1. Neuronal Signaling Stem Cell/Wnt
  2. γ-secretase Amyloid-β Notch
  3. Semagacestat

Semagacestat  (Synonyms: LY450139)

目录号: HY-10009 纯度: 98.89%
COA 产品使用指南

Semagacestat 是一种 γ-secretase 抑制剂,抑制 β-amyloid (Aβ42),Aβ38Aβ40IC50 分别为 10.9,12 和 12.1 nM。也抑制 NotchIC50 为 14.1 nM。Semagacestat 可用于阿尔茨海默病的相关研究。

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Semagacestat Chemical Structure

Semagacestat Chemical Structure

CAS No. : 425386-60-3

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规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥560
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1 mg ¥318
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5 mg ¥700
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10 mg ¥1300
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50 mg ¥4500
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100 mg ¥7500
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Top Publications Citing Use of Products

    Semagacestat purchased from MCE. Usage Cited in: EMBO Mol Med. 2017 Jul;9(7):950-966.  [Abstract]

    Turnover of endogenous CD74 P8 is inhibited by RO4929079 and BMS-906024. Cell lysate Western blot of A20 cells treated with GSIs is developed with In-1 antibody. MK-0752 and Semagacestat tests used the same control lane (0 nM).
    • 生物活性

    • 实验参考方法

    • 纯度 & 产品资料

    • 参考文献

    生物活性

    Semagacestat is a γ-secretase inhibitor, inhibits β-amyloid (Aβ42), Aβ38 and Aβ40 with IC50s of 10.9, 12 and 12.1 nM, respectively; also inhibits Notch signaling with IC50 of 14.1 nM. Semagacestat can be used for the research of alzheimer's disease[1].

    IC50 & Target

    IC50: 10.9 nM (Aβ42), 12 nM (Aβ38), 12.1 nM (Aβ40), 14.1 nM (Notch)[1]

    体外研究
    (In Vitro)

    Semagacestat (LY450139) reduces the secretion of Aβ42, Aβ40, and Aβ38 in 96-well-cultured media and increases β-CTF in cell lysates as expected, although this increase is unexpectedly attenuated at high concentrations[1].
    In cortical neurons (CTX), Semagacestat (LY450139) causes a concentration-dependent decrease in Aβ40 secreted into the medium with IC50 value 111 nM for Semagacestat. Semagacestat causes a concentration-dependent decrease in Aβ40 and Aβ42 secreted into the medium with an IC50 value of 126 and 130 nM, respectively[2].
    Semagacestat (3 Μm; for 4 days) exhibits no significant cell toxicity in Huh7 cells[5].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    体内研究
    (In Vivo)

    Semagacestat (LY450139) is found to decrease both Aβ42 and Aβ40 at 10 mg/kg (22-23% reduction;p<0.01) and increase β-CTF at 0.3-10 mg/kg in a dose-dependent manner (15-162% elevation; p<0.01 at 1-10 mg/kg)[1]. The γ-secretase inhibitor, Semagacestat (LY450139), a highly potent low molecular weight compound, significantly reduces β-amyloid (Aβ) levels in cell cultures permanently over-expressing APP and in both wildtype and transgenic APP-expressing mice. Three hours following p.o. dosing of 30 mg/kg Semagacestat levels of Aβ40 are reduced by 43% (unpaired t-test, p=0.002) in the brains of wildtype C57BL/6 mice compare with vehicle treated controls. Subcutaneous administration of Semagacestat (30 mg/kg) transiently decreases the amounts of Aβ40 in the dialysate with a maximum reduction in Aβ40 levels of 80% at 3 h post-dosing (p<0.001)[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Clinical Trial
    分子量

    361.44

    Formula

    C19H27N3O4

    CAS 号
    性状

    固体

    颜色

    White to off-white

    中文名称

    司马西特

    运输条件

    Room temperature in continental US; may vary elsewhere.

