Belnacasan

Caspase 1 Inhibitor (peptidomimetic)Rx: ResearchCompound: Investigational

Also known as: ICE inhibitor VX-765, VRT-043198, VX-765

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Summary

Belnacasan (VX-765) is an orally bioavailable prodrug that is converted in vivo to its active metabolite VRT-043198, a potent and selective caspase-1 inhibitor. It was investigated primarily for epilepsy and inflammatory conditions. Clinical development was discontinued after Phase II trials did not meet primary endpoints.

Mechanism of Action

Selective, reversible inhibitor of caspase-1 (interleukin-1 beta converting enzyme, ICE), blocking the proteolytic cleavage and maturation of pro-IL-1β and pro-IL-18, thereby reducing downstream inflammatory signaling.

Routes of Administration

Oral

Goals & Uses

  • Inhibition of IL-1β-driven inflammationInflammationModerate
  • NeuroprotectionNeurologyLow
  • Reduction of seizure frequency in epilepsyNeurologyModerate
  • Treatment of inflammatory/autoimmune conditionsImmunologyLow

Contraindications

  • Severe hepatic impairmentOrganModerateLiver function concerns
  • Hypersensitivity to belnacasan or excipientsAllergyHigh

Adverse Effects

  • HeadacheNeurologicCommonPain in the head or upper neck
  • NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
  • Increased infection susceptibilityImmunologicalRare
  • Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers
  • DizzinessNeurologicUncommonFeeling faint, lightheaded, or unsteady

Drug Interactions

  • Antiepileptic drugs (e.g., valproate, carbamazepine)Low
  • CYP3A4 inhibitors (e.g., ketoconazole)Moderate
  • ImmunosuppressantsModeratePotential interaction with immune pathways or infection risk

Population Constraints

  • Pediatric patientsAgeRelative
  • Immunocompromised patientsImmunologicRelative
  • Pregnant womenReproductiveRelative

Regulatory Status

  • European UnionInvestigationalClinical trials conducted in EU jurisdictions; no EMA approval granted.
  • United StatesInvestigationalIND granted for clinical trials; never received FDA approval. Development discontinued post Phase II.
  • United KingdomInvestigationalNo MHRA approval; investigational use only.

Belnacasan was never approved by any major regulatory agency. Phase II trials in epilepsy were conducted but the program was discontinued. It remains a research tool compound.

Evidence & Sources

No sources recorded yet.

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