包装 | 价格(元) |
2mg | 电议 |
5mg | 电议 |
10mg | 电议 |
50mg | 电议 |
Cell experiment: | The cell viability is assessed using a tetrazolium salt (WST-8)-based colorimetric assay from the Cell Counting Kit 8 (CCK-8). The cells are seeded into 96-well plates at an initial density of 5×103 cells/well and cultured for 24 h, after which the cells are cultured with DMSO, increased concentrations of gefitinib or Avagacestat (BMS-708163) , BIBW2992, or the combination of Avagacestat (BMS-708163) and BIBW2992 for an additional 48 h. The A450 is measured in a microplate reader after 10 μL of CCK-8 solution is added and incubated for 1 h. The percentage of growth is shown relative to untreated controls. |
Animal experiment: | Four- to six-week-old female Balb/c athymic (nu + /nu +) mice are anesthetized with ether. The mice are acclimatized for one week before being injected with 1.5×106 PC9/AB2 cells that have been resuspended in 200 μL of matrigel. When established tumors of approximately 150-300 mm3 in diameter are detected, the mice are randomly divided into groups and fed orally by gavage with either vehicle (1% methylcellulose, 0.2% Tween 80 in sterilized water), gefitinib (3 mg/kg diluted in vehicle), Avagacestat (BMS-708163) (10 mg/kg diluted in vehicle), or a combination of gefitinib (3 mg/kg) and Avagacestat (BMS-708163) (10 mg/kg) for 5 days/week. Each treatment group consists of eight mice. The tumor volume are measured and calculated every five days using the following formula: π/6×(larger diameter)×(smaller diameter)2. After 30 days, mice are killed by cervical dislocation. |
产品描述 | BMS-708163 is a potent selective and orally bioavailable inhibitor of γ-secretase with IC50 value of 0.3nM [1]. The cleavage of amyloid precusor protein APP by γ-secretase causes the production of Aβ40 and Aβ42, which are cytotoxic and cause AD. In vitro assay shows BMS-708163 inhibits the formation of Aβ40 and Aβ42 in H4-8Sw cells. It also inhibits the human recombinant CYPs in vitro with IC50 value of 20μM. Notch receptor is another substrate of γ-secretase. The inhibition of Notch signal pathway results in some side effects. It is shown that the activity of BMS-708163 to inhibit Notch is 190-fold weaker than to APP. In female rats, oral administration of BMS-708163 significantly reduces the production of Aβ in plasma and brain at 10mg/kg and 100mg/kg. In addition, BMS-708163 also reduces Aβ in brain and CSF in male beagle dogs [1]. References: |