Belnacasan (VX-765)

製品コードS2228 バッチS222805

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H33ClN4O6
分子量 509 CAS No. 273404-37-8
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 100 mg/mL (196.46 mM)
Ethanol (warmed with 50ºC water bath) 100 mg/mL (196.46 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Belnacasan (VX-765) is a potent and selective inhibitor of caspase-1 with Ki of 0.8 nM in a cell-free assay. Phase 2.
in vitro

Belnacasan (VX-765) is an orally absorbed prodrug of VRT-043198, which exhibits potent inhibition against ICE/caspase-1 and caspase-4 with Ki of 0.8 nM and less than 0.6 nM, respectively. It also inhibits IL-1β release from both PBMCs and whole blood with IC50 of 0.67 μM and 1.9 μM, respectively. [1]
in vivo

Belnacasan (VX-765) inhibits LPS-induced IL-1β production by about 60% in a collagen-induced arthritis mouse model at 200 mg/kg, and results in a dose-dependent, statistically significant reduction in the inflammation scores and effective protection from joint changes. [1]

In vivo, it blocks kindling epileptogenesis in rats by preventing IL-1β increase in forebrain astrocytes without significant effect on afterdischarge duration. [2]

In the mouse model of acute seizures, this compound (50 mg/kg-200 mg/kg) produces the anticonvulsant effect by delaying the time to onset of the first seizure and decreasing the number of seizures as well as their total duration by average 50% and 64%. [3]

In adult rats with genetic absence epilepsy (GAERS), after the 3rd drug injection, it significantly reduces the cumulative duration and number of spike-and-wave discharges (SWDs) by 55% on average by selectively blocking IL-1β biosynthesis. [4]
特徴 A potent and selective inhibitor of interleukin-converting enzyme/caspase-1.

プロトコル(参考用のみ)

キナーゼアッセイ Protease Enzyme Assays
Belnacasan (VX-765) 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) dimethyl sulfoxide] for 10 minutes 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.
細胞アッセイ 細胞株 PBMCs
濃度 0.7 µM
反応時間 30 minutes
実験の流れ

Before exposure to LPS, PBMCs were pre-treated for 30 minutes with Belnacasan (VX-765).
動物実験 動物モデル Collagen-induced arthritis mouse model.
投薬量 ≤200 mg/kg
投与方法 Administered via p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/17289835/
  • https://pubmed.ncbi.nlm.nih.gov/18632279/
  • https://pubmed.ncbi.nlm.nih.gov/21431948/
  • https://pubmed.ncbi.nlm.nih.gov/21645619/
  • https://pubmed.ncbi.nlm.nih.gov/16081838/

カスタマーフィードバック

Data from [Data independently produced by , , Cell, 2018, 175(2):442-457]

Data from [Data independently produced by , , Mucosal Immunol, 2015, 10.1038/mi.2015.44]

Data from [Data independently produced by , , Mucosal Immunol, 2016, 9(1):124-36]

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長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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