产品说明书

AMG-337

Print
Chemical Structure| 1173699-31-4 同义名 : -
CAS号 : 1173699-31-4
货号 : A103152
分子式 : C23H22FN7O3
纯度 : 99%+
分子量 : 463.464
MDL号 : MFCD29472283
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(226.55 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The MET receptor tyrosine kinase (RTK) plays a central role in regulating cell growth, survival, and invasion. Binding of hepatocyte growth factor (HGF) promotes MET dimerization, stimulating MET kinase activity. AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor. It potently inhibits the enzymatic activity of WT MET (IC50 = 1 nM) and a subset of MET mutants found in papillary renal cell carcinoma. AMG 337 also inhibits cell based HGF-induced MET phosphorylation in PC3 cells (IC50 = 5 nM). Competitive binding assays illustrated the selectivity of AMG 337, binding only MET when profiled against a diverse panel of 402 human kinases. AMG 337 inhibits proliferation in MET-dependent cancer cell lines following 72 hours of treatment with AMG 337. MET phosphorylation was completely inhibited in the gastric cancer cells lines MKN-45, SNU-620, and SNU-5 cells, following a 2-hour treatment with 100 nM AMG 337. In MKN-45 cells, 300 nM AMG 337 treatment for 24 hours resulted in a dose-dependent increase in cells in the G1 phase; with concurrent reduction of cells in S-phase. AMG 337 at a 0.5 mg/kg dose robustly inhibited Gab-1 (a kind of adaptor protein) phosphorylation, and escalation to 0.75 mg/kg or more resulted in >90% inhibition of MET signaling in the TPR-MET mouse tumor model [3].
作用机制 AMG 337 binds to a well-defined, inactive conformation of the MET activation loop (A-loop) in a binding mode .
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.79mL

2.16mL

1.08mL

21.58mL

4.32mL

2.16mL
参考文献

[1]Hughes PE, Rex K, et al. In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models. Mol Cancer Ther. 2016 Jul;15(7):1568-79.

[2]Cecchi F, Rabe DC, et al. Targeting the HGF/Met signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012 Jun;16(6):553-72.

[3]Hughes PE, Rex K, Caenepeel S, Yang Y, Zhang Y, Broome MA, Kha HT, Burgess TL, Amore B, Kaplan-Lefko PJ, Moriguchi J, Werner J, Damore MA, Baker D, Choquette DM, Harmange JC, Radinsky R, Kendall R, Dussault I, Coxon A. In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models. Mol Cancer Ther. 2016 Jul;15(7):1568-79. doi: 10.1158/1535-7163.MCT-15-0871. Epub 2016 Apr 19. PMID: 27196782.