Belnacasan, Caspase 1 (ICE) inhibitor (TBI4399)

Description

Product Details

Formal Name: (S)-1-((S)-2-(4-Amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide

Alternate Names: VX-765

Molecular Formula: C₂₄H₃₃ClN₄O₆

Formula Weight: 509.00

CAS Number: 273404-37-8

Purity: >98%

Formulation: powder

Solubility: Soluble in DMSO (up to 25 mg/ml)

Storage: -20°C

Stability: ≥ 1 year.

Applications

Caspase 1 (ICE) inhibitor

Functions

Belnacasan is a prodrug of VRT-043198 (O-desethyl-belnacasan), a potent (Ki = 0.8 nM ICE/caspase-1; <0.6nM caspase-4) and selective inhibitor of interleukin-converting enzyme/caspase-1 subfamily caspases. VRT-043198 ICE/caspase-1 IC50 = 0.67 µM PBMCs, 1.0 µM whole blood. It inhibited the release of IL-1b and IL-18 from human monocytes in vitro and their production in vivo in models of inflammation. Belnacasan inhibited the activation and expression of the NLRP3 Inflammasome leading to moderation of depressive-like behaviors induced by chronic mild stress and prevention of glial pyroptosis in multiple sclerosis models. It inhibited pyroptosis in vascular smooth muscle cells during atherogenesis suggesting a possible therapeutic effect in treating atherosclerotic disease. Belnacasan reduced acute seizures and drug resistant chronic epileptic activity in mice and provided neuroprotection in two rat models of temporal lobe epilepsy. It also displays protective effects in models of stroke and Alzheimer’s disease.

Application Procedures

First dissolved in DMSO (up to 25 mg/ml), then diluted to aqueous buffer. Solutions in DMSO may be stored at -20°C for up to 3 months.