1. Apoptosis
  2. Caspase
  3. Belnacasan

Belnacasan  (Synonyms: VX-765)

目录号: HY-13205 纯度: 99.99%
COA 产品使用指南

Belnacasan (VX-765) 是 VRT-043198 的口服生物活性前体,VRT-043198 是有效选择性的 IL 转换酶 (ICE)/caspase-1 抑制剂,对 caspase-1Ki 值为 0.8 nM,对 caspase-4 的 Ki 值小于 0.6 nM。Belnacasan (VX-765) 作用于外周血单核细胞,可抑制 LPS 诱导的 IL-1β 和 IL-18 释放,IC50 约为 0.7 μM。

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Belnacasan Chemical Structure

Belnacasan Chemical Structure

CAS No. : 273404-37-8

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规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥918
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5 mg ¥820
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10 mg ¥1100
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25 mg ¥2200
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50 mg ¥3580
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100 mg ¥5859
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200 mg   询价  
500 mg   询价  

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Top Publications Citing Use of Products

MCE 顾客使用本产品发表的 82 篇科研文献

WB

    Belnacasan purchased from MCE. Usage Cited in: J Leukoc Biol. 2019 Feb;105(2):401-410.  [Abstract]

    PMA-differentiated CASP4/5-deficient THP-1 cells are primed with 100 ng/mL LPS for 4 h, and are then left uninfected or are infected with S. Typhimurium (MOI 25, log-phase), in the presence of 25 μM VX765 to suppress cell death and cellular release of the ASC speck.

    Belnacasan purchased from MCE. Usage Cited in: Toxicology. 2018 Dec 1;410:26-40.  [Abstract]

    HUVECs are primed with 1 μg/mL LPS for 2 h, and then pretreated with or without 5 μM VX-765 for 1 h; following by treatment with Acrolein (50 μM) for 24 h. Western blot is performed to determine the expression of cleaved caspase-1, IL-1β and IL-18.

    Belnacasan purchased from MCE. Usage Cited in: Brain Behav Immun. 2017 Oct;65:99-110.  [Abstract]

    VX765 treatment successfully inhibits the caspase 1 activity and reduces nuclear TDP-43 and cleaved caspase-3 protein levels in the hippocampus of BDE-47-treated mice.

    Belnacasan purchased from MCE. Usage Cited in: Brain Behav Immun. 2016 Aug;56:175-86.  [Abstract]

    The effects of NLRP3 inflammasome inhibitor VX-765 on NF-κB and CD11b levels in Sham and OVX groups. Sham operation or bilateral ovariectomy is performed and then the mice are subcutaneously administrated with the chemicals as indicated for four weeks. (A) p-p65 protein level with representative protein bands presented on top of histogram; (B) CD11b protein level with representative protein bands presented on top of histogram.
    • 生物活性

    • 实验参考方法

    • 纯度 & 产品资料

    • 参考文献

    生物活性

    Belnacasan (VX-765) is an orally bioactive proagent of VRT-043198, which is a potent and selective inhibitor of IL-converting enzyme (ICE)/caspase-1 with Kis of 0.8 nM and less than 0.6 nM for caspase-1 and caspase-4, respectively. Belnacasan (VX-765) inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC50 of ~0.7 μM[1][2].

    IC50 & Target[1]

    Caspase-1

     

    体内研究
    (In Vivo)

    Belnacasan reduces inflammatory response in murine models of inflammatory disease[1].
    Belnacasan (50-200 mg/kg) significantly reduces serum IL-1β levels by as much as 60%. It is noteworthy that the effect of Belnacasan on the release of IL-1β induced by LPS reached a plateau at 100 mg/kg. Belnacasan (25-100 mg/kg × 2) significantly reduces ear edema. Belnacasan also dose-dependently reduces the concentrations of cytokines, chemokines, and inflammatory mediators in the ear biopsy samples[2].
    Belnacasan (25-200 mg/kg) significantly delays the time to seizure onset by 1.5- to twofold (p<0.01), reduces the number of seizures by 40% (p<0.01) and the total time spent in EEG seizure activity by 30 to 50% (p<0.01)[3].

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

    Clinical Trial
    分子量

    509.00

    Formula

    C24H33ClN4O6

    CAS 号
    性状

    固体

    颜色

    White to off-white

    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 (196.46 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响,请使用新开封的 DMSO)

    H2O 中的溶解度 : 1 mg/mL (1.96 mM; 超声助溶 (<60°C))

    配制储备液
    浓度 溶剂体积 质量 1 mg 5 mg 10 mg
    1 mM 1.9646 mL 9.8232 mL 19.6464 mL
    5 mM 0.3929 mL 1.9646 mL 3.9293 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。

    * 备注:如您选择水作为储备液,请稀释至工作液后,再用 0.22 μm 的滤膜过滤除菌后使用。

    • 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: 15% Cremophor EL    85% Saline

