AMG-900 |
| Catalog No.GC13198 |
A selective pan-Aurora kinase inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 945595-80-2
Sample solution is provided at 25 µL, 10mM.
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AMG900 is a highly sensitive and orally bioavailable inhibitor of Aurora Kinase with IC50 values of 5 nmol/L.
AMG900 is an inhibitor of all three aurora kinase family members. It was founded through the discovery of a new class of ATP-competitive phtha-lazinamine small molecule inhibitors of aurora kinases. AMG900 inhibits autophosphorylation of aurora-A and aurora-B in tumor cells, and also aborts cell division without a prolonged mitosis arrest and finally results cell death. It can inhibit 26 different tumor cell lines proliferation, meanwhile, it also has the ability to enhance other aurora kinase inhibitors' effective. [1, 2]
AMG900 had been tested in animal level using mice models. Mice bearing established HCT116 tumors and orally delivery AMG900. Comparing to the vehicle group, the experiment groups delivery AMG900 with different concentration showed an obvious smaller tumor volume. These results revealed that AMG900 has the ability to significantly inhibit tumor growth.
References:
1. Payton, M., et al., Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res, 2010. 70(23): p. 9846-54.
2. Geuns-Meyer, S., et al., Discovery of N-(4-(3-(2-Aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4- (4-methylthiophen-2-yl)p hthalazin-1-amine (AMG 900), A Highly Selective, Orally Bioavailable Inhibitor of Aurora Kinases with Activity against Multidrug-Resistant Cancer Cell Lines. J Med Chem, 2015. 58(13): p. 5189-207.
| Kinase experiment [1]: | |
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Enzyme kinase assays |
Recombinant GST- or His-tagged aurora-A (TPX2), and aurora-B proteins were expressed using a baculovirus system and purified by affinity chromatography. AMG 900 activity was assessed using a standardized homogenous time-resolved fluorescence (HTRF) assay. Enzyme assays for 24 other kinases (aurora-C, p38α, TYK2, JNK2, JAK3, c-Met, VEGFR2, p38β, TIE-2, ABL (T315I), ERK1, BTK, JNK3, CDK5, PKAα, JNK1, p70S6K, PKBα, MSK1, LCK, SRC, IGFR, JAK2, and c-KIT) were done internally in a similar manner. Concentrations of enzyme, peptide substrate, and ATP in the reaction were optimized depending on the specific activity of the kinase and measured Km values for their corresponding substrates. AMG 900 was evaluated in a kinome competition binding assay (n = 353 unique kinases) by Ambit Biosciences. AMG 900 was initially screened at a single concentration of 1000 nM, and quantitative binding constants (Kd) were determined for each positive hit (< 20 percentage of control). |
| Cell experiment [1]: | |
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Cell lines |
Human colon carcinoma HCT116 cell line |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
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Reaction Conditions |
50 nM; 48 hrs |
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Applications |
AMG 900 time-dependently increased apoptosis through the induction of cleaved caspase-7. |
| Animal experiment [1]: | |
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Animal models |
Nude mice bearing HCT116 tumors |
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Dosage form |
3.75, 7.5 or 15 mg/kg; o.p.; 3, 6 or 9 hrs |
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Applications |
AMG 900 significantly inhibited HCT116 tumors in a dose-dependent manner. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Payton, M., et al., Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res, 2010. 70(23): p. 9846-54. | |
| Cas No. | 945595-80-2 | SDF | |
| Chemical Name | N-[4-[3-(2-aminopyrimidin-4-yl)pyridin-2-yl]oxyphenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine | ||
| Canonical SMILES | CC1=CSC(=C1)C2=NN=C(C3=CC=CC=C32)NC4=CC=C(C=C4)OC5=C(C=CC=N5)C6=NC(=NC=C6)N | ||
| Formula | C28H21N7OS | M.Wt | 503.58 |
| Solubility | ≥ 25.2 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9858 mL | 9.9289 mL | 19.8578 mL |
| 5 mM | 0.3972 mL | 1.9858 mL | 3.9716 mL |
| 10 mM | 0.1986 mL | 0.9929 mL | 1.9858 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
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.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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