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Chemical Structure| 273404-37-8 Chemical Structure| 273404-37-8

Structure of VX-765
CAS No.: 273404-37-8

Chemical Structure| 273404-37-8

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Belnacasan (VX-765) is an orally bioactive proagent of VRT-043198, a potent and selective inhibitor of IL-converting enzyme (ICE)/caspase-1 with Kis of 0.8 nM and less than 0.6 nM for caspase-1 and caspase-4, respectively. It inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC50 of ~0.7 μM.

Synonyms: Belnacasan

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Product Details of VX-765

CAS No. :273404-37-8
Formula : C24H33ClN4O6
M.W : 509.00
SMILES Code : O=C([C@H]1N(C([C@@H](NC(C2=CC=C(N)C(Cl)=C2)=O)C(C)(C)C)=O)CCC1)N[C@@H](C3)[C@H](OCC)OC3=O
Synonyms :
Belnacasan
MDL No. :MFCD23102811
InChI Key :SJDDOCKBXFJEJB-MOKWFATOSA-N
Pubchem ID :11398092

Safety of VX-765

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of VX-765

pyroptosis

Isoform Comparison

Biological Activity

Target
  • Caspase-4

    Caspase-4, Ki:<0.6 nM

  • Caspase-1

    Caspase-1, Ki:0.8 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
neural progenitor cells 10 μM 2 h To evaluate the effect of VX-765 on mitochondrial respiration in neural progenitor cells, results showed that the oxygen consumption rate (OCR) was significantly reduced in the VX-765 treated group PMC11425199
PC12 cells 50 μM 24 h VX-765 pretreatment inhibited ketamine-induced pyroptosis in PC12 cells, reducing LDH release and levels of inflammatory cytokines (IL-1β and IL-18). PMC8527745
HAPI cells 10 μM 24 h VX-765 pretreatment significantly reduced ketamine-induced pyroptosis in HAPI cells, decreasing LDH release and levels of inflammatory cytokines (IL-1β and IL-18). PMC8527745
BMSCs-derived beige adipocytes 10 μM 24 h To investigate the effect of VX-765 on the thermogenic capacity of beige adipocytes, results showed that VX-765 treatment reduced the expression of UCP1, P-PKA, and P-HSL PMC10933663
BMDMs 20 µM 12 h Inhibited non-canonical inflammasome activation PMC6949489
HK2 cells 20 µg/ml 30 min To inhibit caspase-1 and its related pyroptosis PMC9830505

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Neonatal rats Ketamine-induced neurotoxicity model Intraperitoneal injection 25 mg/kg Every 90 minutes, 5 doses VX-765 pretreatment alleviated ketamine-induced hippocampal neuronal loss and improved cognitive dysfunction in neonatal rats. PMC8527745
Mice MC903-induced AD model Oral 50 mg/kg Once daily for 7 days To evaluate the effect of VX-765 on IL-33 expression and secretion in the MC903-induced AD model, results showed that VX-765 had no significant effect on IL-33 secretion PMC8463682
Mice HFD-induced obesity model Intraperitoneal injection 5 mg/kg Every other day for 2 weeks To investigate the effect of VX-765 on HFD-induced obese mice, results showed that VX-765 treatment alleviated obesity and metabolic disorders PMC10933663
Mice DSS-induced colitis model Intraperitoneal injection 20 mg/kg Once daily for 6 days VX-765 significantly reduced mortality, loss, and clinical scores in mice with colitis, and decreased the production of inflammatory cytokines IL-1β and IL-6 in colonic tissues. PMC6949489
Mice 70% partial hepatectomy model Oral 100 mg/kg Single dose, 4 hours before surgery To investigate the effect of VX-765 on liver regeneration, results showed that VX-765 had no effect on the cleavage of GSDMD PMC9426395

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00205465 Psoriasis PHASE2 COMPLETED 2025-09-05 -
NCT01048255 Partial Epilepsy PHASE2 COMPLETED 2025-11-10 Arkansas, Little Rock, Arkansa... More >>s, United States|California, Newport Beach, California, United States|Florida, Miami, Florida, United States|Florida, Sarasota, Florida, United States|Illinois, Chicago, Illinois, United States|Maryland, Baltimore, Maryland, United States|Maryland, Bethesda, Maryland, United States|Missouri, Chesterfield, Missouri, United States|New Jersey, Hackensack, New Jersey, United States|New York, New York, New York, United States|Pennsylvania, Philidelphia, Pennsylvania, United States|Virginia, Charlottesville, Virginia, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.96mL

0.39mL

0.20mL

9.82mL

1.96mL

0.98mL

19.65mL

3.93mL

1.96mL

References

 

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