MLN8054

Catalog No.S1100

MLN8054 Chemical Structure

Molecular Weight(MW): 476.86

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.

Size Price Stock Quantity  
In DMSO USD 238 In stock
USD 170 In stock
USD 320 In stock
USD 970 In stock

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3 Customer Reviews

  • Aurora A and Aurora B activities do not influence the timing of CENP-A assembly. (A) A nascent pool of CENP-A-SNAP was pulse labeled in randomly cycling HeLa cells during which either Aurora A or Aurora B activity was inhibited by treatment with 1µM of MLN8054 or 2µM of ZM447439, respectively. Cells were fixed and counterstained for cyclin B1, CENP-T and with DAPI to indicate G2 status, centromeres and DNA, respectively. Effective kinase inhibition was evident from chromosome segregation defects in mitosis after Aurora A inhibition [indicated by an asterisk and (Hoar et al., 2007)] prior to subsequent CENP-A assembly in G1 or after Aurora B inhibition resulting in cytokinesis failure and multinucleated cells [asterisk and (Ditchfield et al., 2003)]. Representative images of cells in G1 (low cyclin B) and G2 phase (high cyclin B) are shown. (B) Experiment as in A except  that  cells  were  treated  for  one  hour  with  either  Roscovitine  alone  or  in  combination  with  MLN8054  or ZM447439 prior to fixation. Percentage of cells assembling CENP-A-SNAP is indicated [either percent of total cells (in top panel, G1 phase) or percent of cyclin B1 positive cells (bottom panel, G2 phase)]. 

    Dev Cell 2012 22, 52-63. MLN8054 purchased from Selleck.

    Stacked column graphic representing  the effect of the small molecule MLN8054 throughout oocyte developmental progress, namely during metaphase I, telophase I and metaphase II oocytes in different conditions.

    2013 Professora Dra.maria Gabriela Rodrigues(DBA/FCUL). MLN8054 purchased from Selleck.

  • Western blot analysis of p-Aurora A and Aurora A. 0-10μM MLN8054 was added.

     

     

    2011 Dr. Zhang of Tianjin Medical University. MLN8054 purchased from Selleck.

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description 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.
Targets
Aurora A [1]
(Sf9 cells)
Aurora B [1]
(Sf9 cells)
LCK [1]
(Sf9 cells)
PKA [1]
(Sf9 cells)
CK2 [1]
(Sf9 cells)
4 nM 172 nM 3.2 μM 19 μM 20.5 μM
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]

Protocol

Kinase Assay
+ Expand

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.
Cell Research
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  • Cell lines: HCT-116, SW480, DLD-1, MCF-7, MDA-MB-231, Calu-6, H460, SKOV-3 and PC-3 cells
  • Concentrations: 0.04-10 mM
  • Incubation Time: 96 hours
  • Method: 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
    (Only for Reference)
Animal Research
+ Expand
  • Animal Models: HCT-116 and PC-3 cells are injected s.c. into the right flank of nude mice.
  • Formulation: MLN8054 is dissolved in 10% hydroxypropyl-β-cyclodextrin with 5% sodium bicarbonate.
  • Dosages: ≤30 mg/kg
  • Administration: Administered via p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 95 mg/mL (199.21 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 15% Captisol 30 mg/mL

* 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.

Chemical Information

Molecular Weight 476.86
Formula

C25H15ClF2N4O2

CAS No. 869363-13-3
Storage powder
in solvent
Synonyms N/A

Bio Calculators

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Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00652158 Terminated Advanced Malignancies Millennium Pharmaceuticals, Inc. April 2006 Phase 1
NCT00249301 Terminated Breast Neoplasm|Colon Neoplasm|Pancreatic Neoplasm|Bladder Neoplasm Millennium Pharmaceuticals, Inc. October 2005 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Aurora Kinase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID