AMG-337

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-337 是一种有效的选择性 MET 抑制剂，生化 IC50 为 1 nM；抑制 PC3 细胞中 HGF 介导的 MET 磷酸化。

AMG-337 is a potent and selective inhibitor of MET with biochemical IC50 of 1 nM; inhibits of HGF-mediated MET phosphorylation in PC3 cells; shows desirable preclinical pharmacokinetics, significant inhibition of MET phosphorylation in mice, and robust tumor growth inhibition in a MET-dependent mouse efficacy model.Gastric Cancer Phase 2 Clinical(In Vitro):AMG 337 (0-3 μM; 72 h) inhibits proliferation in MET-dependent cancer cell lines.AMG 337 (0-300 nM; 0-24 h; MKN-45, SNU-620, and SNU-5 cells) inhibits signaling through the PI3K and MAPK pathways in MET-amplified gastric cancer cell lines, resulting in an inhibition of MET-dependent cell proliferation and induction of apoptosis.(In Vivo):AMG 337 (0-30 mg/kg; p.o.; daily, for 28 d) inhibits MET signaling in tumor xenografts and inhibits tumor growth in MET-dependent tumor xenograft models.AMG 337 (0-3 mg/kg; p.o.; once, for 3 or 24 h) is associated with increased necrosis in the MET-dependent SNU-620 tumor xenograft model.

AMG 337 (0-3 μM; 72 h) inhibits proliferation in MET-dependent cancer cell lines.AMG 337 (0-300 nM; 0-24 h; MKN-45, SNU-620, and SNU-5 cells) inhibits signaling through the PI3K and MAPK pathways in MET-amplified gastric cancer cell lines, resulting in an inhibition of MET-dependent cell proliferation and induction of apoptosis. Apoptosis Analysis Cell Line:MKN-45 and SNU-620 cells Concentration:0, 3, 10, 30, 100 and 300 nM Incubation Time:24 hours Result:Increased the number of cells undergoing apoptosis.Cell Cycle Analysis Cell Line:MKN-45 and SNU-620 cells Concentration:0, 3, 10, 30, 100 and 300 nM Incubation Time:24 hours Result:Increased in a dose-dependent in cells in the G1 phase and with concurrent reduction of cells in S-phase.Western Blot Analysis Cell Line:MKN-45, SNU-620, and SNU-5 cells Concentration:100 nM Incubation Time:2 hours Result:Inhibited MET phosphorylation and phosphorylation of downstream effectors.Western Blot Analysis Cell Line:MKN-45, SNU-620, and SNU-5 cells Concentration:100 nM Incubation Time:24 hours Result:Induced PARP and caspase-3 cleavage in SNU-620 and SNU-5 cells.

AMG 337 (0-30 mg/kg; p.o.; daily, for 28 d) inhibits MET signaling in tumor xenografts and inhibits tumor growth in MET-dependent tumor xenograft models.AMG 337 (0-3 mg/kg; p.o.; once, for 3 or 24 h) is associated with increased necrosis in the MET-dependent SNU-620 tumor xenograft model. Animal Model:Female CD1 nu/nu mice bearing SNU-620, SNU-5, or U-87 MG xenografts Dosage:0, 0.3, and 1 mg/kg (SNU-620 xenograft); 0, 0.3, 1, 3, and 10 mg/kg (SNU-5 xenograft); 0, 3, 10 and 30 mg/kg (U-87 xenograft)Administration:Oral administration; daily, for 28 days Result:Inhibited tumor growth in MET-dependent tumor xenograft models.Animal Model:Female CD1 nu/nu mice bearing SNU-620, SNU-5, or U-87 MG xenograftsDosage:0.1, 0.5, 0.75, 1, 2, and 3 mg/kg Administration:Oral administration; once, for 3 hours Result:Inhibited Gab-1 phosphorylation in a dose-dependent manner.Animal Model:Female CD1 nu/nu mice with SNU-620 xenograft model (6-11 weeks of age; 20-26 g)Dosage:0, 0.3, 1, and 3 mg/kg Administration:Oral administration; once, for 3 or 24 hours Result:Increased immunohistochemical staining with anti-caspase-3 antibody and decreased immunohistochemical staining with anti-BrdU antibody.

AMG337 | AMG 337

Angiogenesis

c-Met/HGFR

Met|Met(H1094R)|Met(M1250T)|Met(V1092I)|Met(Y1230H)

Cancer

Gastric Cancer

1173699-31-4

463.4643

C23H22FN7O3

>98% (HPLC)

DMSO: ≥ 30 mg/mL

O=C1C2=C(N=CC(OCCOC)=C2)C=CN1[C@@H](C3=NN=C4C(F)=CC(C5=CN(C)N=C5)=CN43)C

1,6-Naphthyridin-5(6H)-one, 6-[(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-a]pyridin-3-yl]ethyl]-3-(2-methoxyethoxy)-

(-20℃)

With Ice Pack

≥ 2 years