    储存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    溶解性数据
    In Vitro: 

    DMSO 中的溶解度 : ≥ 100 mg/mL (276.67 mM; 吸湿的 DMSO 对产品的溶解度有显著影响,请使用新开封的 DMSO)

    * "≥" means soluble, but saturation unknown.

    配制储备液
    浓度 溶剂体积 质量 1 mg 5 mg 10 mg
    1 mM 2.7667 mL 13.8336 mL 27.6671 mL
    5 mM 0.5533 mL 2.7667 mL 5.5334 mL
    查看完整储备液配制表

    * 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
    储备液的保存方式和期限:-80°C, 2 years; -20°C, 1 year。-80°C储存时,请在2年内使用, -20°C储存时,请在1年内使用。

    • 摩尔计算器

    • 稀释计算器

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    质量
    =
    浓度
    ×
    体积
    ×
    分子量 *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    浓度 (start)

    C1

    ×
    体积 (start)

    V1

    =
    浓度 (final)

    C2

    ×
    体积 (final)

    V2

    In Vivo:

    请根据您的 实验动物和给药方式 选择适当的溶解方案。

    以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:
    ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用
    以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

    • 方案 一

      请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 3 mg/mL (8.30 mM); 澄清溶液

      此方案可获得 ≥ 3 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;再向上述体系中加入 50 μL Tween-80,混合均匀;然后再继续加入 450 μL 生理盐水 定容至 1 mL

      生理盐水的配制:将 0.9 g 氯化钠,溶解于 ddH₂O 并定容至 100 mL,可以得到澄清透明的生理盐水溶液。
    • 方案 二

      请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 3 mg/mL (8.30 mM); 澄清溶液

      此方案可获得 ≥ 3 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中,混合均匀。

      20% SBE-β-CD in Saline 的配制(4°C,储存一周):2 g SBE-β-CD(磺丁基醚 β-环糊精)粉末定容于 10 mL 的生理盐水中,完全溶解至澄清透明。
    动物溶解方案计算器
    请输入动物实验的基本信息:

    给药剂量

    mg/kg

    动物的平均体重

    g

    每只动物的给药体积

    μL

    动物数量

    由于实验过程有损耗,建议您多配一只动物的量
    请输入您的动物体内配方组成:
    %
    DMSO +
    +
    %
    Tween-80 +
    %
    Saline
    如果您的动物是免疫缺陷鼠或者体弱鼠,建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。
    方案所需 助溶剂 包括:DMSO ,均可在 MCE 网站选购。 Tween 80,均可在 MCE 网站选购。
    计算结果
    工作液所需浓度 : mg/mL
    储备液配制方法 : mg 药物溶于 μL  DMSO(母液浓度为 mg/mL)。
    您所需的储备液浓度超过该产品的实测溶解度,以下方案仅供参考,如有需要,请与 MCE 中国技术支持联系。
    动物实验体内工作液的配制方法 : 取 μL DMSO 储备液,加入 μL  μL ,混合均匀至澄清,再加 μL Tween 80,混合均匀至澄清,再加 μL 生理盐水
    连续给药周期超过半月以上,请谨慎选择该方案。
    请确保第一步储备液溶解至澄清状态,从左到右依次添加助溶剂。您可采用超声加热 (超声清洗仪,建议频次 20-40 kHz),涡旋吹打等方式辅助溶解。
    纯度 & 产品资料

    纯度: 98.89%

    参考文献
    Kinase Assay
    [1]

