Name: VX-765
Price: 236.00 USD

- Overview
  - Please contact us at for specific academic pricing.
    
    Background
    
    VX-765, an orally- absorbed pro-drug of VRT-043198, is a potent and selective inhibitor of caspase-1 which belongs to the ICE/caspase-1 sub-family caspases.
    Caspase-1, known as interleukin (IL)-1-converting enzyme, is responsible for the processing of a key inflammatory mediator IL-1β from an in active precursor to an active, secreted protein. In response to intracellular bacteria, caspase-1 is also reported to be involved in a rapid programme of cell death, termed pyroptosis in macrophages [1].
    VX-765 is usually metabolized to an active molecular VRT-043198. In cultures of peripheral blood mononuclear cells stimulated with bacterial products, VRT-043198 inhibited the release of Interleukin (IL)-1β and IL-18, but had no affect the secretion of other cytokines such as IL-α, TNFα, IL-6 and IL-8 [2].
    This product is also used in other models to illustrate the function of Caspase-1. Oral administration of VX-765 significantly reduced the severity of diseases and the inflammatory cytokines and chemokines secretion in the mouse model of rheumatoid arthritis and skin inflammation[1]. In addition, recent study demonstrated that VX-765 prevents CD4 T-cell pyroptotic death in a dose-dependent manner in HIV-infected lymphoid tissues [3].
    
    1. Denes A, Lopez-Castejon G, Brough D. Caspase-1: is IL-1 just the tip of the ICEberg Cell Death Dis 2012,3:e338.
    2. Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, et al. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoy l)-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 2007,321:509-516.
    3. Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 2014,505:509-514.
- Properties
  - Alternative Name
    
    (2S)-1-[(2S)-2-[(4-amino-3-chlorobenzoyl)amino]-3,3-dimethylbutanoyl]-N-[(2R,3S)-2-ethoxy-5-oxooxolan-3-yl]pyrrolidine-2-carboxamide
    
    CAS Number
    
    273404-37-8
    
    Molecular Formula
    
    C24H33ClN4O6
    
    Molecular Weight
    
    508.99
    
    Appearance
    
    A solid
    
    Purity
    
    98.00%
    
    Solubility
    
    insoluble in H2O; ≥313 mg/mL in DMSO; ≥50.5 mg/mL in EtOH with ultrasonic
    
    Storage
    
    Desiccate at -20°C
    
    * For Research Use Only
- Reference
  - 1. Hila Israelov, Orly Ravid, et al. "Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair." J Neuroinflammation 2020 Sep 9;17(1):267. PMID:32907600
    2. Darren C. Johnson, Marian C. Okondo, et al. "DPP8/9 inhibitors activate the CARD8 inflammasome in resting lymphocytes." Cell Death Dis. 2020 Aug 14;11(8):628. PMID:32796818
    3. Panina SB, Baran N, et al. "A mechanism for increased sensitivity of acute myeloid leukemia to mitotoxic drugs." Cell Death Dis. 2019 Aug 13;10(8):617. PMID:31409768
    4. Yang G, Wang J, et al. "White spot syndrome virus infection activates Caspase 1-mediated cell death in crustacean." Virology. 2018 Dec 13;528:37-47. PMID:30554072

VX-765

VX-765

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