VX-765
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Cat.code:
inh-vx765i-1
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ABOUT
Caspase-1 and Caspase-4 inhibitor
VX-765 is a pro-drug converted by plasma esterases into an active peptidomimetic metabolite, VRT-043198, which potently inhibits the enzymes caspase-1 and caspase-4 [1]. Both caspase-1 and caspase-4 belong to a family of inflammatory caspases that are crucial in regulating cell death and inflammation [2, 3].
Mode of action:
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, 4]. In addition, it has been reported that this inhibitor blocks pyroptosis [5].
Key features:
- Upon conversion, a potent inhibitor of caspase-1 and caspase-4
- InvitroFit™ grade: each lot is highly pure (≥97%) and functionally tested
Download our Practical guide 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. Van Opdenbosch N. & Lamkanfi M. et al., 2019. Caspases in Cell Death, Inflammation, and Disease. Immunity. 50(6):1352-1364.
3. Tsuchiya K.et al., 2019. Caspase-1 initiates apoptosis in the absence of gasdermin D. Nat Commun. 10(1):2091. 4. 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.
5. Doitsh G. et al., 2014. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 505(7484):509-14.
All products are for research use only, and not for human or veterinary use.
InvitroFit™
InvitroFit™ is a high-quality standard specifically adapted for in vitro studies of inhibitors. InvitroFit™ products are highly pure (≥95%) and guaranteed free of bacterial contamination, as confirmed using HEK Blue™ TLR2 and HEK Blue™ TLR4 cellular assays. Each lot is rigorously tested for functional activity using validated (or proprietary) cellular models. This grade ensures reliability and reproducibility for your research applications.
SPECIFICATIONS
Specifications
C24H33ClN4O6
100 mg/ml (200 mM) in DMSO or ethanol
Negative (tested using EndotoxDetect™ assay)
In vitro Inflammasome cellular assays
Each lot is functionally tested and validated using cellular assays.
CONTENTS
Contents
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Product:VX-765
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Cat code:inh-vx765i-1
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Quantity:10 mg
VX-765 is provided as a translucent film.
Shipping & Storage
- Shipping method: Room temperature
- -20°C
- Avoid repeated freeze-thaw cycles
Storage:
Caution:
Details
Caspase-1 & Caspase-4:
Caspases are a family of cysteine proteases that are centrally involved in cell death and inflammatory responses [1, 2].
Notably, caspase-1, also known as interleukin-1 converting enzyme (ICE), plays a crucial role in the control of inflammation. Its activity is regulated by a multi-protein complex known as the inflammasome. Upon activation, caspase-1 processes interleukin-1β (IL-1β) and IL-18, and gasdermin D, promoting inflammation and pyroptosis, a form of cell death [1].
Caspase-4 is a 'non-canonical inflammasome' that senses intracellular lipopolysaccharide (LPS) from Gram-negative bacteria and causes an inflammatory response, independent of TLR4 [3,4]. Caspase-4 cannot cleave pro-IL-1β/pro-IL-18, but instead triggers the cleavage of the pore-forming protein gasdermin D, leading to the release of alarmins and K+ efflux from the cell. This ultimately induces the activation of canonical inflammasome response, through NLRP3, and caspase-1-mediated IL-1β/IL-18 maturation and secretion [3,4].
1. Van Opdenbosch N. & Lamkanfi M. et al., 2019. Caspases in Cell Death, Inflammation, and Disease. Immunity. 50(6):1352-1364.
2. Tsuchiya K.et al., 2019. Caspase-1 initiates apoptosis in the absence of gasdermin D. Nat Commun. 10(1):2091.
3. Schmid-Burgk J.L. et al., 2015. Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells. Eur. J. Immunol. 45:2911.
4. Baker P.J. et al., 2015. NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. Eur. J. Immunol. 45:2918.
Chemical structure of VX-765:
DOCUMENTS
Documents
Technical Data Sheet
Safety Data Sheet
Validation Data Sheet
Certificate of analysis
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