Belnacasan (VX-765)

Catalog No.S2228 Batch:S222808

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Technical Data

Formula

C24H33ClN4O6
Molecular Weight 509 CAS No. 273404-37-8
Solubility (25°C)* In vitro DMSO 100 mg/mL (196.46 mM)
Ethanol 100 mg/mL (196.46 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 40% PEG 300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Belnacasan (VX-765) is a potent and selective inhibitor of caspase-1 with Ki of 0.8 nM in a cell-free assay. Phase 2.
Targets
Caspase-4 [1]
(Cell-free assay)		 Caspase-1 [1]
(Cell-free assay)
<0.6 nM(Ki) 0.8 nM(Ki)
In vitro

VX-765 is an orally absorbed prodrug of VRT-043198, which exhibits potent inhibition against ICE/caspase-1 and caspase-4 with Ki of 0.8 nM and less than 0.6 nM, respectively. And VRT-043198 also inhibits IL-1β release from both PBMCs and whole blood with IC50 of 0.67 μM and 1.9 μM, respectively. [1]
In vivo

In collagen-induced arthritis mouse model, VX-765 (200 mg/kg) inhibits LPS-induced IL-1β production by about 60%, and results in a dose-dependent, statistically significant reduction in the inflammation scores and effective protection from joint changes. [1]

In vivo, VX-765 blocks kindling epileptogenesis in rats by preventing IL-1β increase in forebrain astrocytes without significant effect on afterdischarge duration. [2]

In the mouse model of acute seizures, VX-765 (50 mg/kg-200 mg/kg) produces the anticonvulsant effect by delaying the time to onset of the first seizure and decreasing the number of seizures as well as their total duration by average 50% and 64%. [3]

In adult rats with genetic absence epilepsy (GAERS), VX-765, after the 3rd drug injection, significantly reduces the cumulative duration and number of spike-and-wave discharges (SWDs) by 55% on average by selectively blocking IL-1β biosynthesis. [4]
Features A potent and selective inhibitor of interleukin-converting enzyme/caspase-1.

Protocol (from reference)

Kinase Assay:

[1]
  • Protease Enzyme Assays

    Enzyme inhibition is assayed by tracking of the rate of hydrolysis of an appropriate substrate labeled with either p-nitroaniline or aminomethyl coumarin (AMC) as follows: ICE/caspase-1, suc-YVAD-p-nitroanilide; caspase-4, Ac-WEHD-AMC; caspase-6, Ac-VEID-AMC; caspase-3, -7, -8, and -9, Ac-DEVD-AMC; and granzyme B, Ac-IEPD-AMC. Enzymes and substrates are incubated in a reaction buffer [10 mM Tris, pH 7.5, 0.1% (w/v) CHAPS, 1 mM dithiothreitol, and 5% (v/v) dimethyl sulfoxide] for 10 minutes at 37 °C. Glycerol is added to the buffer at 8% (v/v) for caspase-3, -6, and -9 and granzyme B to improve stability of enzymes. The rate of substrate hydrolysis is monitored using a fluorometer
Cell Assay:

[5]
  • Cell lines

    PBMCs

  • Concentrations

    0.7 µM

  • Incubation Time

    30 minutes

  • Method

    PBMCs were pre-treated with VX-765 for 30 minutes before exposure to LPS.
Animal Study:

[1]
  • Animal Models

    Collagen-induced arthritis mouse model.

  • Dosages

    ≤200 mg/kg

  • Administration

    Administered via p.o.

Customer Product Validation

Data from [Data independently produced by , , Cell, 2018, 175(2):442-457]

Data from [Data independently produced by , , Mucosal Immunol, 2015, 10.1038/mi.2015.44]

Data from [Data independently produced by , , Mucosal Immunol, 2016, 9(1):124-36]

Data from [Data independently produced by , , Front Immunol, 2016, 7:536.]

Selleck's Belnacasan (VX-765) has been cited by 141 publications

Selenium deficiency exacerbates ROS/ER Stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus [ Journal of Environmental Sciences, 2025, Volume 148] PubMed: none
Blocking CIRP protects against acute pancreatitis by improving mitochondrial function and suppressing pyroptosis in acinar cells [ Cell Death Discov, 2024, 10(1):156] PubMed: 38538578
Bacillus cereus cereolysin O induces pyroptosis in an undecapeptide-dependent manner [ Cell Death Discov, 2024, 10(1):122] PubMed: 38458999
Host E3 ubiquitin ligase ITCH mediates Toxoplasma gondii effector GRA35-triggered NLRP1 inflammasome activation and cell-autonomous immunity [ mBio, 2024, e0330223.] PubMed: 38376248
Cistanche phenylethanoid glycosides induce apoptosis and pyroptosis in T-cell lymphoma [ Am J Cancer Res, 2024, 14(3):1338-1352] PubMed: 38590417
Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement [ Int J Oral Sci, 2024, 16(1):3] PubMed: 38221531
Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells [ Drug Resist Updat, 2023, 70:100985] PubMed: 37423117
Long-term exposure to house dust mites accelerates lung cancer development in mice [ J Exp Clin Cancer Res, 2023, 42(1):26] PubMed: 36670473
Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood-brain barrier function [ J Neuroinflammation, 2023, 10.1186/s12974-023-02938-z] PubMed: 37978545
Circulating extracellular vesicles from patients with traumatic brain injury induce cerebrovascular endothelial dysfunction [ Pharmacol Res, 2023, 192:106791] PubMed: 37156450

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.