Belnacasan

SKU: orb1301082

Description

Belnacasan

Research Area

Cell Biology, Protein Biochemistry

Key Properties

• CAS Number: 273404-37-8
• MW: 508.99
• Purity: 99.50%
• Formula: C₂₄H₃₃ClN₄O₆
• SMILES: CCO[C@@H]1OC(=O)C[C@@H]1NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)c1ccc(N)c(Cl)c1)C(C)(C)C
• Target: Caspase
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:9.3 mg/mL (18.27 mM);DMSO:240 mg/mL (471.52 mM);Ethanol:93 mg/mL (182.71 mM)

Bioactivity

• Target IC50:
  Caspase-4:< 0.6 nM (Ki)|Caspase-1:0.8 nM (Ki)
• 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.
• 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.
• Cell Research:
  VX-765 is solubilized in DMSO and stored, and then diluted with RPMI 1640 complete medium (DMSO 0.2%) before use. 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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Caspase-1, Caspase-4, Caspase, Belnacasan, Inhibitor, inhibit, VX765, VX-765, VX 765

Compound Identifiers

PubChem CID

11398092