Home Tools

Cart

Belnacasan

Catalog No. T6090 CAS 273404-37-8

Synonyms: VX-765

Belnacasan (VX-765) is an orally active IL-converting enzyme/caspase-1 inhibitor.

All products from TargetMol are for Research Use Only. Not for Human or Veterinary or Therapeutic Use.

Belnacasan, CAS 273404-37-8

Pack Size	Availability	Price/USD
2 mg	In stock	$ 31.00
5 mg	In stock	$ 46.00
10 mg	In stock	$ 78.00
25 mg	In stock	$ 173.00
50 mg	In stock	$ 247.00
100 mg	In stock	$ 441.00
200 mg	In stock	$ 649.00
1 mL * 10 mM (in DMSO)	In stock	$ 51.00

Bulk Inquiry

Select Batch

Purity: 99.5%

Purity: 98.45%

Purity: 98.44%

Purity: 97.43%

Purity: 96.53%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	Belnacasan (VX-765) is an orally active IL-converting enzyme/caspase-1 inhibitor.
Targets&IC50	Caspase-1:0.8 nM(Ki), Caspase-4:<0.6 nM(Ki)
In vitro	VX-765 demonstrates antiepileptic properties by preventing the increase of IL-1β in the forebrain astrocytes of rats, thereby inhibiting the occurrence of epilepsy without significantly affecting the duration of post-discharge. In adult rats with genetic absence epilepsy, a 3-day administration of VX-765 significantly reduces the cumulative duration and decreases the average spike-wave discharges by 55% through the selective blockade of IL-1β biosynthesis. In acute epileptic mouse models, doses ranging from 50 mg/kg to 200 mg/kg of VX-765 delay the onset of the first epileptic episode and reduce the average number of seizures by 50% and the total duration by 64%. Additionally, a 200 mg/kg dose in a collagen-induced arthritis mouse model suppresses 60% of lipopolysaccharide-induced IL-1β production and leads to a dose-dependent significant reduction in inflammation scores, effectively protecting against joint lesions.
In vivo	VRT-043198 inhibits the release of IL-1β from peripheral blood mononuclear cells (PBMCs) and whole blood, with IC50 values of 0.67 μM and 1.9 μM, respectively. VX-765, an orally bioavailable prodrug of VRT-043198, demonstrates potent inhibition of ICE/caspase-1 and caspase-4, with Ki values of 0.8 nM and <0.6 nM, respectively.
Kinase Assay	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) DMSO] for 10 min 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. Assays for cathepsin B and trypsin are performed[2].
Cell Research	VX-765 is solubilized in DMSO and stored, and then diluted with RPMI 1640 complete medium (DMSO 0.2%) before use[1]. A total of 2×105 cells/well (100 μL cell suspension) is distributed in triplicate in flat-bottom 96-well plates. Either 50 μL of VX-765 (40 μM in RPMI 1640 complete medium containing 0.2% DMSO) or vehicle control is added to appropriate wells. Following a 30-min incubation at 37°C, 50 μL of LPS diluted in RPMI 1640 complete medium is added at final concentrations varying from 0.001 to 10 ng/mL. Cells are returned to a 37°C incubator. At 4 h after LPS addition, 75 μL of supernatant is removed from wells, cleared by centrifugation for 5 min at 1500 rpm, and stored at 4°C until assayed. Cells are returned to a 37°C incubator until 24 h after LPS addition, at which time 100 μL of supernatant is removed, cleared by centrifugation, and stored at 4°C. Supernatants are tested using ELISA kits for IL-1β, IL-6, IL-18, and IL-1α[1].

Synonyms	VX-765
Molecular Weight	508.99
Formula	C24H33ClN4O6
CAS No.	273404-37-8

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

Ethanol: 93 mg/mL (182.7 mM)

DMSO: 93 mg/mL (182.7 mM)

References and Literature

1. Wannamaker W, et al. J Pharmacol Exp Ther. 2007, 321(2), 509-516. 2. Ravizza T, et al. Neurobiol Dis. 2008, 31(3), 327-333. 3. Maroso M, et al. Neurotherapeutics. 2011, 8(2), 304-315. 4. Akin D, et al. Neurobiol Dis. 2011, 44(3), 259-269. 5. Teng J F, Mei Q B, Zhou X G, et al. Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer[J]. MLA . Cancers. 2020, 12(1): 194.

