Powder: -20°C for 3 years | In solvent: -80°C for 1 year
LY-411575 是一种高效的γ-secretase 抑制剂,能够抑制 Aβ40 蛋白的产生,在膜中的 IC50 为 0.078 nM,在细胞中为 0.082 nM。 它还抑制 Notch 切割,IC50 为 0.39 nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 338 | 现货 | ||
2 mg | ¥ 482 | 现货 | ||
5 mg | ¥ 822 | 现货 | ||
10 mg | ¥ 1,370 | 现货 | ||
25 mg | ¥ 2,320 | 现货 | ||
50 mg | ¥ 3,460 | 现货 | ||
100 mg | ¥ 4,920 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 869 | 现货 |
产品描述 | LY-411575, a potent γ-secretase inhibitor, is with IC50 of 0.078 nM in the membrane and 0.082 nM in cell-based. It also suppresses Notch clevage with IC50 of 0.39 nM. |
靶点活性 | Notch S3 cleavage:0.39 nM, γ secretase (cell-based):0.082 nM, γ secretase (membrane-based):0.078 nM |
体外活性 | LY-411575 inhibits γ-secretase which can be assessed by the substrates like amyloid precursor protein (APP) and Notch S3 cleavage. [1] LY-411575, which blocks Notch activation, results in apoptosis in primary and immortalized KS cells. [2] |
体内活性 | 10 mg/kg oral dose of LY-411575 decreases brain and plasma Aβ40 and -42 dose-dependently. [1] LY-411575 reduces cortical Aβ40 in young (preplaque) transgenic CRND8 mice (ED50 ≈ 0.6 mg/kg) and produces significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The therapeutic window is similar after oral and subcutaneous administration and in young and aged CRND8 mice. Both the thymus and intestinal side effects are reversible after a 2-week washout period. Three-week treatment with 1 mg/kg LY411575 reduces cortical Aβ40 by 69% without inducing intestinal effects, although a previously unreported change in coat color is observed. [3] |
激酶实验 | Assays for Aβ and NICD: Procedures for measuring γ-secretase activity in membranes prepared from HEK293 cells expressing APP have been described previously (Zhang L et al Biochemistry 40, 5049-5055). Intact HEK293 cells expressing either APP or NΔE are treated with various concentrations of LY- 411,575 for 4 hours at 37 °C. In the case of cells expressing NΔE, cells are lysed, the cell lysates are separated on a 4-12% NuPAGE gel, and the processed NICD fragment is detected via Western blot with a cleavage site-specific antibody. The inhibition of NICD production is quantified by spot densitometric analysis using FluorChem. In the case of cells expressing APP, the conditioned medium is collected, centrifuged at 10,000 × g for 5 minutes to remove cell debris, and stored at -20 °C prior to the determination of Aβ levels. Aβ40 and -42 produced in HEK293 membrane- and cell-based assays, as well as plasma Aβ40 and cortex Aβ40 from TgCRND8 mice, are analyzed without pretreatment using an electrochemiluminescence detection-based immunoassay. Plasma Aβ42 is measured by enzyme-linked immunosorbent assay. A commercially available enzyme-linked immunosorbent assay kit is used to measure cortex Aβ42 according to the manufacturer''s instructions. |
细胞实验 | DNA/PI staining is performed using standard methodologies. Briefly, 1 × 106 cells are permeabilized with 100% ethanol in the presence of 15% FBS. The cells are washed and then treated for 15 minutes at 37 °C with 10 mg/mL RNAse. PI (5 mg/mL) is added, and the cells incubated for 1 hour at 4 °C prior to analysis by flow cytometry with 10 000 cells analysed per gated determination. The results are confirmed using the Immunotech Annexin V staining kit following the manufacturers’ instructions. At least three independent experiments are performed showing similar results.</(Only for Reference) |
别名 | LY411575 |
分子量 | 479.48 |
分子式 | C26H23F2N3O4 |
CAS No. | 209984-57-6 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
H2O: < 1 mg/mL (insoluble or slightly soluble)
DMSO: 88 mg/mL (183.5 mM)
Ethanol: 11 mg/mL (22.9 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO / Ethanol | 1 mM | 2.0856 mL | 10.428 mL | 20.8559 mL | 52.1398 mL |
5 mM | 0.4171 mL | 2.0856 mL | 4.1712 mL | 10.428 mL | |
10 mM | 0.2086 mL | 1.0428 mL | 2.0856 mL | 5.214 mL | |
20 mM | 0.1043 mL | 0.5214 mL | 1.0428 mL | 2.607 mL | |
DMSO | 50 mM | 0.0417 mL | 0.2086 mL | 0.4171 mL | 1.0428 mL |
100 mM | 0.0209 mL | 0.1043 mL | 0.2086 mL | 0.5214 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。
LY-411575 209984-57-6 Apoptosis Neuroscience Proteases/Proteasome Stem Cells Gamma-secretase Inhibitor Gamma secretase γ-secretase Notch LY411575 LY 411575 inhibit inhibitor