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AMG-208

Cat. No. M1647
AMG-208 Structure
Size Price Availability Quantity
10mg USD 160 In stock
50mg USD 450 In stock
100mg USD 700 In stock
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Quality Control
Biological Activity

AMG 208 is a small molecule inhibitor of c-Met, which inhibits both ligand-dependent and ligand-independent c-Met activation, IC50 = 9.3 nM. The c-MET pathway is dysregulated in most human malignancies, and regulates tumor formation, progression and dissemination, and numerous c-MET pathway inhibitors are currently being evaluated in the clinic. AMG-208 shows the inhibition of HGF-mediated c-Met phosphorylation in PC3 cells with IC50 of 46 nM. Pre-incubation of AMG-208 with human liver microsomes for 30 minutes shows a potent time-dependent inhibition for CYP3A4 metabolic activity with IC50 of 4.1 μM, which is an eightfold decrease relative to the IC50 (32 μM) without preincubation.

Protocol
Cell Experiment
Cell lines PC-3 cells
Preparation method Cell-based autophosphorylation assay of c-Met.
IC50 measurements of compound activity on HGF-mediated c-Met autophosphorylation were determined in serum-starved PC-3 (human) cells using a quantitative electrochemiluminescent immunoassay. PC3 cells were plated at a density of 20,000 cells/well in 96 well-plates. 24 hours after plating, cells were starved in media containing 0.1% BSA for 18 to 20 hours. Cells were then treated with a 10-point serial dilution of Compound A for one hour at 37℃ followed by stimulation with optimal concentrations of recombinant human HGF for 10 minutes at 37℃. Cells were washed once with PBS and lysed (1% Triton X-100, 50 mM Tris pH 8.0, 100 mM NaCl, 300 µM Na3OV4 and protease inhibitors). Cell lysates were incubated with a biotin-labeled goat–anti-c-Met antibody (BAF358 – for human c-Met, R&D Systems, Minneapolis, MN) for capture followed by a mouse anti-phosphotyrosine antibody 4G10 (Upstate, Charlottesville, VA) and a BV-tagTM labeled anti-mouse IgG (BioVeris Inc., Gaithersburg, MD) as the detection antibody. Levels of c-Met phophorylation were then measured on a BioVeris M-Series instrument. The IC50 values are calculated using Xlfit4-parameter equation.
Concentrations IC50=46 nM
Incubation time 10 min
Animal Experiment
Animal models female Balb/c mice
Formulation 2%HPMC, 1%Tween80, in water adjusted to pH 2.2 with HCl
Dosages 3, 10, or 30 mg/kg
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 383.4
Formula C22H17N5O2
CAS Number 1002304-34-8
Purity >99%
Solubility DMSO
Storage at -20°C
References

Developing c-MET pathway inhibitors for cancer therapy: progress and challenges.
Liu et al. Trends Mol Med. 2010 Jan;16(1):37-45. PMID: 20031486.

Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase.
Albrecht BK, et al. J Med Chem. 2008 May 22;51(10):2879-82. PMID: 18426196.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: AMG-208 supplier, c-Met, inhibitors

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