BMS 794833

• 产品号: S2201
• CAS号: 1174046-72-0
• 分子式: C23H15ClF2N4O3
• 分子量: 468.8400064
• 保 存: -20°C

产品别名

• 标题: BMS 794833
• IUPAC标准名: N-{4-[(2-amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl}-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide
• IUPAC传统名: N-{4-[(2-amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl}-5-(4-fluorophenyl)-4-oxo-1H-pyridine-3-carboxamide
• 别名: BMS794833

产品登记号

• CAS号: 1174046-72-0

产品性质

• 作用靶点: c-Met
• 作用靶点: VEGFR
• 成盐信息: Free Base
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Cancer

Biological Activity

• Description: BMS794833 is a potent ATP competitive inhibitor of Met and VEGFR2 with IC50 of 1.7 nM and 15 nM, respectively.
• Targets: Met; VEGFR2
• IC50: 1.7 nM; 15 nM ^[1]
• In Vitro: BMS794833 also inhibits Met receptor activated gastric carcinoma cell line, GTL-16, with IC50 of 39 nM. ^[1]
• In Vivo: In GTL-16 human gastric tumor xenografts model, BMS798433 shows greater than 50% TGI for at least one tumor doubling time with no overt toxicity observed during 14 days. BMS798433 also shows complete tumor stasis at a dose of 25 mg/kg against U87 glioblastoma model. ^[1]
• Clinical Trials: BMS798433 is currently in Phase I clinical trial against advanced or metastatic solid tumor.

Protocol

• Protocol: Kinase Assay ^[1]
• Met kinase assay: BMS798433 is dissolved in DMSO and diluted by water before use. The reaction solution contains baculovirus expressed GST-Met kinase, 20 mM Tris-HCl (pH 7.4), 1 mM MnCl₂, 1 mM DTT, 0.1mg BSA, 0.1 mg polyGlu₄/tyr, 1μM ATP and 0.2μCi γ–ATP. Reactions are incubated at 30 °C for 1 hour and stopped by 8% TCA. TCA precipitates are collected onto GF/C plates using a universal harvester and the filters are quantitated using liquid scintillation counter.
• VEGFR2 assay: BMS798433 is dissolved in DMSO and diluted by water before use. The reaction solution contains 20 mM Tris-HCl (pH 7.4), 1 mM MnCl₂, 1 mM DTT, 0.1mg BSA, 75 μg polyGlu₄/tyr, 1μM ATP, 0.5 μCi γ–ATP and 7.5 ng/rxn enzyme stock (10% glycerol). The reaction is initiated by addition of enzyme and stopped by 30% TCA after 1 hour. Assays are prepared in 96 well plates and incubated at 27 °C for 1 hour. Then acid precipitated with TCA for 20 minutes on ice. Those precipitates are transferred to GF/C plates using a harvester and the filters are quantitated using liquid scintillation counter.
• Protocol: Cell Assay ^[1]
• Cell Lines: GTL-16 cells
• Concentrations: ~ 1 μM
• Incubation Time: 72 hours
• Methods: GTL-16 cells are seeded into 96 well plates and incubated for 24 hours. BMS798433 is dissolved in DMSO at 10 mM and diluted with culture medium before use. Then BMS798433 is added to the cells for 72 hours. After that, MTS assay is used to measure the IC50.
• Protocol: Animal Study ^[1]
• Animal Models: GTL-16 and U87 xenografts
• Doses: 25 mg/kg
• Administration: Orally once daily

References

• References: [1] WO2009094417A1

参考文献

• WO2009094417A1