Belnacasan | ICE/caspase-1 inhibitor

Belnacasan (273404-37-8) is a prodrug of VRT-043198, a potent (Ki = 0.8 nM ICE/caspase-1; <0.6nM caspase-4) and selective inhibitor of interleukin-converting enzyme/caspase-1 subfamily caspases.1 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 stress2 and prevention of glial pyroptosis in multiple sclerosis models3. It inhibited pyroptosis in vascular smooth muscle cells during atherogenesis suggesting a possible therapeutic effect in treating atherosclerotic disease.4 Belnacasan reduced acute seizures and drug resistant chronic epileptic activity in mice5 and provided neuroprotection in two rat models of temporal lobe epilepsy6.  It also displays protective effects in models of stroke7and Alzheimer’s disease8.

References:

  1. Wannamaker et al. (2007)(S)-1-((S)-2-{[1-(4-Amino-3-chlorophenyl)-methanoyl]-amino}-3,3-dimethylbutanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)-amide (VX-765), an Orally Available Selective Interleukin (IL)-Converting Enzyme/Caspase-1 Inhibitor, Exhibits Potent Anti-Inflammatory Activities by Inhibiting the Release of IL-1b and IL-18, Pharmacol. Exp. Ther. 321 509
  2. Zhang et al. (2015) NLRP3 Inflammasome Mediates Chronic Mild Stress-Induced Depression in Mice via Neuroinflammation, J. Neuropsychopharmacol. 18 pyv006
  3. McKenzie et al. (2018) Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis, Natl. Acad. Sci USA 115 E6065
  4. Li et al. (2020) VX-765 attenuates atherosclerosis in ApoE deficient mice by modulating VSMCs pyroptosis, Cell Res. 389 111847
  5. Maroso et al. (2011) Interleukin-1b biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice, Neurotherapeutics 8 304
  6. Noe et al. (2013) Pharmacological blockade of IL-1b/IL-1 receptor type 1 axis during epileptogenesis provides neuroprotection in two rat models of temporal lobe epilepsy, Dis. 59 183
  7. Li et al. (2019) Caspase-1 inhibition mediates neuroprotection in experimental stroke by polarizing M2 microglia/macrophage and suppressing NF-kB activation, Biophys. Res. Commun. 513 479
  8. Flores et al. (2018) Caspase-1 inhibition alleviates cognitive impairment in an Alzheimer’s disease mouse model, Commun. 9 3916
Weight 0.1 mg
Dimensions 0.1 × 0.1 × 0.1 cm
Size:

5 mg, 25 mg

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CAS:
273404-37-8
Catalog Number:
10-4399
Activity:
ICE/caspase-1 inhibitor
Chemical Names:
(S)-1-((S)-2-(4-Amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide; VX-765
Molecular Weight:
508.99
Molecular Formula:
C24H33ClN4O6
Solubility:
Soluble in DMSO (>25 mg/ml)
Physical Properties:
Off-white to white solid
Purity:
98% HPLC
NMR (Conforms)
Storage Temperature:
-20°C
Stability:
Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
Shipping Code:
RT

Belnacasan | ICE/caspase-1 inhibitor

$45.00$160.00

CAS:
273404-37-8
Catalog Number:
10-4399
Activity:
ICE/caspase-1 inhibitor
Chemical Names:
(S)-1-((S)-2-(4-Amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide; VX-765
Molecular Weight:
508.99
Molecular Formula:
C24H33ClN4O6
Solubility:
Soluble in DMSO (>25 mg/ml)
Physical Properties:
Off-white to white solid
Purity:
98% HPLC
NMR (Conforms)
Storage Temperature:
-20°C
Stability:
Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
Shipping Code:
RT
  • 5 mg
  • 25 mg
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