Name: MLN8054
Brand: Selleck Chemicals
SKU: S1100
Rating: 5 (50 reviews)

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 Chemical Structure

CAS: 869363-13-3

Selleck's MLN8054 has been cited by 50 publications

Purity & Quality Control

Batch: Purity: 99.91%

99.91

MLN8054 Related Products

Related Targets	Aurora A Aurora B Aurora C Aurora B	Click to Expand
Related Compound Libraries	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	Click to Expand

Signaling Pathway

Aurora Kinase Signaling Pathway

Choose Selective Aurora Kinase Inhibitors

Cell Data

Cell Lines	Assay Type	Incubation Time	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	17360485
human HCT116 cells	Function assay		Inhibition of aurora kinase A autophosphorylation at T288 in human HCT116 cells by immunofluorescence analysis, IC50=0.034 μM	26101564
human HeLa cells	Function assay	1 h	Inhibition of Aurora A Thr288 autophosphorylation in human HeLa cells after 1 hr, IC50=0.034 μM	17360485
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	17360485
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	19402633
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	17360485
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	17360485
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	17360485
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	17360485
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	17360485
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	17360485
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	17360485
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	16107152
Click to View More Cell Line Experimental Data

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
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]
Kinase Assay	Enzyme Assays
Kinase Assay	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	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

In Vivo
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]
Animal Research	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.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
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

References

Chemical Information & Solubility

Molecular Weight	476.86	Formula	C₂₅H₁₅ClF₂N₄O₂
CAS No.	869363-13-3	SDF	Download MLN8054 SDF
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
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 95 mg/mL ( (199.21 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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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

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