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Purity: ≥98%
MLN-8054 (MLN8054), a benzazepine-based compound, is a selective, and ATP-competitive inhibitor of Aurora A kinase (AAK) with potential antitumor activity. It inhibits Aurora A kinase with an IC50 of 4 nM in Sf9 insect cells and shows >40-fold selectivity for Aurora A over Aurora B. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. MLN8054 was in Phase I clinical trials for advanced solid tumors.
ln Vitro |
MLN8054 is a reversible, ATP-competitive inhibitor of recombinant Aurora A kinase. When MLN8054 is compared to family member Aurora B, it is >40-fold more selective for Aurora A. In human tumor cells cultivated in vitro, MLN8054 preferentially inhibits Aurora A over Aurora B. Treatment with MLN8054 causes G2/M accumulation, spindle abnormalities, and suppresses proliferation in several types of cultured human tumor cells. With an IC50 range of 0.11 to 1.43 μM, MLN8054 efficiently suppresses the proliferation of cells originating from various tissue origins[1]. When human tumor cells are cultured with MLN8054, certain morphologic and biochemical alterations linked to senescence are observed[2].
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ln Vivo |
In vivo MLN8054 administration causes apoptosis, accumulation of mitotic cells, and inhibition of Aurora A[1]. At a dosage of 30 mg/kg, MLN8054 specifically inhibits the activity of Aurora A kinase. It has been demonstrated that MLN8054 inhibits Aurora A autophosphorylation in HCT116 tumor tissue at this dose and increases the levels of the Aurora B substrate, pHisH3[2].
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Animal Protocol |
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References |
[1]. Manfredi MG, et al. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4106-11.
[2]. Huck JJ, et al. MLN8054, an inhibitor of Aurora A kinase, induces senescence in human tumor cells both in vitro and in vivo. Mol Cancer Res. 2010 Mar;8(3):373-84 |
Molecular Formula |
C25H15CLF2N4O2
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Molecular Weight |
476.86
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CAS # |
869363-13-3
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Related CAS # |
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SMILES |
O=C(O)C1=CC=C(NC2=NC=C3C(C4=CC=C(Cl)C=C4C(C5=C(F)C=CC=C5F)=NC3)=N2)C=C1
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InChi Key |
HHFBDROWDBDFBR-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C25H15ClF2N4O2/c26-15-6-9-17-18(10-15)23(21-19(27)2-1-3-20(21)28)29-11-14-12-30-25(32-22(14)17)31-16-7-4-13(5-8-16)24(33)34/h1-10,12H,11H2,(H,33,34)(H,30,31,32)
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Chemical Name |
4-((9-chloro-7-(2,6-difluorophenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl)amino)benzoic acid.
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Synonyms |
MLN 8054; MLN-8054; MLN8054
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.24 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.36 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.36 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 15% Captisol:30mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0971 mL | 10.4853 mL | 20.9705 mL | |
5 mM | 0.4194 mL | 2.0971 mL | 4.1941 mL | |
10 mM | 0.2097 mL | 1.0485 mL | 2.0971 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00249301 | Terminated | Drug: MLN8054 | Breast Neoplasm Colon Neoplasm/td> | Millennium Pharmaceuticals, Inc. | October 2005 | Phase 1 |
NCT00652158 | Terminated | Drug: MLN8054 | Advanced Malignancies | Millennium Pharmaceuticals, Inc. | April 2006 | Phase 1 |
Low and high concentrations of MLN8054 result in cellular phenotypes consistent with Aurora A and Aurora B inhibition, respectively, and induce apoptosis.Proc Natl Acad Sci U S A.2007 Mar 6;104(10):4106-11. td> |
MLN8054 induces TGI in the HCT-116 colorectal and PC3 prostate tumor xenografts. MLN8054 results in inhibition of Aurora A and accumulation of mitotic cells after a single dose and apoptosis after repeat dosing in HCT-116 human tumor xenografts.Proc Natl Acad Sci U S A.2007 Mar 6;104(10):4106-11. td> |
MLN8054 selectively inhibits Aurora A over Aurora B in cultured human tumor cells.Proc Natl Acad Sci U S A.2007 Mar 6;104(10):4106-11. td> |