AMG-458

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AMG-458 (AMG458) 是一种有效的、选择性的、口服生物可利用的 c-Met 抑制剂，Ki 为 1.2 nM。

AMG-458 (AMG458) is a potent, selective, orally bioavailable c-Met inhibitor with Ki of 1.2 nM (human c-Met); also potently binds to mutant c-Met (H1094R), c-Met (V1092I) and c-Met (D1228H) with Ki values of 0.5-2.2 nM; inhibits HGF-mediated c-Met phosphorylation in PC3 and CT26 cells with IC50 of 60 and 120 nM, abrogates the constitutive phosphorylation of c-Met in H441 cells; significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models.

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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. Animal Model:NIH-3T3/TPR-Met model and U-87 MG human glioblastoma xenograft model.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.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.

AMG458 | AMG 458

Angiogenesis

c-Met/HGFR

c-Met(D1228H)|c-Met(H1094R)|c-Met(Human)|c-Met(Mouse)|c-Met(V1092I)

Other Indications

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913376-83-7

539.592

C30H29N5O5

>98% (HPLC)

DMSO: 21 mg/mL (38.91 mM); Ethanol: <1 mg/mL; Water: <1 mg/mL （ < 1 mg/ml refers to the product slightly soluble or insoluble )

O=C(C1=C(C)N(CC(C)(O)C)N(C2=CC=CC=C2)C1=O)NC3=NC=C(OC4=CC=NC5=CC(OC)=CC=C45)C=C3

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

(-20℃)

With Ice Pack

≥ 2 years