CZL80, a blood-brain barrier-penetrating caspase-1 inhibitor with IC50 of 0.01 μM, can be used to study the seizure susceptibility of febrile seizures and late potentiation.

Physicochemical Properties

Molecular Formula	C19H14N2O4S
Molecular Weight	366.39
CAS #	313482-91-6
Appearance	White to light yellow solid powder
SMILES	C(O)(=O)C1=CC=CC(NC(=O)C2=CC=CC(NC(C3SC=CC=3)=O)=C2)=C1
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Caspase-1 0.01 μM (IC50)
ln Vivo	CZL80 (7.5 mg/kg, iv, qod) significantly reduced neuronal excitability and the incidence of febrile seizures and, in adult mice, alleviated late-potentiation seizure susceptibility[1]. Delayed administration of CZL80 can effectively alleviate the progressive neurological dysfunction caused by photothrombosis[1].
Animal Protocol	Animal/Disease Models: Male C57BL/6 mice and Caspase-1 gene knockout (Caspase-1−/−) mice weighing 23-26 g (9-10 weeks old)[2]. Doses: 10, 30 mg/kg/d, 7 days. Route of Administration: i.p. Experimental Results: Rescued motor dysfunction after photothrombotic stroke in mice. Animal/Disease Models: Mice pups of caspase-1 knockout (Casp1−/−, RRID:IMSR_JAX:004947) and littermate controls (wild-type [WT], Casp1+/+)[1]. Doses: 0.0075, 0.075, 0.75 and 7.5 mg/kg (2% DMSO in saline), qod (every other day). Route of Administration: Intravenously injected. Experimental Results: Reduced seizure incidence, prolonged seizure latency and increased threshold to FS generation in a dose-dependent manner.
References	[1]. Structure-based discovery of CZL80, a caspase-1 inhibitor with therapeutic potential for febrile seizures and later enhanced epileptogenic susceptibility. Br J Pharmacol. 2020 Aug;177(15):3519-3534. [2]. Novel Caspase-1 inhibitor CZL80 improves neurological function in mice after progressive ischemic stroke within a long therapeutic time-window. Acta Pharmacol Sin. 2022 Nov;43(11):2817-2827.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 200 mg/mL (~545.87 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (13.65 mM)(saturation unknown) in 10% DMSO 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution and add it to 900 μL corn oil and mix well.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7293 mL	13.6467 mL	27.2933 mL
	5 mM	0.5459 mL	2.7293 mL	5.4587 mL
	10 mM	0.2729 mL	1.3647 mL	2.7293 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.