AMG-900

A selective pan-Aurora kinase inhibitor

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库存: 现货

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数量
5mg

￥937.00

750.00

- +
10mg

￥1612.00

1290.00

- +
50mg

￥4787.00

3830.00

- +
200mg

￥12312.00

9850.00

- +
500mg

￥30912.00

24730.00

- +
1g

￥43137.00

34510.00

- +

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Background

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.

参考文献:
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.

Protocol

Kinase experiment [1]:
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]:
Cell lines	Human colon carcinoma HCT116 cell line
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.
Reaction Conditions	50 nM; 48 hrs
Applications	AMG 900 time-dependently increased apoptosis through the induction of cleaved caspase-7.
Animal experiment [1]:
Animal models	Nude mice bearing HCT116 tumors
Dosage form	3.75, 7.5 or 15 mg/kg; o.p.; 3, 6 or 9 hrs
Applications	AMG 900 significantly inhibited HCT116 tumors in a dose-dependent manner.
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.
参考文献: [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.