Belnacasan [273404-37-8]
Referência T6090-2mg
Tamanho : 2mg
Marca : TargetMol
Belnacasan [273404-37-8]
Belnacasan
(Synonyms: VX-765) Copy Product InfoBelnacasan (VX-765) is an orally active inhibitor of IL-converting enzyme/caspase-1.
Cas No. 273404-37-8
For research use only—not for human use. No sales to individuals. Use as intended only.
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Purity:99.5%
Color:White
COA HNMR HPLC
Product Information
Bioactivity
Chemical Properties
Storage & Solubility Information
| Description | Belnacasan (VX-765) is an orally active inhibitor of IL-converting enzyme/caspase-1. |
| Targets & IC50 | Caspase-1:0.8 nM (Ki), Caspase-4:< 0.6 nM (Ki) |
| In vitro | VX-765 demonstrates antiepileptic properties by preventing the increase of IL-1β in the forebrain astrocytes of rats, thereby inhibiting the occurrence of epilepsy without significantly affecting the duration of post-discharge. In adult rats with genetic absence epilepsy, a 3-day administration of VX-765 significantly reduces the cumulative duration and decreases the average spike-wave discharges by 55% through the selective blockade of IL-1β biosynthesis. In acute epileptic mouse models, doses ranging from 50 mg/kg to 200 mg/kg of VX-765 delay the onset of the first epileptic episode and reduce the average number of seizures by 50% and the total duration by 64%. Additionally, a 200 mg/kg dose in a collagen-induced arthritis mouse model suppresses 60% of lipopolysaccharide-induced IL-1β production and leads to a dose-dependent significant reduction in inflammation scores, effectively protecting against joint lesions. |
| In vivo | VRT-043198 inhibits the release of IL-1β from peripheral blood mononuclear cells (PBMCs) and whole blood, with IC50 values of 0.67 μM and 1.9 μM, respectively. VX-765, an orally bioavailable prodrug of VRT-043198, demonstrates potent inhibition of ICE/caspase-1 and caspase-4, with Ki values of 0.8 nM and <0.6 nM, respectively. |
| Synonyms | VX-765 |
| Kinase Assay | 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]. |
| Cell Research | 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]. |
| Molecular Weight | 508.99 |
| Formula | C24H33ClN4O6 |
| Cas No. | 273404-37-8 |
| Smiles | C([C@@H](NC(=O)C1=CC(Cl)=C(N)C=C1)C(C)(C)C)(=O)N2[C@H](C(N[C@@H]3[C@H](OCC)OC(=O)C3)=O)CCC2 |
| Relative Density. | 1.32 g/cm3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year Shipping with blue ice/Shipping at ambient temperature. | |||||||||||||||||||||||||||||||||||
| Solubility Information | Ethanol: 93 mg/mL (182.71 mM), Sonication is recommended. DMSO: 240 mg/mL (471.52 mM), Sonication is recommended.  | |||||||||||||||||||||||||||||||||||
| In Vivo Formulation | 10% DMSO+40% PEG300+5% Tween 80+45% Saline: 9.3 mg/mL (18.27 mM), Solution. Please add the solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately. The formulation provided above is for reference purposes only. In vivo formulations may vary and should be modified based on specific experimental conditions. | |||||||||||||||||||||||||||||||||||
Solution Preparation Table | ||||||||||||||||||||||||||||||||||||
Ethanol/DMSO
Note : The dilution table applies only to solid products. For liquid products, please calculate the stock solution based on the stated concentration and/or density. | ||||||||||||||||||||||||||||||||||||