1. Belnacasan

Belnacasan (Synonyms: VX-765)

目录号: HY-13205 纯度: 99.99%
产品使用指南

Belnacasan (VX-765) 是一种具有口服活性的 IL 转换酶 (ICE)/caspase-1 抑制剂,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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Size Price Stock Quantity
10 mM * 1 mL in DMSO ¥918 In-stock
5 mg ¥820 In-stock
10 mg ¥1100 In-stock
50 mg ¥3580 In-stock
100 mg ¥5859 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Top Publications Citing Use of Products

MCE 顾客使用本产品发表的科研文献

    Belnacasan purchased from MCE. Usage Cited in:

    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.

    Belnacasan purchased from MCE. Usage Cited in:

    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:

    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:

    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.
    • 生物活性

    • 实验参考方法

    • 技术信息

    • 纯度 & 产品资料

    • 参考文献

    Description

    Belnacasan (VX-765) is a orally active IL-converting enzyme (ICE)/caspase-1 inhibitor, which inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC50 of ~0.7 μM[1].

    IC50 & Target[1]

    Caspase-1

     

    In Vitro

    Belnacasan is an oral prodrug of VRT-043198. VRT-043198 is a potent and selective caspase-1 inhibitor with a Ki of 0.8 nM[1]. Belnacasan inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC50 of ~0.7 μM and reduces inflammatory response in murine models of inflammatory disease[1]. VBelnacasan is a potent, specific inhibitor of the caspase-1 subfamily[2].

    In Vivo

    Belnacasan doses 50, 100, and 200 mg/kg significantly (p<0.05) reduces serum IL-1β levels by as much as 60%, whereas 25 mg/kg has a smaller effect (~35% inhibition) that is not statistically significant. 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, 50, and 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 at doses of 25, 50, and 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].

    Clinical Trial
    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 27 mg/mL (53.05 mM)

    * "≥" means soluble, but saturation unknown。

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    10 mM 0.1965 mL 0.9823 mL 1.9646 mL
    * 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,并请注意储备液的保存方式和期限。
    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,配制前请先配制澄清的储备液,再依次添加助溶剂 (为保证实验结果的可靠性,体内实验的工作
    液,建议您现用现配,当天使用;澄清的储备液可以根据储存条件,适当保存;以下溶剂前的百分比是指该溶剂在您配制终溶液中的体积占比):

    • 1.

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

      Solubility: ≥ 2。08 mg/mL (4。09 mM); Clear solution

    • 2.

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

      Solubility: ≥ 2.08 mg/mL (4.09 mM); Clear solution

    • 3.

      请依序添加每种溶剂: 10% DMSO    90% corn oil

      Solubility: ≥ 2.08 mg/mL (4.09 mM); Clear solution

    *以上所有助溶剂都可在 MCE 网站选购。
    References
    • [1]。

      [2].

      [3].

    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.

    References
    • [1].

      [2]。

      [3]。

    Molecular Weight

    509.00

    Formula

    C₂₄H₃₃ClN₄O₆

    CAS No.

    273404-37-8

    SMILES

    ClC1=C(N)C=CC(C(N[C@@H](C(C)(C)C)C(N2[C@H](C(N[C@H]3CC(O[C@H]3OCC)=O)=O)CCC2)=O)=O)=C1

    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.99%

    • [1].

      [2].

      [3].

    • 摩尔计算器

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    × = ×
    C1   V1   C2   V2

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    产品名称:
    Belnacasan
    目录号:
    HY-13205
    需求量:

    Belnacasan

    Cat. No.: HY-13205

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