Semagacestat
产品说明书
 |
同义名 : | LY450139 |
| CAS号 : | 425386-60-3 | |
| 货号 : | A892738 | |
| 分子式 : | C19H27N3O4 | |
| 纯度 : | 98% | |
| 分子量 : | 361.435 | |
| MDL号 : | MFCD25542369 | |
| 存储条件： |
Pure form Sealed in dry,2-8°C In solvent -20°C:3-6个月-80°C:12个月 |
|
| 溶解度 : |
DMSO: 105 mg/mL(290.51 mM)，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： |
0.5% methylcellulose+water 30 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 描述 | Semagacestat is a γ-secretase inhibitor with efficacy in multiple cellular and animal models, with IC50 values of 10.9nM, 12.1nM, 12nM, 14.1nM for secretion of Aβ42, Aβ40, Aβ38 and Notch, respectively, and EC50 value of 16nM forβ-CTF production. Exposure to Semagacestat at concentration ranging in 3.2, 16, 80, 2000, and 10,000 nM for 24 h led a concentration-dependent increase of β-CTF and α-CTF in H4 cells stably overexpressing human wild-type APP. It is regarded as a candidate drug for a causal therapy against Alzheimer's disease and showed blood-brain barrier permeability. Oral administration of semagacestat at dose of 1mg for 8 days significantly ameliorated spatial working memory deficits (shown by Y-maze) in Tg2576 mice (5.5-monthold) on day 1, but not on day 8. Both reduction of hippocampal Aβ42/Aβ40 by 22–23% and elevation of β-CTF by 162% could be observed in Tg2576 mice after dose of 10mg. A subcutaneous injection of semagacestat at dose of 5 mg/kg immediately after traumatic brain injury and once daily for 3 consecutive days post-traumatic brain injury attenuated neurotrauma and neurogenic acute lung injury in rats due to reducing the accumulation of hypertrophic microglia in the vicinity of the lesion. | ||
| 细胞研究 | |||||
|---|---|---|---|---|---|
| 细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
| African green monkey CV1 cells | Function assay | Inhibition of gamma-secretase expressed in african green monkey CV1 cells coexpressing Gal4 DNA-binding/transactivation domain assessed as inhibition of notch processing by luciferase reporter assay, IC50=0.31623 μM | 20056541 | ||
| CHO cells | Function assay | Inhibition of gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion after overnight incubation by ELISA, ED50=0.015 μM | 23713656 | ||
| human SH-SY5Y cells | Function assay | Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells, IC50=0.038 μM | 19694467 | ||
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
|
1 mM 5 mM 10 mM |
2.77mL 0.55mL 0.28mL |
13.83mL 2.77mL 1.38mL |
27.67mL 5.53mL 2.77mL |
| 参考文献 |
|---|