AMG-337 是一种口服有效的选择性 MET 激酶抑制剂，抑制 WT MET、H1094R MET、M1250T MET、HGF-stimulated pMET (PC3 细胞) MET、V1092I MET、Y1230H MET 和 D1228H MET 的IC50值分别为 1、1、4.7、5、21.5、1077 和 >4000 nM。AMG 337 在 MET 扩增的癌细胞系中抑制 MET 及其下游效应子的磷酸化，从而抑制 MET 依赖的细胞增殖和诱导凋亡 (apoptosis)。
| 生物活性 | AMG-337 is a potent, orally active, selectiveMETkinaseinhibitor withIC50values of 1, 1, 4.7, 5, 21.5, 1077 and >4000 nM of WTMET, H1094RMET, M1250TMET, HGF-stimulated pMET (PC3 cells)MET, V1092IMET, Y1230HMET, and D1228HMET, respectively. AMG 337 inhibits the phosphorylation ofMETand downstream effectors in MET-amplifiedcancercell lines, resulting in an inhibition of MET-dependent cell proliferation and induction ofapoptosis[1][2]. |
| IC50& Target | IC50: 1 (WT MET), 1 (H1094R MET), 4.7 (M1250T MET), 5 (HGF-stimulated pMET (PC3 cells) MET), 21.5 (V1092I MET), 1077 (Y1230H MET) and >4000 nM (D1228H MET)[1] |
体外研究
(In Vitro) | AMG 337 (0-3 μM; 72 h) inhibits proliferation in MET-dependent cancer cell lines[1].
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[1].
Apoptosis Analysis[1] | 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[1] | 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[1] | 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[1] | 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. |
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体内研究
(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[1].
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[1].
| Animal Model: | Female CD1 nu/nu mice bearing SNU-620, SNU-5, or U-87 MG xenografts[1] | | 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 xenografts[1] | | Dosage: | 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)[1] | | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(215.77 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.1577 mL | 10.7884 mL | 21.5768 mL | | 5 mM | 0.4315 mL | 2.1577 mL | 4.3154 mL | | 10 mM | 0.2158 mL | 1.0788 mL | 2.1577 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
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此方案可获得 ≥ 2.5 mg/mL (5.39 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (5.39 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.39 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (5.39 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.39 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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