Belnacasan (VX-765)

製品コードS2228 バッチS222809

印刷

化学情報

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.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (9.82mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.250mg/ml (2.46mM)	Taking the 1 mL working solution as an example, add 50 μL of 25 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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 K_i 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
キナーゼアッセイ	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/

+ 展开

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。