radiat Oncol Biol Phys. MLN8054, a small molecule inhibitor of aurora kinase a, sensitizes androgen-resistant prostate cancer to radiation.

[4] Chakravarty A et al. Cancer Res. Phase I assessment of new mechanism-based pharmacodynamic biomarkers for MLN8054, a small-molecule inhibitor of Aurora A kinase.

[5] Macarulla T et al. Mol Cancer Ther. Phase I study of the selective Aurora A kinase inhibitor MLN8054 in patients with advanced solid tumors: safety, pharmacokinetics, and pharmacodynamics.

[6] Sloane DA et al. ACS Chem Biol. Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237.

[7] Huck JJ et al. Mol Cancer Res. MLN8054, an inhibitor of Aurora A kinase, induces senescence in human tumor cells both in vitro and in vivo.

[8] Manfredi MG, et al. Proc Natl Acad Sci U S A. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase.

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Keywords: MLN8054 supplier, Aurora Kinase, inhibitors, activators


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