Structure-based discovery of CZL80, a caspase-1 inhibitor with therapeutic potential for febrile seizures and later enhanced epileptogenic susceptibility.

ABSTRACT:

Background and purpose

Febrile seizures (FS), the most common seizures in childhood and often accompanied by later epileptogenesis, are not well controlled. Inflammatory processes have been implicated in the pathophysiology of epilepsy. However, whether caspase-1 is involved in FS generation and could be a target for the treatment of FS is still unclear.

Experimental approach

By using pharmacological and gene intervention methods in C57BL/6J mice, we assessed the role of caspase-1 in FS generation. We used structural virtual screening against the active site of caspase-1, to screen compounds for druggable and safe low MW inhibitors of caspase-1 in vitro. One compound was chosen to test in vivo for therapeutic potential, using FS models in neonatal mice and epileptogenesis in

SUBMITTER: Tang Y 

PROVIDER: S-EPMC7348094 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature