VX-765 (Synonyms: Belnacasan; VX-765) |
رقم الكتالوجGC12725
One-Click Copy Product Info
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VX-765 is an orally available selective and competitive inhibitor of ICE/caspase-1 with an IC50 value of 3.68nM for caspase-1.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 273404-37-8
Sample solution is provided at 25 µL, 10mM.
VX-765 is an orally available selective and competitive inhibitor of ICE/caspase-1 with an IC50 value of 3.68nM for caspase-1[1]. VX-765 was efficiently converted to VRT-043198 when administered orally to mice, and inhibited lipopolysaccharide-induced cytokine secretion[2]. VX-765 has been widely employed to alleviate disease severity and the generation of inflammatory mediators in models of rheumatoid arthritis and skin inflammation[3].
In vitro, VX-765 pretreatment (10µM) for 12h significantly decreased the apoptosis and inflammatory responses induced by oxygen-glucose deprivation (OGD) in human umbilical mesenchymal stem cells (HUMSCs), and increased the AMPK/mTOR signaling pathway activity[4]. Treatment with VX-765 (5µM) for 24h attenuated oxidative stress and inflammatory responses induced by hypoxia-reoxygenation (H/R) in Caco-2 cells and decreased the levels of TNF-α, IL-6, and IL-1β[5].
In vivo, VX-765 treatment via oral administration at a dose of 50mg/kg/day for 6 weeks significantly attenuated the progression of atherosclerosis and suppressed the development of atherosclerotic plaques in ApoE−/− mice[6]. VX-765 was given by intraperitoneal injection (50mg/kg/day for 3 consecutive days), which significantly reduced the systemic inflammatory response induced by silica in mice and delayed the progression of pulmonary fibrosis[7]. Daily intraperitoneal injection of VX-765 at a dose of 100mg/kg for 8 weeks improved the renal function of diabetic mice, inhibited the infiltration of inflammatory cells and the expression of pyroptosis-related proteins, and mitigated renal tubulointerstitial fibrosis[8].
References:
[1] Flores J, Noël A, Foveau B, et al. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer’s disease mouse model[J]. Nature communications, 2018, 9(1): 3916.
[2] Stack J H, Beaumont K, Larsen P D, et al. IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patients[J]. The Journal of Immunology, 2005, 175(4): 2630-2634.
[3] Wannamaker W, Davies R, Namchuk M, et al. (S)-1-((S)-2-{[1-(4-Amino-3-chloro-phenyl)-methanoyl]-amino}-3, 3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2 R, 3 S)-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-1β and IL-18[J]. The Journal of pharmacology and experimental therapeutics, 2007, 321(2): 509-516.
[4] Sun Z, Gu L, Wu K E, et al. VX‐765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke‐induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway[J]. CNS neuroscience & therapeutics, 2020, 26(9): 952-961.
[5] Lyu H, Ni H, Huang J, et al. VX-765 prevents intestinal ischemia-reperfusion injury by inhibiting NLRP3 inflammasome[J]. Tissue and Cell, 2022, 75: 101718.
[6] Li Y, Niu X, Xu H, et al. VX-765 attenuates atherosclerosis in ApoE deficient mice by modulating VSMCs pyroptosis[J]. Experimental cell research, 2020, 389(1): 111847.
[7] Tao H, Zhao H, Mo A, et al. VX-765 attenuates silica-induced lung inflammatory injury and fibrosis by modulating alveolar macrophages pyroptosis in mice[J]. Ecotoxicology and Environmental Safety, 2023, 249: 114359.
[8] Wen S, Deng F, Li L, et al. VX‐765 ameliorates renal injury and fibrosis in diabetes by regulating caspase‐1‐mediated pyroptosis and inflammation[J]. Journal of Diabetes Investigation, 2022, 13(1): 22-33.
