CZL80 is a brain-penetrable caspase-1 inhibitor with an IC50 of 0.01 μM, potentially applicable for studying febrile seizures and subsequent increased epileptogenic susceptibility [1].

Caspase-1:0.01 μM

CZL80 (7.5 mg/kg, i.v., qod) significantly reduced neuronal excitability and the incidence of febrile seizures, and in adult mice, it decreased the subsequent increased susceptibility to epilepsy [1]. Delayed administration of CZL80 effectively mitigated progressive neurological dysfunction caused by photothrombosis [1]. In male C57BL/6 mice and Caspase-1 knockout (Caspase-1 −/−) mice weighing 23-26 g (9-10 weeks old) [2], a dosage of 10, 30 mg/kg/d administered intraperitoneally for 7 days improved motor dysfunction after photothrombotic stroke. In mice pups of caspase-1 knockout (Casp1 −/−, RRID:IMSR_JAX:004947) and littermate controls (wild-type [WT], Casp1 +/+), with doses of 0.0075, 0.075, 0.75, and 7.5 mg/kg (2% DMSO in saline), administered intravenously every other day, CZL80 reduced seizure incidence, prolonged seizure latency, and increased the threshold for FS generation in a dose-dependent manner.