MLN8054

Catalog No.S1100 Batch:S110001

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Technical Data

Formula

C25H15ClF2N4O2
Molecular Weight 476.86 CAS No. 869363-13-3
Solubility (25°C)* In vitro DMSO 95 mg/mL (199.21 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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)
4 nM 172 nM
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 (from reference)

Kinase Assay:[1]
  • 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 Assay:[1]
  • 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
Animal Study:[1]
  • Animal Models

    HCT-116 and PC-3 cells are injected s.c. into the right flank of nude mice.

  • Dosages

    ≤30 mg/kg

  • Administration

    Administered via p.o.

References

  • https://pubmed.ncbi.nlm.nih.gov/17360485/
  • https://pubmed.ncbi.nlm.nih.gov/21514073/
  • https://pubmed.ncbi.nlm.nih.gov/20197380/

Customer Product Validation

<p>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.</p>

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

<p>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)]. </p>

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

<p>Western blot analysis of p-Aurora A and Aurora A. 0-10μM MLN8054 was added.</p><div><div> </div></div><p> </p>

, 2011 , Dr. Zhang of Tianjin Medical University

Selleck's MLN8054 Has Been Cited by 51 Publications

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

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.