Ceramidase (EC 3.5.1.23, acylsphingosine deacylase, glycosphingolipid ceramide deacylase) is an enzyme which cleaves fatty acids from ceramide, producing sphingosine (SPH) which in turn is phosphorylated by a sphingosine kinase to form sphingosine-1-phosphate (S1P).
[1] Ceramide, SPH, and S1P are bioactive lipids that mediate cell proliferation, differentiation, apoptosis, adhesion, and migration.
Presently, 7 human ceramidases encoded by 7 distinct genes have been cloned:[1] A deficiency in ASAH1 is associated with Farber disease.
Inhibitors of nCDase were identified via a high-throughput screening effort of large chemical libraries at Scripps Research.
Multiple rounds of chemical optimization ensued with improved potency in terms of IC50 and selectivity over counterscreen assays.