AMG-458 is a potent and selective inhibitor of human and mouse c-Met with IC50 value of 1.2 nM and 2.0 nM respectively.
c-Met, also known as hepatocyte growth factor receptor, is a receptor tyrosine kinase that can be activated by hepatocyte growth factor/scatter factor (HGF/SF). It is a membrane protein which plays an essential role in embryonic development and wound healing.
Recent study investigated the effect of AMG-456 treatment on cell radiosensitizing response. The results showed that AMG-458 treatment enhanced radiosensitivity in H441 with higher levels of c-Met but not in A549 with lower expression of c-Met .
This component was also used in an animal model to study the role of c-Met in the development of tumor. For instance, orally administration of AMG-456 resulted in significant inhibition of tumor growth in /TPR-Met and U-87 MG xenograft models without any adverse effect on body weight .
1. Li B, Torossian A, Sun Y, Du R, Dicker AP, Lu B. 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:e525-531.
2. Liu L, Siegmund A, Xi N, Kaplan-Lefko P, Rex K, Chen A, et al. Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-meth yl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458). J Med Chem 2008,51:3688-3691.
|Storage||Store at -20°C|
|Synonyms||AMG 458; AMG458|
|Solubility||Soluble in DMSO|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Description||AMG 458 is a potent inhibitor of c-Met with a Ki value of 1.2 nM.|
|Targets||c-Met (H1094R)||c-Met (V1092I)||c-Met (Human)||c-Met (Mouse)||c-Met (D1228H)|
|IC50||0.5 nM(Ki)||1.1 nM(Ki)||1.2 nM(Ki)||2.0 nM(Ki)||2.2 nM(Ki)|