AMG-458 is a potent, selective and orally bioavailable c-Met inhibitor, with Ki values of 1.2 nM and 2.0 nM for human and mouse c-Met, respectively[1].
IC50 & Target[1]
human c-Met
1.2 nM (Ki)
mouse c-Met
2.0 nM (Ki)
V1092I
1.1 nM (Ki)
D1228H
2.2 nM (Ki)
M1250T
4.1 nM (Ki)
H1094R
0.5 nM (Ki)
Y1230H
4.5 nM (Ki)
VEGDR2
4100 nM (Ki)
体内研究 (In Vivo)
AMG-458 (orally, 30, 100 mg/kg) significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
NIH-3T3/TPR-Met model and U-87 MG human glioblastoma xenograft model[1].
Dosage:
10, 30, 100 mg/kg.
Administration:
Orally q.d. or b.i.d.
Result:
With an ED50 of ∼12 mg/kg and an ED90 of ∼ 34 mg/kg in NIH-3T3/TPR-Met model. With an ED50 of ∼16 mg/kg and an ED90 of ∼ 59 mg/kg in U-87 MG human glioblastoma xenograft model. Significantly inhibited tumor growth at 30 and 100 mg/kg q.d. and 30 mg/kg b.i.d. without adverse effect on body weight.
Animal Model:
Balb/c mouse and SD rat[1].
Dosage:
1 mg/kg (Pharmacokinetic Analysis).
Administration:
IV dose: 1 mg/kg (20% Captisol with pH adjusted to 3.5 using methanesulfonic acid).
Result:
Exhibited CL ((L/h)/kg) values of 0.16 and 0.73, Vss (L/kg) values of 0.31 and 0.62, t1/2 (h) values of 1.3 and 1.0 in mouse and rat, respectively.
分子量
539.58
Formula
C30H29N5O5
CAS 号
913376-83-7
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Longbin Liu, 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-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458). J Med Chem. 2008 Jul 10;51(13):3688-91.
