AMG-458 is a potent c-Met inhibitor with a Ki of 1.2 nM, which is about 350 times more selective on c-Met than on VEGFR2.

 

Brand: BCM

 

Target: c-Met/HGFR

 

Signaling Pathways: Tyrosine Kinase/Adaptors

 

In Vitro: AMG 458 also inhibits HGF-mediated c-Met phosphorylation in PC3 and CT26 cells with IC50 of 60 and 120 nM. AMG 458 is observed to bind covalently to liver microsomal proteins from rats and humans in the absence of NADPH. AMG 458 is believed to react with thiol groups in proteins, producing a methoxy quinoline thioether conjugate. A recent study shows that the constitutive phosphorylation of c-Met in H441 is abrogated by AMG 458. The basal and HGF-induced phosphorylation of c-Met in A549 is attenuated by AMG 458. The combination of radiation therapy and AMG 458 treatment is found to synergistically increase apoptosis in the H441 cell line by reduction of p-Akt and p-Erk levels, but not in A549.

 

Solubility: Soluble in DMSO. Insoluble in Water; Insoluble in Ethanol.

 

Isomeric SMILES: CC1=C(C(=O)N(N1CC(C)(C)O)C2=CC=CC=C2)C(=O)NC3=NC=C(C=C3)OC4=C5C=CC(=CC5=NC=C4)OC  

 

InChIKey: GLBZSOQDAOLMGC-UHFFFAOYSA-N  

 

InChI: InChI=1S/C30H29N5O5/c1-19-27(29(37)35(20-8-6-5-7-9-20)34(19)18-30(2,3)38)28(36)33-26-13-11-22(17-32-26)40-25-14-15-31-24-16-21(39-4)10-12-23(24)25/h5-17,38H,18H2,1-4H3,(H,32,33,36)

 

Attribute
[Chem Name]	1-(2-hydroxy-2-methylpropyl)-N-[5-(7-methoxyquinolin-4-yl)oxypyridin-2-yl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxamide
[Synonym]	AMG-458; AMG458
[CAS No.]	913376-83-7
[MDL No.]	MFCD17169989
[Formula]	C30H29N5O5
[Molecular]	539.58
[Form]	Solid Powder
[Storage]	Sealed in dry. Stored at -20°C.

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