Belnacasan (VX-765)

製品コードS2228 バッチS222808

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）
Clear solution
5% DMSO 40% PEG 300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. 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 Ki of 0.8 nM in a cell-free assay. Phase 2.
in vitro

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. And VRT-043198 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

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

In vivo, VX-765 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, VX-765 (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), VX-765, after the 3rd drug injection, 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
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

PBMCs were pre-treated with VX-765 for 30 minutes before exposure to LPS.
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.

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Selenium deficiency exacerbates ROS/ER Stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus [ Journal of Environmental Sciences, 2025, Volume 148] PubMed: none
Blocking CIRP protects against acute pancreatitis by improving mitochondrial function and suppressing pyroptosis in acinar cells [ Cell Death Discov, 2024, 10(1):156] PubMed: 38538578
Bacillus cereus cereolysin O induces pyroptosis in an undecapeptide-dependent manner [ Cell Death Discov, 2024, 10(1):122] PubMed: 38458999
Host E3 ubiquitin ligase ITCH mediates Toxoplasma gondii effector GRA35-triggered NLRP1 inflammasome activation and cell-autonomous immunity [ mBio, 2024, e0330223.] PubMed: 38376248
Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement [ Int J Oral Sci, 2024, 16(1):3] PubMed: 38221531
Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells [ Drug Resist Updat, 2023, 70:100985] PubMed: 37423117
Long-term exposure to house dust mites accelerates lung cancer development in mice [ J Exp Clin Cancer Res, 2023, 42(1):26] PubMed: 36670473
Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood-brain barrier function [ J Neuroinflammation, 2023, 10.1186/s12974-023-02938-z] PubMed: 37978545
Circulating extracellular vesicles from patients with traumatic brain injury induce cerebrovascular endothelial dysfunction [ Pharmacol Res, 2023, 192:106791] PubMed: 37156450
Regulatory T cells alleviate myelin loss and cognitive dysfunction by regulating neuroinflammation and microglial pyroptosis via TLR4/MyD88/NF-κB pathway in LPC-induced demyelination [ J Neuroinflammation, 2023, 20(1):41] PubMed: 36803990

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。