Use of pyrimidinotriazinedione derivatives for the preparation of a medicament for inhibiting the activity of the human protease caspase-1
By efficiently binding pyrimidine triazine dione derivatives I and II to caspase-1, the toxicity and stability issues of existing inhibitors were resolved, achieving highly efficient inhibition of caspase-1, reducing IL-1β release and lung tissue damage, and demonstrating dual anti-inflammatory and organ-protective effects.
Patent Information
- Application Number
- CN202511136562.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-14
- Publication Date
- 2026-06-26
- Estimated Expiration
- 2045-08-14
AI Technical Summary
Existing caspase-1 inhibitors, such as VX-765, have hepatotoxicity issues, while Ac-YVAD-CMK has poor stability and low bioavailability, making it difficult to effectively inhibit caspase-1 activity and reduce inflammatory responses.
By using pyrimidine triazine dione derivatives I and II, the activity of caspase-1 was significantly inhibited by binding with high affinity, blocking its activation pathway, reducing IL-1β release, and penetrating the cell membrane for targeted delivery.
It effectively inhibits caspase-1 enzyme activity at nanomolar concentrations, exhibiting fast binding and slow dissociation kinetics, significantly reducing IL-1β release and lung tissue pathological damage, and providing dual anti-inflammatory and organ-protective effects.