Cat. No. Name Size Price Add Cart
KI1465AMG4585 mg$330
AMG45810 mg$624
AMG45850 mg$1896
AMG458200 mg$4828

Chemical Characteristic

Product NameAMG458
CAS No.913376-83-7
Molecular Weight 539.58
FormulaC30H29N5O5
Chemical Name1-(2-hydroxy-2-methylpropyl)-N-[5-(7-methoxyquinolin-4-yl)oxypyridin-2-yl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxamide
Smilesn1(n(c(=O)c(c1C)C(=O)Nc1ccc(cn1)Oc1ccnc2c1ccc(c2)OC)c1ccccc1)CC(C)(C)O
Chemical Structure

Biological activities

AMG458 is a novel selective c-Met inhibitor. The Ki of AMG458 is 1.2 and 2 nM against human and mouse c-Met, respectively.[1] AMG458 inhibits the phosphorylation of c-Met with an IC50 of 60 nM in a PC3 cell c-Met phosphorylation assay.[2] AMG458 reduces phospho-Met (p-Met) levels in both H441 and A549 cells. AMG458 enhances the radiosensitivity of H441 but not A549. AMG458 results in increased apoptosis in H441 but not in A549.[3] AMG458 yields a distinct spectrum of mutations rich in F1200 alterations.[4] AMG458 inhibits HGF-mediated c-Met phosphorylation with an ED90 of 30 mg/kg and an associated plasma exposure of 15 µM at 6 hours. AMG458 significantly prevents the growth of tumor in the NIH3T3/TPR-Met and U-87 MG xenograft models at 30 and 100 mg/kg q.d. and 30 mg/kg b.i.d. with no adverse effect on body weight.[1]

Protocols

In vitro: AMG458 is dissolved in DMSO.[3]

References

[1] Liu L, et al. Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: (2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridine -2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458). J Med Chem. 2008, 51(13): 3688-3691.
[2] Porter J. et al. Small molecule c-Met kinase inhibitors: a review of recent patents. Expert Opin Ther Pat. 2010, 20(2): 159-177.
[3] Li B, et al. Higher levels of c-Met expression and phosphorylation identify cell lines with increased sensitivity to AMG-458, a novel selective c-Met inhibitor with radiosensitizing effects. Int J Radiat Oncol Biol Phys. 2012, 84(4): e525-e531.
[4] Tiedt R, et al. A drug resistance screen using a selective MET inhibitor reveals a spectrum of mutations that partially overlap with activating mutations found in cancer patients. Cancer Res. 2011, 71(15): 5255-5264.

Please click here to fill online order form, and we will make sure to supply you product with detail information. This process usually takes between 24 to 48 hours, depending on products stock avaliability. All inquires and subsequent projects are handled in the strictest confidence and will be backed by a confidentiality agreement if required.
KareBayTM provides scientists and clinicians with a wide range of biotechnological products and science lab supplies for chemical research and analyzing life processes. KareBay's extensive capabilities include commercializing reagents and kits, manufacturing biotech products and providing contract research services to organizations worldwide. Our many global labs, offices, and business partners enable KareBay to extend its products and services to its customer base around the world.

Our products are used for research, laboratory and further evaluation purposes. They are not for human use.