Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Belnacasan (VX-765) 是一种 IL 转换酶 (ICE)/caspase-1 抑制剂,是 VRT-043198 的口服生物活性前药。Belnacasan 可以修饰 Caspase-1 的活性位点并导致 Caspase-1 阻断,从而与动物模型中炎症疾病的组织保护相关。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 276 | 现货 | ||
2 mg | ¥ 393 | 现货 | ||
5 mg | ¥ 647 | 现货 | ||
10 mg | ¥ 898 | 现货 | ||
25 mg | ¥ 1,780 | 现货 | ||
50 mg | ¥ 2,990 | 现货 | ||
100 mg | ¥ 3,850 | 现货 | ||
200 mg | ¥ 5,520 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 762 | 现货 |
产品描述 | Belnacasan (VX-765) is an IL-converting enzyme (ICE)/caspase-1 inhibitor and an orally bioactive prodrug of VRT-043198. Belnacasan modifies the active site of caspase-1 and leads to caspase-1 blockade, which has been associated with tissue protection against inflammatory diseases in animal models. |
靶点活性 | Caspase-4:<0.6 nM(Ki), Caspase-1:0.8 nM(Ki) |
体外活性 |
方法:人 PBMCs 和全血用 LPS 和 Belnacasan 处理 18 h,使用 ELISA 检测细胞因子。 结果:Belnacasan 抑制 PBMC 和全血的 IL-1β 释放,IC50 值为 0.67 µM 和 1.9 µM。[1] |
体内活性 |
方法:为测试体内活性,将 Belnacasan (25-200 mg/kg) 灌胃给药给 CD-1 小鼠,1 h 后静脉注射 LPS (2 mg/kg)。 结果:Belnacasan 在体内抑制 LPS 诱导的 IL-1β 产生。[1] 方法:为检测抗癫痫活性,将 Belnacasan (12.5-200 mg/kg) 腹腔注射给慢性癫痫 C57BL6 小鼠模型,每天两次,持续四天。 结果:Belnacasan 的反复全身给药以剂量依赖的方式显著降低了小鼠的慢性癫痫活动。[2] |
激酶实验 | 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]. |
细胞实验 | VX-765 is solubilized in DMSO and stored, and then diluted with RPMI 1640 complete medium (DMSO 0.2%) before use[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 VX-765 (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]. |
别名 | VX-765 |
分子量 | 508.99 |
分子式 | C24H33ClN4O6 |
CAS No. | 273404-37-8 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: 93 mg/mL (182.7 mM)
DMSO: 45 mg/mL (88.41 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
Ethanol / DMSO | 1 mM | 1.9647 mL | 9.8234 mL | 19.6468 mL | 49.1169 mL |
5 mM | 0.3929 mL | 1.9647 mL | 3.9294 mL | 9.8234 mL | |
10 mM | 0.1965 mL | 0.9823 mL | 1.9647 mL | 4.9117 mL | |
20 mM | 0.0982 mL | 0.4912 mL | 0.9823 mL | 2.4558 mL | |
50 mM | 0.0393 mL | 0.1965 mL | 0.3929 mL | 0.9823 mL | |
Ethanol | 100 mM | 0.0196 mL | 0.0982 mL | 0.1965 mL | 0.4912 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。
Belnacasan 273404-37-8 Apoptosis Proteases/Proteasome Caspase Inhibitor VX 765 VX765 inhibit VX-765 inhibitor