Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Semagacestat (LY450139) 是一种γ-secretase 抑制剂,抑制β-amyloid(Aβ42),Aβ38和Aβ40,IC50分别为 10.9,12 和 12.1 nM,可用于研究阿尔茨海默病。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 262 | 现货 | ||
2 mg | ¥ 369 | 现货 | ||
5 mg | ¥ 578 | 现货 | ||
10 mg | ¥ 1,080 | 现货 | ||
25 mg | ¥ 1,920 | 现货 | ||
50 mg | ¥ 3,730 | 现货 | ||
100 mg | ¥ 5,450 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 463 | 现货 |
产品描述 | Semagacestat (LY450139) (LY450139) is a γ-secretase blocker for Aβ42/Aβ40/Aβ38 (IC50: 10.9/12.1/12.0 nM) and also inhibits Notch signaling (IC50: 14.1 nM). |
靶点活性 | γ-secretase (Aβ40):12.1 nM, γ-secretase (Aβ38):12.0 nM, γ-secretase (Aβ42):10.9 nM |
体外活性 | Semagacestat reduces the secretion of Aβ42, Aβ40 and Aβ38 from H4 human glioma cells stably overexpressing human wild-type APP into the culture medium, with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, respectively, without affecting cell viability. Semagacestat also increases β-CTF in cell lysates with ECmax of 16.0 nM, and the increase can be unexpectedly attenuated at high concentrations. Semagacestat inhibits Notch signaling with IC50 of 14.1 nM, and shows minimal Notch-sparing selectivity with Notch IC50/Aβ42 IC50 only 1.3. [1] Semagacestat causes a concentration-dependent decrease in Aβ40 secreted into the medium with IC50 of 111 nM from murine CTX expressing endogenous murine APP, but murine Aβ42 formation in CTX is roughly 12-fold less than Aβ40 in accordance with data for neurons from wild type mice. [2] |
体内活性 | Oral administration of Semagacestat (1 mg/kg) to 5.5-month old APP-transgenic Tg2576 mice significantly ameliorates memory deficits on spatial working memory using the Y-maze task, which disappears after 8 days subchronic dosing. LY450139 decreases hippocampal levels of both Aβ42 and Aβ40 at 10 mg/kg (22-23% reduction) and 30 mg/kg (36-41% reduction) and increases β-CTF at 0.3-10 mg/kg in a dose dependent manner with no inhibition on the processing of other γ-secretase substrates, such as Notch, N-cadherin or EphA4, in the brain, but impairs normal cognition in wild-type mice and 3-month-old Tg2576 mice failing to restore cognitive deficits in the Y-maze test. [1] |
激酶实验 | Cellular APP processing assay and Notch signaling assay: H4 human glioma cells stably overexpressing human wild-type APP695 are treated with Semagacestat at various concentrations for 24 hours. Levels of Aβ42, Aβ40, and Aβ38 in the media are measured using separate ELISA kits. The expression vector of the constitutively active form of Notch (NotchΔE), encoding bases 1-60 and 5193-6657 of the human Notch1 coding region (NM_017617), is constructed into a pcDNA3.1 vector with a sequence modification from mouse to human. Notch signaling activity is evaluated using Cignal RBP-Jk Reporter Assay kit. RBP-Jk protein [CSL/CBF1/Su(H)/Lag1] is a transcription factor activated with Notch intracellular domain produced by γ-secretase. H4 cells are transiently transfected with the human NotchΔE expression vector and the RBP-Jk-responsive luciferase construct using Lipofectamine 2000, and then exposed to various concentrations of Semagacestat for 16 hours. Notch signaling is measured based on luciferase activity in the cell lysate using the Dual-Glo Luciferase Assay System. |
细胞实验 | Cells are incubated with Semagacestat for 24 hours. For detection of cell viability, the percentage of viable cells is quantified by their capacity to reduce 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) following incubation with 0.5 mg/mL MTT for 60 minutes. For the detection of sAPP species, cells are lysed and analysed by western blotting.(Only for Reference) |
别名 | LY450139, 塞美司他 |
分子量 | 361.44 |
分子式 | C19H27N3O4 |
CAS No. | 425386-60-3 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
H2O: < 1 mg/mL (insoluble or slightly soluble)
DMSO: 67 mg/mL (185.4 mM)
Ethanol: 39 mg/mL (107.9 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO / Ethanol | 1 mM | 2.7667 mL | 13.8336 mL | 27.6671 mL | 69.1678 mL |
5 mM | 0.5533 mL | 2.7667 mL | 5.5334 mL | 13.8336 mL | |
10 mM | 0.2767 mL | 1.3834 mL | 2.7667 mL | 6.9168 mL | |
20 mM | 0.1383 mL | 0.6917 mL | 1.3834 mL | 3.4584 mL | |
50 mM | 0.0553 mL | 0.2767 mL | 0.5533 mL | 1.3834 mL | |
100 mM | 0.0277 mL | 0.1383 mL | 0.2767 mL | 0.6917 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Semagacestat 425386-60-3 Neuroscience Proteases/Proteasome Stem Cells Beta Amyloid Gamma-secretase LY-450139 Inhibitor inhibit LY 450139 γ-secretase LY450139 β-amyloid peptide 塞美司他 Notch Gamma secretase Amyloid-β Abeta inhibitor