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MLN8054 Aurora Kinase inhibitor

Cat.No.S1100

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.
MLN8054 Aurora Kinase inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 476.86

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Quality Control

Batch: Purity: 99.91%
99.91

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 cells Function assay Inhibition of mouse recombinant Aurora A kinase expressed in insect Sf9 cells by radioactive flashplate assay, IC50=4 nM
human HCT116 cells Function assay Inhibition of aurora kinase A autophosphorylation at T288 in human HCT116 cells by immunofluorescence analysis, IC50=0.034 μM
human HeLa cells Function assay 1 h Inhibition of Aurora A Thr288 autophosphorylation in human HeLa cells after 1 hr, IC50=0.034 μM
human H460 cells Proliferation assay 96 h Antiproliferative activity against human H460 cells after 96 hrs by BrdU cell proliferation ELISA, IC50=0.11 μM
human HT-29 cells Proliferation assay 4 days Antiproliferative activity against human HT-29 cells after 4 days by celltiter assay, IC50=0.15 μM
human Calu6 cells Proliferation assay 96 h Antiproliferative activity against human Calu6 cells after 96 hrs by BrdU cell proliferation ELISA, IC50=0.22 μM
human SKOV3 cells Proliferation assay 96 h Antiproliferative activity against human SKOV3 cells after 96 hrs by BrdU cell proliferation ELISA, IC50=0.53 μM
human MCF7 cells Proliferation assay 96 h Antiproliferative activity against human MCF7 cells after 96 hrs by BrdU cell proliferation ELISA, IC50=0.67 μM
human MDAMB231 cells Proliferation assay 96 h Antiproliferative activity against human MDAMB231 cells after 96 hrs by BrdU cell proliferation ELISA, IC50=0.74 μM
human PC3 cells Proliferation assay 96 h Antiproliferative activity against human PC3 cells after 96 hrs by BrdU cell proliferation ELISA, IC50=0.79 μM
human SW480 cells Proliferation assay 96 h Antiproliferative activity against human SW480 cells after 96 hrs by BrdU cell proliferation ELISA, IC50=0.86 μM
human DLD1 cells Proliferation assay 96 h Antiproliferative activity against human DLD1 cells after 96 hrs by BrdU cell proliferation ELISA, IC50=1.43 μM
DU-145 prostate cancer cell Function assay 96 h Inhibitory concentration against DU-145 prostate cancer cell proliferation over 96 hr, IC50=0.11 μM
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Solubility

In vitro
Batch:

DMSO : 95 mg/mL (199.21 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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Dilution Calculator Molecular Weight Calculator

In vivo
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In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight 476.86 Formula

C25H15ClF2N4O2

 Storage (From the date of receipt)
CAS No. 869363-13-3 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1C2=CN=C(N=C2C3=C(C=C(C=C3)Cl)C(=N1)C4=C(C=CC=C4F)F)NC5=CC=C(C=C5)C(=O)O

Mechanism of Action

Targets/IC50/Ki
Aurora A
(Sf9 cells)
4 nM
Aurora B
(Sf9 cells)
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. In vitro, this compound 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, it 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. A recent study shows that this chemical sensitizes androgen-resistant prostate cancer to radiation by inhibiting Aurora A kinase, which is associated with sustained DNA double-strand breaks.
Kinase Assay
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. This compound is run in a 226 kinase screen at a 1 μM compound concentration with an ATP concentration of 10 μM for all assays.
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). This compound also shows similar antitumor activity in the PC-3 tumor xenograft in nude mice. In the HCT-116 xenograft-bearing animals, it 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.
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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