    H4 human glioma cells stably overexpressing human wild-type APP695 are maintained in DMEM supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cells are cultured in 96- or 6-well plates overnight, and then treated with each drug (e.g., Semagacestat) at various concentrations for 24 h. Levels of Aβ1-42, Aβ1-40, and Aβ1-38 in the media are measured using separate ELISA kits. To quantify β-CTF, cells are lysed with RIPA buffer (25 mM Tris, 150 mM NaCl, 1% NP-40, 1% sodium deoxycholate, 0.1% SDS; pH 7.6) containing Complete protease inhibitor mixture and applied to a human β-CTF ELISA kit at 1:20 dilution. Aliquots of the cell lysate are also used for CellTiter-Glo Luminescent Cell Viability Assay. The cell lysate from the six-well plate is subjected to Western blot analysis[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    Murine cortical neurons (CTX) are isolated from day 14 to 16 foetal C57BL/6 mice. Briefly, dissociated neurons are plated on 100 μg/mL poly-L-lysine coated dishes at a density of 0.25×106 cells/cm2 (800000 cells/mL; 100 μL/well, 96-well plate) and cultured in Neurobasal medium supplemented with 2% B-27 supplement without antioxidants, 0.5 mM L-glutamine and 100 U/mL penicillin and 0.1 mg/mL streptomycin. Neurons are fed every third day by replacing half of the medium. The proportion of glia cells in the cultures is less than 10%, as assessed by an antibody against glia-fibrillary acidic protein. CTX are used at 6 days in vitro (DIV) after complete medium change and incubated with secretase inhibitors (e.g., Semagacestat) for 24 h. Neurons and cell medium are used at DIV 7. For detection of cell viability, the percentage of viable cells is quantified by their capacity to reduce MTT following incubation with 0.5 mg/mL MTT for 60 min. Viability is routinely measured after all in vitro pharmacological experiments[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice[1]
    Female Tg2576 mice expressing human APP695 with the Swedish mutation (K670N/M671L) are used. Male transgenic mice are procured and crossbred with female B6SJLF1/J mice. To identify drug effects on cognitive function, four different experiments are conducted. The objective of Experiment 1 is to elucidate acute and subchronic drug effects on cognitive deficits in Tg2576 mice. Each drug (Semagacestat, BMS-708163, and GSM-2) is orally administered to 5.5-month-old Tg2576 mice for 8 d. Y-maze tests are conducted to evaluate spatial working memory 3 h after administration on days 1 and 8. Vehicle-treated Tg2576 mice demonstrates significantly lower spontaneous alternation rates than WT mice in the Y-maze test, suggesting deficits in spatial working memory. On day 1, 1 mg/kg Semagacestat, 1 mg/kg BMS-708163, and 0.1-0.3 mg/kg GSM-2 significantly ameliorates these cognitive deficits (acute effects). On day 8, however, the GSI effects disappear, whereas GSM-2 retained its significant effects (subchronic effects). Mice are killed immediately after the Y-maze test on day 8, when hippocampal levels of Aβ42, Aβ40, and β-CTF are determined by ELISA.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    参考文献

    完整储备液配制表

    * 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
    储备液的保存方式和期限:-80°C, 2 years; -20°C, 1 year。-80°C储存时,请在2年内使用, -20°C储存时,请在1年内使用。

    可选溶剂 浓度 溶剂体积 质量 1 mg 5 mg 10 mg 25 mg
    DMSO 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
    15 mM 0.1844 mL 0.9222 mL 1.8445 mL 4.6112 mL
    20 mM 0.1383 mL 0.6917 mL 1.3834 mL 3.4584 mL
    25 mM 0.1107 mL 0.5533 mL 1.1067 mL 2.7667 mL
    30 mM 0.0922 mL 0.4611 mL 0.9222 mL 2.3056 mL
    40 mM 0.0692 mL 0.3458 mL 0.6917 mL 1.7292 mL
    50 mM 0.0553 mL 0.2767 mL 0.5533 mL 1.3834 mL
    60 mM 0.0461 mL 0.2306 mL 0.4611 mL 1.1528 mL
    80 mM 0.0346 mL 0.1729 mL 0.3458 mL 0.8646 mL
    100 mM 0.0277 mL 0.1383 mL 0.2767 mL 0.6917 mL
    Help & FAQs
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      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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