1. Cell Cycle/DNA Damage
    Epigenetics
  2. Aurora Kinase

AMG 900 

Cat. No.: HY-13253 Purity: 98.19%
Handling Instructions

AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor with IC50 of 5 nM, 4 nM and 1 nM for Aurora A, B and C, respectively.

For research use only. We do not sell to patients.

AMG 900 Chemical Structure

AMG 900 Chemical Structure

CAS No. : 945595-80-2

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 144 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
5 mg USD 130 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 226 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 706 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
100 mg USD 1198 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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View All Aurora Kinase Isoform Specific Products:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor with IC50 of 5 nM, 4 nM and 1 nM for Aurora A, B and C, respectively.

IC50 & Target[1]

Aurora A

5 nM (IC50)

Aurora B

4 nM (IC50)

Aurora C

1 nM (IC50)

In Vitro

AMG 900 inhibits the enzyme activity of all 3 aurora kinase family members with IC50 values of 5 nM or less. In HeLa cells, AMG 900 inhibits autophosphorylation of aurora-A and -B in a concentration-dependent manner. Treatment of HCT116 cells with 50 nM of AMG 900 for 48 hours resulted in polyploidy and suppresses the formation of colonies after cell replating. AMG 900 inhibits cell proliferation, with EC50 values ranging from 0.7 to 5.3 nM. Importantly, 4 of these AMG 900-sensitive cell lines (HCT-15, MES-SA-Dx5, 769P, and SNU449) are resistant to paclitaxel and other anticancer agents. AMG 900 inhibits p-histone H3 or induced polyploidy across all the cell lines tested irrespective of P-gp or BCRP status with uniform potency (IC50 or EC50 values ranging from 2 to 3 nM)[1].

In Vivo

AMG 900 exhibits significant antitumor activity in all 9 xenograft models tested (50%-97% TGI compared with the vehicle-treated control group, P<0.005, P<0.0005). Importantly, AMG 900 is active in the MES-SA-Dx5 (84% TGI, P<0.0001) and NCI-H460-PTX (66% TGI, P<0.0001) xenograft models that are resistant to either Docetaxel or Paclitaxel administered at their respective maximum tolerated doses. AMG 900 inhibits the activity of aurora-B in HCT116 tumors and suppresses the growth of multiple xenografts that represent diverse tumor types[1]. Treatment with AMG 900 at 15 mg/kg significantly inhibits p-Histone H3 in the G2M cell population in mouse bone marrow (upper panel) and cytokeratin positive COLO 205 tumor (lower panel) compared with vehicle-treated controls[2]. AMG 900 exhibits a low-to-moderate clearance and a small volume of distribution. Its terminal elimination half-life ranged from 0.6 to 2.4 h. AMG 900 is well-absorbed in fasted animals with an oral bioavailability of 31% to 107%. Food intake had an effect on rate (rats) or extent (dogs) of AMG 900 oral absorption[3].

References
Preparing Stock Solutions
Concentration Volume Mass 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
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

AMG 900 is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].

Different tumor cell lines including NCI-H460, MDA-MB231, MES-SA, NCI-H460 PTX, MDA-MB-231 PTX, MES-SA Dx5, and HCT-15. are treated with AMG 900 (0.5, 5.0, 50 nM) for 48 hours, washed twice with complete media, and cells are replated at a density of 5000 cells per well in drug-free complete media. Cells are grown until the DMSO control wells are confluent. Cells are stained with crystal violet dye, washed with distilled water, and imaged using a digital scanner[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2][3]

AMG 900 is formulated as a suspension in 2% HPMC, 1% Tween-80, at pH 2.2 (Mice)[2].
AMG 900 is formulated in 2% hydroxypropyl methylcellulose/1% Tween 80 in water, pH 2.2 for oral administration. The pH is adjusted with methanesulphonic acid (Rats)[3].

Mice[2]
Female athymic nude mice of approximately 14 weeks of age are used. Mice are injected subcutaneously with 2×106 COLO 205 cells in 100 μL of 50% matrigel. Mice with established tumors (approximately 200 mm3) are assigned into experimental groups (n=10 per group) and administered a single oral dose of vehicle or AMG 900 at 3.75, 7.5, and 15 mg/kg. Three hours after treatment tissue specimens (bone marrow, tumor, and skin) are collected from individual mice for pharmacodynamic and histological analysis. Blood plasma samples (50 μL) are collected from individual mice to determine the concentration of AMG 900 using quantitative methods. Excised tumors are divided in half for parallel flow and imaging based cytometric analyses.
Rats[3]
Effect of food intake on AMG 900 PK is evaluated in male rats and male dogs following a single oral dose of AMG 900 at 5 mg/kg (rats) or 2 mg/kg (dogs) in the oral formulation mentioned above. For the rats, food is removed ~16 h before dosing for the fasted group, although the fed group had free access to standard laboratory rodent chow throughout the study; food is returned to rats in the fasted group 2 h post-dose. All the dogs are fasted for ~16 h before dosing. Each dog in the fed group receive 350 g of moist food 1 h prior to dosing, and any remaining food is removed after 1 h. All the dogs are fed 2 h post-dose. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

503.58

Formula

C₂₈H₂₁N₇OS

CAS No.

945595-80-2

SMILES

CC1=CSC(C2=NN=C(C3=C2C=CC=C3)NC4=CC=C(C=C4)OC5=C(C=CC=N5)C6=CC=NC(N)=N6)=C1

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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AMG 900
Cat. No.:
HY-13253
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