All AbMole products are for research use only, cannot be used for human consumption.
Belnacasan (VX-765) is a novel and irreversible IL-converting enzyme/caspase-1 inhibitor with an IC50 of 0.8 nM. VRT-043198, a potent and selective inhibitor of ICE/caspase-1 sub-family caspases is an active metabolite VX-765. VRT-043198 exhibits 100-10,000-fold selectivity against other caspase-3 and -6-9. VX-765 was efficiently converted to VRT-043198 when administered orally to mice and inhibited LPS-induced cytokine secretion. VX-765 has been shown to inhibit acute partial seizures and has shown activity in models of chronic partial epilepsy that do not respond to currently available medicines for epilepsy.
In addition, VX-765 reduced disease severity and the expression of inflammatory mediators in models of rheumatoid arthritis and skin inflammation. Belnacasan reduces inflammatory response in murine models of inflammatory disease. Belnacasan (50-200 mg/kg) significantly reduces serum IL-1β levels by as much as 60%. It is noteworthy that the effect of Belnacasan on the release of IL-1β induced by LPS reached a plateau at 100 mg/kg.
J Clin Transl Hepatol. 2024;12(6):539-550.
Mitochondrial GRIM19 Loss Induces Liver Fibrosis through NLRP3/IL33 Activation via Reactive Oxygen Species/NF-кB Signaling
Belnacasan purchased from AbMole
Free Radic Biol Med. 2023 Mar 27;202:46-61.
Mitochondrial GRIM-19 loss in parietal cells promotes spasmolytic polypeptide-expressing metaplasia through NLR family pyrin domain-containing 3 (NLRP3)-mediated IL-33 activation via a reactive oxygen species (ROS) -NRF2- Heme oxygenase-1(HO-1)–NF–кB axis
Belnacasan purchased from AbMole
Arch Oral Biol. 2023 Feb 8;148:105642.
N-acetylcysteine protects human periodontal ligament fibroblasts from pyroptosis and osteogenic differentiation dysfunction through the SIRT1/NF-κB/Caspase-1 signaling pathway
Belnacasan purchased from AbMole
Front Oncol. 2021 Sep 24;11:728047.
Antidiabetic DPP-4 Inhibitors Reprogram Tumor Microenvironment That Facilitates Murine Breast Cancer Metastasis Through Interaction With Cancer Cells via a ROS–NF-кB–NLRP3 Axis
Belnacasan purchased from AbMole
EMBO Mol Med. 2020 Jan 9;12(1):e9386.
Glutathione peroxidase 8 negatively regulates caspase-4/11 to protect against colitis.
Belnacasan purchased from AbMole
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Source | EMBO Mol Med (2020 Jan). Figure 6. VX-765 (AbMole BioScience, Houston, TX, USA) |
| Method | intraperitoneal injections | |
| Cell Lines | male GPx8-/- mice | |
| Concentrations | 20 mg/kg | |
| Incubation Time | 14 days | |
| Results | Consistently, VX-765 treatment was also associated with lower mortality and less disease severity in mice with DSS-induced colitis. |
 |
Source | Brain Behav Immun (2016). Figure 7. VX-765 |
| Method | i.v. | |
| Cell Lines | C57BL/6 mice | |
| Concentrations | 25 mg/kg/day and 50 mg/kg/day | |
| Incubation Time | four weeks | |
| Results | As shown in Fig. 7A–B, with administration of VX-765 (25 mg/kg/day and 50 mg/kg/day), the mice showed decreased levels of mature IL-1b and IL-18 as compared to those with vehicle treatment (P < 0.01). |
 |
Source | Brain Behav Immun (2016). Figure 6. VX-765 |
| Method | i.v. | |
| Cell Lines | C57BL/6 mice | |
| Concentrations | 50 mg/kg/day | |
| Incubation Time | four weeks | |
| Results | Administration of VX-765 ameliorated depression- and anxiety-like behavior in OVX mice. VX-765 (50 mg/kg/day) significantly increased percentage of sucrose consumption in OVX mice as compared to vehicletreated OVX group. |
| Cell Experiment | |
|---|---|
| Cell lines | human PBMCs |
| Preparation method | 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 Belnacasan (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. |
| Concentrations | 40 μM |
| Incubation time | 4 h, 24 h |
| Animal Experiment | |
|---|---|
| Animal models | Collagen-Induced Arthritis Model in Mouse |
| Formulation | 25% Cremophor EL |
| Dosages | 10-100 mg/kg twice daily |
| Administration | oral gavage |
| Molecular Weight | 509.0 |
| Formula | C24H33ClN4O6 |
| CAS Number | 273404-37-8 |
| Solubility (25°C) | DMSO 90 mg/mL |
| Storage | Powder -20°C |
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Products are for research use only. Not for human use. We do not sell to patients.
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