Citations

1. Zhao Q, Feng H, Yang Z, et al. The central role of a two‐way positive feedback pathway in molecular targeted therapies‐mediated pyroptosis in anaplastic thyroid cancer. Clinical and Translational Medicine. 2022, 12(2): e727 2. Zhao Q, Feng H, Yang Z, et al. The central role of a two‐way positive feedback pathway in molecular targeted therapies‐mediated pyroptosis in anaplastic thyroid cancer. Clinical and Translational Medicine. 2022, 12(2): e727 3. Teng J F, Mei Q B, Zhou X G, et al. Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer MLA. Cancers. 2020, 12(1): 193. 4. Hussain M, Lu Y, Tariq M, et al. A small-molecule Skp1 inhibitor elicits cell death by p53-dependent mechanism. Iscience. 2022, 25(7): 104591. 5. Xia H, Zhang Z, You F. Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection. Viruses. 2021, 13(12): 2383. 6. Li Y, Yang W, Zheng Y, et al.Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis.Journal of Experimental & Clinical Cancer Research.2023, 42(1): 1-19. 7. Liu M, Wang Y, Li S, et al.Attenuates reactive oxygen species: induced pyroptosis via activation of the Nrf2/HO-1 signal pathway in models of trigeminal neuralgia.Scientific Reports.2023, 13(1): 18111.

Related compound libraries

This product is contained In the following compound libraries：

Drug Repurposing Compound Library Inhibitor Library Anti-Cancer Drug Library Anti-Cancer Clinical Compound Library Anti-Cancer Compound Library Protease Inhibitor Library Bioactive Compounds Library Max Pyroptosis Compound Library Clinical Compound Library Immunology/Inflammation Compound Library

Related Products

Related compounds with same targets

Ac-DNLD-CHO PAC-1 Ac-AAVALLPAVLLALLAP-LEHD-CHO Quinovic acid VR23 3-O-trans-p-Coumaroyltormentic acid Crenulatin Isochamaejasmine

Dose Conversion

You can also refer to dose conversion for different animals. More

In vivo Formulation Calculator (Clear solution)

Step One: Enter information below

Dosage

mg/kg

Average weight of animals

Dosing volume per animal

Number of animals

Step Two: Enter the in vivo formulation

% DMSO+

% +

% Tween 80+

% ddH₂O

%DMSO+

Calculate Reset

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL)，Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation：Take μL DMSO master liquid, next add μL PEG300， mix and clarify, next add μL Tween 80，mix and clarify, next add μL ddH₂O, mix and clarify.

Note:

Be sure to add the solvent(s) in order. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Calculator

Molarity Calculator

Dilution Calculator

Reconstitution Calculation

Molecular Weight Calculator

Mass

Concentration

Volume

Molecular Weight

Molarity Calculator allows you to calculate the

Mass of a compound required to prepare a solution of known volume and concentration
Volume of solution required to dissolve a compound of known mass to a desired concentration
Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of a molarity calculation using the molarity calculator
What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol?
Enter 197.13 into the Molecular Weight (MW) box
Enter 10 into the Concentration box and select the correct unit (millimolar)
Enter 10 into the Volume box and select the correct unit (milliliter)
Press calculate
The answer of 19.713 mg appears in the Mass box

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Calculator the dilution required to prepare a stock solution

Calculate the dilution required to prepare a stock solution
The dilution calculator is a useful tool which allows you to calculate how to dilute a stock solution of known concentration. Enter C1, C2 & V2 to calculate V1.

See Example

An example of a dilution calculation using the Tocris dilution calculator
What volume of a given 10 mM stock solution is required to make 20ml of a 50 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=50 μM, V2=20 ml and V1 is the unknown:
Enter 10 into the Concentration (start) box and select the correct unit (millimolar)
Enter 50 into the Concentration (final) box and select the correct unit (micromolar)
Enter 20 into the Volume (final) box and select the correct unit (milliliter)
Press calculate
The answer of 100 microliter (0.1 ml) appears in the Volume (start) box

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Calculate the volume of solvent required to reconstitute your vial.

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial.
Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

Molecule Formula

Molecular Weight g/mol

Enter the chemical formula of a compound to calculate its molar mass and elemental composition

Tip: Chemical formula is case sensitive: C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed n the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

bottom

Tech Support

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

Belnacasan 273404-37-8 Apoptosis Proteases/Proteasome Caspase Inhibitor VX 765 VX765 inhibit VX-765 inhibitor

Products are chemical reagents for research use only and are not intended for human use. We do not sell to patients.