受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C24H33ClN4O6 |
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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) |
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* <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. |
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. |
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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. |
キナーゼアッセイ | Protease Enzyme Assays | |
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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. |
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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. |
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]
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。