      Solubility: 3.33 mg/mL (6.54 mM); 澄清溶液; 超声助溶

    • 方案 二

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

      Solubility: ≥ 2.5 mg/mL (4.91 mM); 澄清溶液

      此方案可获得 ≥ 2.5 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 25.0 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。

    以下溶解方案,请直接配置工作液。建议现用现配,在短期内尽快用完。 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: 50% PEG300    50% Saline

      Solubility: 5 mg/mL (9.82 mM); 澄清溶液; 超声助溶

    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: 99.99%

    参考文献
    Kinase Assay
    [2]

    Enzyme inhibition is assayed by tracking of the rate of hydrolysis of an appropriate substrate labeled with either p-nitroaniline or aminomethyl coumarin (AMC) as follows: ICE/caspase-1, suc-YVAD-p-nitroanilide; caspase-4, Ac-WEHD-AMC; caspase-6, Ac-VEID-AMC; caspase-3, -7, -8, and -9, Ac-DEVD-AMC; and granzyme B, Ac-IEPD-AMC. Enzymes and substrates are incubated in a reaction buffer [10 mM Tris, pH 7.5, 0.1% (w/v) CHAPS, 1 mM dithiothreitol, and 5% (v/v) DMSO] for 10 min at 37°C. Glycerol is added to the buffer at 8% (v/v) for caspase-3, -6, and -9 and granzyme B to improve stability of enzymes. The rate of substrate hydrolysis is monitored using a fluorometer. Assays for cathepsin B and trypsin are performed[2].

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

    Cell Assay
    [1]

    A total of 2×105 cells/well (100 μL cell suspension) is distributed in triplicate in flat-bottom 96-well plates. Either 50 μL of Belnacasan (40 μM in RPMI 1640 complete medium containing 0.2% DMSO) or vehicle control is added to appropriate wells. Following a 30-min incubation at 37°C, 50 μL of LPS diluted in RPMI 1640 complete medium is added at final concentrations varying from 0.001 to 10 ng/mL. Cells are returned to a 37°C incubator. At 4 h after LPS addition, 75 μL of supernatant is removed from wells, cleared by centrifugation for 5 min at 1500 rpm, and stored at 4°C until assayed. Cells are returned to a 37°C incubator until 24 h after LPS addition, at which time 100 μL of supernatant is removed, cleared by centrifugation, and stored at 4°C. Supernatants are tested using ELISA kits for IL-1β, IL-6, IL-18, and IL-1α[1].

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

    Animal Administration
    [2][3]

    Mice[2]
    Single doses of Belnacasan (10, 21, 43, and 84 mg/kg) in vehicle (25% Cremophor EL in water) are administered via oral gavage. Blood samples (approximately 0.25-0.3 mL) are collected before dose administration and 0.167, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 h after dosing via the retroorbital sinus and processed for plasma. A high-performance liquid chromatography/mass spectrometry methodology is used to determine the concentration of Belnacasan and VRT-043198 in plasma samples. Noncompartmental analysis is carried out using WinNonlin Pro, version 4.0.1.
    Rats[3]
    Male Sprague-Dawley rats (250-280 g) are used. Belnacasan (25, 50, 200 mg/kg) is dissolved in 20% Cremophor and injected ip in rats once a day for 3 consecutive days. On the fourth day, rats receive Belnacasan, 45 min and 10 min before intrahippocampal injection of kainic acid. Respective controls are similarly injected with vehicle before kainic acid.

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

    参考文献

    Belnacasan 相关分类

    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
    H2O / DMSO 1 mM 1.9646 mL 9.8232 mL 19.6464 mL 49.1159 mL
    DMSO 5 mM 0.3929 mL 1.9646 mL 3.9293 mL 9.8232 mL
    10 mM 0.1965 mL 0.9823 mL 1.9646 mL 4.9116 mL
    15 mM 0.1310 mL 0.6549 mL 1.3098 mL 3.2744 mL
    20 mM 0.0982 mL 0.4912 mL 0.9823 mL 2.4558 mL
    25 mM 0.0786 mL 0.3929 mL 0.7859 mL 1.9646 mL
    30 mM 0.0655 mL 0.3274 mL 0.6549 mL 1.6372 mL
    40 mM 0.0491 mL 0.2456 mL 0.4912 mL 1.2279 mL
    50 mM 0.0393 mL 0.1965 mL 0.3929 mL 0.9823 mL
    60 mM 0.0327 mL 0.1637 mL 0.3274 mL 0.8186 mL
    80 mM 0.0246 mL 0.1228 mL 0.2456 mL 0.6139 mL
    100 mM 0.0196 mL 0.0982 mL 0.1965 mL 0.4912 mL

    * 备注:如您选择水作为储备液,请稀释至工作液后,再用 0.22 μm 的滤膜过滤除菌后使用。

    Help & FAQs
    • Do most proteins show cross-species activity?

      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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    产品名称:
    Belnacasan
    目录号:
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