| Cell experiment [1]: | |
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Cell lines |
Caco-2 cells |
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Preparation Method |
Caco-2 cells were cultivated in DMEM medium supplemented with 10% heat-inactivated fetal bovine serum (FBS), 1% non-essential amino acids, and 1% glutamine at 37°C in an incubator with 5% CO2. Glucose-free DMEM was kept overnight in a hypoxia chamber (<0.5% O2 and 2.0% CO2). The cells were cultured in hypoxic conditions for 12h, and then removed from the hypoxia chamber. Thereafter, the cells were grown in the culture medium for 1h. The cells were divided into the following 3 groups: (1) Control group (cells cultured in DMEM in an incubator at 37°C with 21% O2 and 5% CO2); (2) H/R group (cells cultured in an incubator at 37°C with 1% O2 and 5% CO2 for 12h in hypoxia and 6h in reoxygenation); (3) H/R + VX-765 (5μM) group (cells pretreated with 5μM VX-765 for 24h and then subjected to hypoxia/reoxygenation). The levels of ROS and inflammatory factors in the cells were analyzed. |
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Reaction Conditions |
5μM; 24h |
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Applications |
VX-765 treatment reduced levels of ROS, TNF-α, IL-6, and IL-1β in Caco-2 cells exposed to H/R. |
| Animal experiment [2]: | |
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Animal models |
Male CD1 (ICR) mice |
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Preparation Method |
Male CD1 (ICR) mice (8 weeks old) were maintained in a controlled environment at 22±3°C and 60% relative humidity under a 12h light/dark cycle, and were given free access to standard rodent nutrition and water. Mice were injected intraperitoneally with 55mg/kg streptozotocin (STZ) or 0.1M citrate buffer (vehicle) for 5 days. 14 days after injection, mice with blood glucose level over 300mg/dl were considered diabetic. diabetic mice were administered intraperitoneally with 100mg/kg VX-765 daily, or vehicle for 8 weeks. The treatment with VX-765 was initiated 2 weeks after STZ injection. Kidneys of mice were collected for analysis. |
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Dosage form |
100mg/kg/day; 8 weeks; i.p. |
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Applications |
VX-765 treatment ameliorated renal inflammation and fibrosis in diabetic mice. |
References: [1] Sun Z, Gu L, Wu K E, et al. VX‐765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke‐induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway[J]. CNS neuroscience & therapeutics, 2020, 26(9): 952-961. [2] Wen S, Deng F, Li L, et al. VX‐765 ameliorates renal injury and fibrosis in diabetes by regulating caspase‐1‐mediated pyroptosis and inflammation[J]. Journal of Diabetes Investigation, 2022, 13(1): 22-33. | |
| Cas No. | 273404-37-8 | SDF | |
| المرادفات | Belnacasan; VX-765 | ||
| Chemical 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 | ||
| Canonical SMILES | CCOC1C(CC(=O)O1)NC(=O)C2CCCN2C(=O)C(C(C)(C)C)NC(=O)C3=CC(=C(C=C3)N)Cl | ||
| Formula | C24H33ClN4O6 | M.Wt | 508.99 |
| الذوبان | ≥ 313 mg/mL in DMSO, ≥ 50.5 mg/mL in EtOH with ultrasonic | Storage | Desiccate at -20°C |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9647 mL | 9.8234 mL | 19.6468 mL |
| 5 mM | 392.9 μL | 1.9647 mL | 3.9294 mL |
| 10 mM | 196.5 μL | 982.3 μL | 1.9647 mL |
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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 addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Related Biological Data
Inhibition of caspase 1 attenuates liver IRI mediated by GSDMD in macrophages. (a) The levels of caspase 1, cleaved-caspase 1, GSDMD, and GSDMD-N in each group were measured by Western blotting.(b)–(e) Relative expression of caspase 1, cleaved-caspase 1, GSDMD, and GSDMD-N in each group.
VX-765 (50 mg/kg) (GlpBio, USA) was administered intraperitoneally 1 h before liver IRI.
Oxid Med Cell Longev 2022 (2022). PMID: 36035360 IF: 6.543 -
Related Biological Data
The effects of belnacasan on cell viability, migration and invasion. (A–C) T98G, LN-18 and HEB cells were treated with different concentrations of belnacasan for 48 hours, and then CCK-8 assays were performed to determine the cell viability.
Cells were incubated in 96-well plates treated with the indicated concentrations (0 μM, 5 μM, 10 μM, 20 μM and 40 μM) of belnacasan (GLPBIO) for 48 hours.
Frontiers in Oncology 12 (2022): 717926. PMID: 35433410 IF: 4.7003 -
Related Biological Data
NLRP3 inflammasome activation by S. aureus is essential for the generation of GSDMD-N and the release of IL-1β and IL-18. A Activated caspase-1 and B GSDMD-N or released C IL-1β and D IL-18 of MAC-T cells treated with or without NLRP3 inhibitor MCC950 or caspase-1 inhibitor VX765 for 1.5 h prior to treatment with S. aureus for 4 h.
IL-18 of MAC-T cells treated with or without NLRP3 inhibitor MCC950 or caspase-1 inhibitor VX765 (Glpbio) for 1.5 h prior to treatment with S. aureus for 4 h.
Veterinary Research 53.1 (2022): 10. PMID: 35123552 IF: 4.3997
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