Antibodies
MLN8054
- 貨號 Cat. No.
- S1100
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
MLN8054
MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM. It is more than 40-fold selective for Aurora A than Aurora B. Phase 1.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM. It is more than 40-fold selective for Aurora A than Aurora B. Phase 1. | |||||
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| Targets | Aurora A | |||||
| IC50 | 4 nM [1] | |||||
| 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] | |||||
| Features | ||||||
Protocol(Only for 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. |
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Cell Assay: [1]
| Cell lines | HCT-116, SW480, DLD-1, MCF-7, MDA-MB-231, Calu-6, H460, SKOV-3 and PC-3 cells |
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| 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. |
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| Dosages | ≤30 mg/kg |
| Administration | Administered via p.o. |
| Solubility | 15% Captisol, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00249301 | Terminated | Breast Neoplasm|Colon Neoplasm|Pancreatic Neoplasm|Bladder Neoplasm | Millennium Pharmaceuticals, Inc. | 2005-10 | Phase 1 |
| NCT00652158 | Terminated | Advanced Malignancies | Millennium Pharmaceuticals, Inc. | 2006-04 | Phase 1 |
Chemical Information
| Molecular Weight (MW) | 476.86 |
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| Formula | C25H15ClF2N4O2 |
| CAS No. | 869363-13-3 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 95 mg/mL (199 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| 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 Name | Benzoic acid, 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]- |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.47686 | 4.7686 | 9.5372 | 14.3058 |
Customer Reviews (3)
 Click to enlarge | Rating | |
| Source | Professora Dra. Maria Gabriela Rodrigues(DBA/FCUL).MLN8054 purchased from Selleck | |
| Method | oocyte developmental progress assay | |
| Cell Lines | oocytes | |
| Concentrations | 0-5 μM | |
| Incubation Time | 40 min | |
| Results | using MLN8054 compound, an Auroraâ€A inhibitor, decreases oocyte developmental progress and causes spindle anomalies. |
Product Citations (6)
Cdk activity couples epigenetic centromere inheritance to cell cycle progression. [Silva MC, et al. Dev Cell 2012;22(1):52-63]
Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG. [Foraker AB, et al. J Cell Biol 2012;198(4):591-605]
BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by βTrCP1. [Moustafa-Kamal M, et al. Cell Death Differ 2013;20(10):1393-403]
