Caspase-1 and Caspase-4 inhibitor
VX-765 | Unit size | Cat. code | Docs | Qty | Price |
---|---|---|---|---|---|
Caspase-1 and Caspase-4 inhibitor |
10 mg 50 mg |
inh-vx765i-1 |
Caspase-1 and Caspase-4 inhibitor
Casp-1 and Casp-4 inhibition by VX-765
VX-765 is a pro-drug converted by plasma esterases into an active peptidomimetic metabolite, VRT-043198, which potently inhibits caspase-1 and caspase-4 [1].
CASPASE-1 & CASPASE-4:
Both caspase-1 and caspase-4 belong to a family of inflammatory caspases that are crucial in regulating cell death and inflammation. Notably, inflammasome induction drives the self-cleavage and activation of caspase-1 which in turn leads to cleavage of the pro‑inflammatory cytokines interleukin-1 beta (IL-1β)/IL-18 and the pore-forming protein Gasdermin D (GSDMD) into their active forms. Additionally, the activation of the inflammasome also leads to alarmin secretion and pyroptosis, a form of immunogenic cell death.
MODE OF ACTION OF VX-765:
VX-765 acts by covalent modification of the catalytic cysteine residue in the active site of caspase-1. Through its inhibitory activity, it has been demonstrated that VX-765 reduces the production of IL-1β and IL-18 in models of inflammatory disease both in vitro and in vivo [1, 2]. In addition, it has been reported that this inhibitor blocks pyroptosis [3].
KEY FEATURES OF VX-765 :
- Upon conversion, a potent inhibitor of caspase-1 and caspase-4
- Each lot is highly pure (≥97%) and functionally tested
Read our review on inflammasomes.
References:
1. Wannamaker W. et al., 2007. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-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-1beta and IL-18. J Pharmacol Exp Ther. 321(2):509-16.
2. McKenzie B.A. et al., 2018. Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis. PNAS. 115(26):E6065-E6074.
3. Doitsh G. et al., 2014. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 505(7484):509-14.
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Specifications
CAS number: 273404-37-8
Chemical Name: (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide
Solubility: 100 mg/ml (200 mM) in DMSO or ethanol
Formula: C24H33ClN4O6
Molecular weight: 509 g/mol
Quality control
- Purity: ≥97% (UHPLC)
- The inhibitory activity of the product has been validated in inflammasome cellular assays using THP1-Null2 and HEK-Blue™ IL-1β cells.
- The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.
Contents
VX-765 (provided as a translucent film) is available in 2 quantities:
- 10 mg VX-765 (#inh-vx765-1)
- 5 x 10 mg VX-765 (#inh-vx765-5)
VX-765 is shipped at room temperature.
Upon receipt, store at -20°C.
Resuspended product is stable for at least 6 months when properly stored.
Avoid repeated freeze-thaw cycles.